Search results for: drug target

Authors: Deepak Kakde, Steve Howdle, Derek Irvine, Cameron Alexander

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The poor aqueous solubility is one of the major obstacles in the formulation development of many drugs. Around 70% of drugs are poorly soluble in aqueous media. In the last few decades, micelles have emerged as one of the major tools for solubilization of hydrophobic drugs. Micelles are nanosized structures (10-100nm) obtained by self-assembly of amphiphilic molecules into the water. The hydrophobic part of the micelle forms core which is surrounded by a hydrophilic outer shell called corona. These core-shell structures have been used as a drug delivery vehicle for many years. Although, the utility of micelles have been reduced due to the lack of sustainable materials. In the present study, a novel methoxy poly(ethylene glycol)-b-poly(ε-decalactone) (mPEG-b-PεDL) copolymer was synthesized by ring opening polymerization (ROP) of renewable ε-decalactone (ε-DL) monomers on methoxy poly(ethylene glycol) (mPEG) initiator using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a organocatalyst. All the reactions were conducted in bulk to avoid the use of toxic organic solvents. The copolymer was characterized by nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and differential scanning calorimetry (DSC).The mPEG-b-PεDL block copolymeric micelles containing indomethacin (IND) were prepared by nanoprecipitation method and evaluated as drug delivery vehicle. The size of the micelles was less than 40nm with narrow polydispersity pattern. TEM image showed uniform distribution of spherical micelles defined by clear surface boundary. The indomethacin loading was 7.4% for copolymer with molecular weight of 13000 and drug/polymer weight ratio of 4/50. The higher drug/polymer ratio decreased the drug loading. The drug release study in PBS (pH7.4) showed a sustained release of drug over a period of 24hr. In conclusion, we have developed a new sustainable polymeric material for IND delivery by combining the green synthetic approach with the use of renewable monomer for sustainable development of polymeric nanomedicine.

Keywords: dopolymer, ε-decalactone, indomethacin, micelles

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Authors: Saad Alkentar, Abdulkareem Assalem

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Recognizing small targets has always posed a significant challenge in image analysis. Over long distances, the image signal-to-noise ratio tends to be low, limiting the amount of useful information available to detection systems. Consequently, visual target recognition becomes an intricate task to tackle. In this study, we introduce a Track Before Detect (TBD) approach that leverages target trajectory information (coordinates) to effectively distinguish between noise and potential targets. By reframing the problem as a multivariate time series classification, we have achieved remarkable results. Specifically, our TBD method achieves an impressive 97% accuracy in separating target signals from noise within a mere half-second time span (consisting of 10 data points). Furthermore, when classifying the identified targets into our predefined categories—airplane, drone, and bird—we achieve an outstanding classification accuracy of 96% over a more extended period of 1.5 seconds (comprising 30 data points).

Keywords: small targets, drones, trajectory information, TBD, multivariate time series

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Authors: Chieh-Nan Chen, Ji-Yu Lin, I-Ming Chu

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Polypeptide thermosensitive hydrogel is an excellent candidate as a smart device to deliver drugs and cells due to its remarkable biocompatibility, low gelation concentration, and respond to temperature stimuli, it can be easily injected as a polymer solution into the patient’s body where it undergoes gelation due to an elevation in temperature. Poly (ethylene glycol) monomethyl ether-poly (ethyl-l-glutamate) (mPEG-PELG) contains a hydrophobic side chain –C2H5 which is useful in encapsulating and stabilizing hydrophobic drugs. In this study, we plan to focus on the hydrophobic anti-carcinogenic and anti-inflammatory drug curcumin, which due its insolubility in water, requires a proper carrier for delivery into the body. Our main concept is to use mPEG-PELG to stabilize curcumin, inject the curcumin-loaded hydrogel into the tumor site, and allow the enzymatically-sensitive hydrogel to be degraded by bodily fluids and release the drug. The polymers of interest have been successfully synthesized and characterized by 1H-NMR, FT-IR, SEM, and CMC. Curcumin loading content and drug release were assayed using HPLC. Preliminary results show that these materials have potential as a delivery vehicle for poorly soluble drugs.

Keywords: curcumin, drug release, hydrogel, polypeptide material

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Authors: Rodchares Hanrinth, Theerapong Srisil, Peeraya Sriphong, Pawich Paktipat

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The trigger tool is the low-cost, low-tech method to detect adverse events through clues called triggers. The Institute for Healthcare Improvement (IHI) has developed the Global Trigger Tool for measuring and preventing adverse events. However, this tool is not specific for detecting adverse drug events. The pharmacy-based trigger tool is needed to detect adverse drug events (ADEs). Group concept mapping is an effective method for conceptualizing various ideas from diverse stakeholders. This technique was used to identify a pharmacy-based trigger to detect adverse drug events (ADEs). The aim of this study was to involve the pharmacists in conceptualizing, developing, and prioritizing a feasible trigger tool to detect adverse drug events in a provincial hospital, the northeastern part of Thailand. The study was conducted during the 6-month period between April 1 and September 30, 2017. Study participants involved 20 pharmacists (17 hospital pharmacists and 3 pharmacy lecturers) engaging in three concept mapping workshops. In this meeting, the concept mapping technique created by Trochim, a highly constructed qualitative group technic for idea generating and sharing, was used to produce and construct participants' views on what triggers were potential to detect ADEs. During the workshops, participants (n = 20) were asked to individually rate the feasibility and potentiality of each trigger and to group them into relevant categories to enable multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the trigger list, cluster list, point map, point rating map, cluster map, and cluster rating map. The three workshops together resulted in 21 different triggers that were structured in a framework forming 5 clusters: drug allergy, drugs induced diseases, dosage adjustment in renal diseases, potassium concerning, and drug overdose. The first cluster is drug allergy such as the doctor’s orders for dexamethasone injection combined with chlorpheniramine injection. Later, the diagnosis of drug-induced hepatitis in a patient taking anti-tuberculosis drugs is one trigger in the ‘drugs induced diseases’ cluster. Then, for the third cluster, the doctor’s orders for enalapril combined with ibuprofen in a patient with chronic kidney disease is the example of a trigger. The doctor’s orders for digoxin in a patient with hypokalemia is a trigger in a cluster. Finally, the doctor’s orders for naloxone with narcotic overdose was classified as a trigger in a cluster. This study generated triggers that are similar to some of IHI Global trigger tool, especially in the medication module such as drug allergy and drug overdose. However, there are some specific aspects of this tool, including drug-induced diseases, dosage adjustment in renal diseases, and potassium concerning which do not contain in any trigger tools. The pharmacy-based trigger tool is suitable for pharmacists in hospitals to detect potential adverse drug events using clues of triggers.

Keywords: adverse drug events, concept mapping, hospital, pharmacy-based trigger tool

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Authors: Erna Judith Roach, Nalini Bhaskaranand

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Background & Significance: Asthma is the most common chronic disease among children. Education is the cornerstone of management of asthma to help the affected children. In India there are about 1.5- 3.0 million asthmatic children in the age group of 5-11 years. Many parents face management dilemmas in administration of medications to their children. Mothers being primary caregivers of children are often responsible for administering medications to them. The purpose of the study was to develop an educational package on techniques of drug administration for mothers of asthmatic children and determine its effectiveness in terms of improvement in skill in drug administration. Methodology: A quasi- experimental time series pre-test post -test control group design was used. Mothers of asthmatic children attending paediatric outpatient departments of selected hospitals along with their children between 5 and 12 years were included. Sample size consisted of 40 mothers in the experimental and 40 mothers in the control groups. Block randomization was used to assign samples to both the groups. The data collection instruments used were Baseline Proforma, Clinical Proforma, Daily asthma drug intake and symptoms diary and Observation Rating Scales on technique of using a metered dose inhaler with spacer; metered dose inhaler with facemask; metered dose inhaler alone and dry powder inhaler. The educational package consisted of a video and booklet on techniques of drug administration. Data were collected at baseline, 1, 3 and 6 months. Findings: The mean post-test scores in techniques of drug administration were higher than the mean pre-test scores in the experimental group in all techniques. The Friedman test (p < 0.01), Wilcoxon Signed Rank test (p < 0.008) and Mann Whitney U (p < 0.01) showed statistically significant difference in the experimental group than the control group. There was significant decrease in the average number of symptom days (11 Vs. 4 days/ month) and hospital visits (5 to 1 per month) in the experimental group when compared to the control group. Conclusion: The educational package was found to be effective in improving the skill of mothers in drug administration in all the techniques, especially with using the metered dose inhaler with spacer.

Keywords: childhood asthma, drug administration, mothers of children, inhaler

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Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Pravina Gurjar, Bothiraja Pour, Vijay Kumbhar, Ganesh Dama

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Andrographolide (AG), a bioactive phytoconstituent, has a wider range of pharmacological action. However, due to the intestinal degradation, shows low oral bioavailability. The aim of the present work was to develop Floating In-situ gelling Gastro retentive System (FISGS) for AG in order to enhance its site specific absorption and minimize pH dependent hydrolysis in alkaline environment. Further to increase its therapeutic efficacy for peptic ulcer disease caused by H. pyroli. Gellan based floating in situ gelling system of AG were prepared by using sodium citrate and calcium carbonate. The 32 factorial designs was used to study the effect of gellan and calcium carbonate concentration (independent variables) on dependent variable such as viscosity, floating lag time and drug release. Developed system was evaluated for drug content, floating lag time, viscosity, and drug release studies. Drug content, viscosity, and floating lag time was found to be 81-99%, 67-117 Cps, and 3-5 sec, respectively. The obtained system showed good in vitro floating ability for more than 12 h using 0.1 N HCl as dissolution medium with initial burst release followed by the controlled zero order drug release up to 24 hrs. In vivo testing of FISGS of AG to rats demonstrated significant antiulcer activity that were evaluated by various parameters like pH, volume, total acidity, millimole equivalent of H+ ions/30 min, and protein content of gastric content. The densities of all the formulation batches were found to be near about 0.9 and floating duration above 12 hr. It was observed that with the increase in conc. of gellan there was increase in the viscosity of formulation but all formulations were in optimum range. The drug content of optimized batch was found to be 99.23. In histopathology study of stomach, the villi at the mucosal surface, the intercellular junction, the intestinal lumen were intact; no destruction of the epithelium, and submucosal gland in formulation treated and control group animals as compared to pure drug AG and standard ranitidine. Gellan-based in situ gastro retentive floating system could be advantageous in terms of increased bioavailability of AG to maintain an effective drug conc. in gastric fluid as well as in serum for longer period of time.

Keywords: andrographolide, floating drug delivery, in situ gelling system, gastroretentive system

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Authors: Masoumeh Kazemi

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Depression is one of the most common mental disorders that damage mental health. In addition to mental distress, mental health damage affects other dimensions of human health, including physical and social health. According to the national study of diseases and injuries in Iran, the third health problem of the country is depression. The purpose of this study was to measure the level of depression in people referred to Karaj psychiatric treatment centers, and to investigate the relationship between depression and drug and alcohol consumption. The statistical population included 5000 people. Morgan table was used to determine the sample size. The research questions sought to identify the relationship between depression and factors such as drug and alcohol use, employment and marital status, and gender. Beck standard questionnaire was used to collect complete information. Cronbach's alpha coefficient was used to confirm the reliability of the questionnaire. To test research hypotheses, non-parametric methods of correlation coefficient, Spearman's rank, Mann-Whitney and Kruskal-Wallis tests were used. The results of using SPSS statistical software showed that there is a direct relationship between depression and drug and alcohol use. Also, the rate of depression was higher in women, widows and unemployed people. Finally, by conducting the present study, it is suggested that people use the following treatments in combination for effective recovery: 1. Cognitive Behavioral Therapy (CBT) 2. Interpersonal Therapy (IPT) 3. Treatment with appropriate medication 4. Special light therapy 5. Electric shock treatment (in acute and exceptional cases) 6. Self-help

Keywords: alcohol, depression, drug, Iran

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Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

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Authors: Mustafa Al Sukar, Azzam Sleit, Abdullatif Abu-Dalhoum, Bassam Al-Kasasbeh

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Use and abuse of drugs by teens is very common and can have dangerous consequences. The drugs contribute to physical and sexual aggression such as assault or rape. Some teenagers regularly use drugs to compensate for depression, anxiety or a lack of positive social skills. Teen resort to smoking should not be minimized because it can be "gateway drugs" for other drugs (marijuana, cocaine, hallucinogens, inhalants, and heroin). The combination of teenagers' curiosity, risk taking behavior, and social pressure make it very difficult to say no. This leads most teenagers to the questions: "Will it hurt to try once?" Nowadays, technological advances are changing our lives very rapidly and adding a lot of technologies that help us to track the risk of drug abuse such as smart phones, Wireless Sensor Networks (WSNs), Internet of Things (IoT), etc. This technique may help us to early discovery of drug abuse in order to prevent an aggravation of the influence of drugs on the abuser. In this paper, we have developed a Decision Support System (DSS) for detecting the drug abuse using Artificial Neural Network (ANN); we used a Multilayer Perceptron (MLP) feed-forward neural network in developing the system. The input layer includes 50 variables while the output layer contains one neuron which indicates whether the person is a drug addict. An iterative process is used to determine the number of hidden layers and the number of neurons in each one. We used multiple experiment models that have been completed with Log-Sigmoid transfer function. Particularly, 10-fold cross validation schemes are used to access the generalization of the proposed system. The experiment results have obtained 98.42% classification accuracy for correct diagnosis in our system. The data had been taken from 184 cases in Jordan according to a set of questions compiled from Specialists, and data have been obtained through the families of drug abusers.

Keywords: drug addiction, artificial neural networks, multilayer perceptron (MLP), decision support system

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Authors: Monika Patel, Kazuaki Matsumura

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Synthetic hydrogels, with their unique properties such as porosity, strength, and swelling in aqueous environment, are being used in many fields from food additives to regenerative medicines, from diagnostic and pharmaceuticals to drug delivery systems (DDS). But, hydrogels also have some limitations in terms of homogeneity of drug distribution and quantity of loaded drugs. As an alternate, polymeric micelles are extensively used as DDS. With the ease of self-assembly, and distinct stability they remarkably improve the solubility of hydrophobic drugs. However, presently, combinational therapy is the need of time and so are systems which are capable of releasing more than one drug. And it is one of the major challenges towards DDS to control the release of each drug independently, which simple DDS cannot meet. In this work, we present an amphiphilic polypeptide based micelle hydrogel composite to study the dual drug release for wound healing purposes using Amphotericin B (AmpB) and Curcumin as model drugs. Firstly, two differently charged amphiphilic polypeptide chains were prepared namely, poly L-Lysine-b-poly phenyl alanine (PLL-PPA) and poly Glutamic acid-b-poly phenyl alanine (PGA-PPA) through ring opening polymerization of amino acid N-carboxyanhydride. These polymers readily self-assemble to form micelles with hydrophobic PPA block as core and hydrophilic PLL/PGA as shell with an average diameter of about 280nm. The thus formed micelles were loaded with the model drugs. The PLL-PPA micelle was loaded with curcumin and PGA-PPA was loaded with AmpB by dialysis method. Drug loaded micelles showed a slight increase in the mean diameter and were fairly stable in solution and lyophilized forms. For forming the micelles hydrogel composite, the drug loaded micelles were dissolved and were cross linked using genipin. Genipin uses the free –NH2 groups in the PLL-PPA micelles to form a hydrogel network with free PGA-PPA micelles trapped in between the 3D scaffold formed. Different composites were tested by changing the weight ratios of the both micelles and were seen to alter its resulting surface charge from positive to negative with increase in PGA-PPA ratio. The composites with high surface charge showed a burst release of drug in initial phase, were as the composites with relatively low net charge showed a sustained release. Thus the resultant surface charge of the composite can be tuned to tune its drug release profile. Also, while studying the degree of cross linking among the PLL-PPA particles for effect on dual drug release, it was seen that as the degree of crosslinking increases, an increase in the tendency to burst release the drug (AmpB) is seen in PGA-PPA particle, were as on the contrary the PLL-PPA particles showed a slower release of Curcumin with increasing the cross linking density. Thus, two different pharmacokinetic profile of drugs were seen by changing the cross linking degree. In conclusion, a unique charged amphiphilic polypeptide based micelle hydrogel composite for dual drug delivery. This composite can be finely tuned on the basis of need of drug release profiles by changing simple parameters such as composition, cross linking and pH.

Keywords: amphiphilic polypeptide, dual drug release, micelle hydrogel composite, tunable DDS

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Authors: Nitin Jadhav, Pradeep R. Vavia

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Poor water soluble drugs are difficult to promote for oral drug delivery as they demonstrate poor and variable bioavailability because of its poor solubility and dissolution in GIT fluid. Nowadays lipid based formulations especially self microemulsifying drug delivery system (SMEDDS) is found as the most effective technique. With all the impressive advantages, the need of high amount of surfactant (50% - 80%) is the major drawback of SMEDDS. High concentration of synthetic surfactant is known for irritation in GIT and also interference with the function of intestinal transporters causes changes in drug absorption. Surfactant may also reduce drug activity and subsequently bioavailability due to the enhanced entrapment of drug in micelles. In chronic treatment these issues are very conspicuous due to the long exposure. In addition the liquid self microemulsifying system also suffers from stability issues. Recently one novel approach of solid stabilized micro and nano emulsion (Pickering emulsion) has very admirable properties such as high stability, absence or very less concentration of surfactant and easily converts into the dry form. So here we are exploring pickering dry emulsion system for dissolution enhancement of anti-lipemic, extremely poorly water soluble drug (Fenofibrate). Oil moiety for emulsion preparation was selected mainly on the basis of higher solubility of drug. Captex 300 was showed higher solubility for fenofibrate, hence selected as oil for emulsion. With Silica (solid stabilizer); Span 20 was selected to improve the wetting property of it. Emulsion formed by Silica and Span20 as stabilizer at the ratio 2.5:1 (silica: span 20) was found very stable at the particle size 410 nm. The prepared emulsion was further preceded for spray drying and formed microcapsule evaluated for in-vitro dissolution study, in-vivo pharmacodynamic study and characterized for DSC, XRD, FTIR, SEM, optical microscopy etc. The in vitro study exhibits significant dissolution enhancement of formulation (85 % in 45 minutes) as compared to plain drug (14 % in 45 minutes). In-vivo study (Triton based hyperlipidaemia model) exhibits significant reduction in triglyceride and cholesterol with formulation as compared to plain drug indicating increasing in fenofibrate bioavailability. DSC and XRD study exhibit loss of crystallinity of drug in microcapsule form. FTIR study exhibit chemical stability of fenofibrate. SEM and optical microscopy study exhibit spherical structure of globule coated with solid particles.

Keywords: captex 300, fenofibrate, pickering dry emulsion, silica, span20, stability, surfactant

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Authors: Pooja Kumari, Anandkumar Tengli

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Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: ShuHui Yang, ChingChing Lu

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Measuring event-related potentials (ERPs) has been fundamental to our understanding of how people process language. One specific ERP component, a P600, has been hypothesized to be associated with syntactic reanalysis processes. We, however, propose that the P600 is not restricted to reanalysis processes, but is the index of the structural pattern processing. To investigate the structural pattern processing, we utilized the effects of stimulus degradation in structural priming. To put it another way, there was no P600 effect if the structure of the prime was the same with the structure of the target. Otherwise, there would be a P600 effect if the structure were different between the prime and the target. In the experiment, twenty-two participants were presented with four sentences of Tang poetry. All of the first two sentences, being prime, were conducted with SVO+VP. The last two sentences, being the target, were divided into three types. Type one of the targets was SVO+VP. Type two of the targets was SVO+VPVP. Type three of the targets was VP+VP. The result showed that both of the targets, SVO+VPVP and VP+VP, elicited positive-going brainwave, a P600 effect, at 600~900ms time window. Furthermore, the P600 component was lager for the target’ VP+VP’ than the target’ SVO+VPVP’. That meant the more dissimilar the structure was, the lager the P600 effect we got. These results indicate that P600 was the index of the structure processing, and it would affect the P600 effect intensity with the degrees of structural heterogeneity.

Keywords: ERPs, P600, structural pattern, structural priming, Tang poetry

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Authors: Han Xiao

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The development of nanomedicines has recently achieved several breakthroughs in the field of cancer treatment; however, the biocompatibility and targeted burst release of these medications remain a limitation, which leads to serious side effects and significantly narrows the scope of their applications. The self-assembly of intermediate filament protein (IFP) peptides was triggered by a hydrophobic cation drug 7-amino actinomycin D (7-AAD) to synthesize pH-activatable nanoparticles (NPs) that could simultaneously locate tumors and produce antitumor effects. The designed IFP peptide included a target peptide (arginine–glycine–aspartate), a negatively charged region, and an α-helix sequence. It also possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. 7-AAD molecules with excellent near-infrared fluorescence properties could be target delivered into tumor cells by NPs and released immediately in the acidic environments of tumors and endosome/lysosomes, ultimately inducing cytotoxicity by arresting the tumor cell cycle with inserted DNA. It is noteworthy that the IFP/7-AAD NPs tail vein injection approach demonstrated not only high tumor-targeted imaging potential, but also strong antitumor therapeutic effects in vivo. The proposed strategy may be used in the delivery of cationic antitumor drugs for precise imaging and cancer therapy.

Keywords: 7-amino actinomycin D, intermediate filament protein, nanoparticle, tumor image

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Authors: P. S. Jain, K. D. Bobade, S. J. Surana

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A simple, selective, precise and Stability-indicating High-performance thin-layer chromatographic method for analysis of Naftopidil both in a bulk and in pharmaceutical formulation has been developed and validated. The method employed, HPTLC aluminium plates precoated with silica gel as the stationary phase. The solvent system consisted of hexane: ethyl acetate: glacial acetic acid (4:4:2 v/v). The system was found to give compact spot for Naftopidil (Rf value of 0.43±0.02). Densitometric analysis of Naftopidil was carried out in the absorbance mode at 253 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r2=0.999±0.0001 with respect to peak area in the concentration range 200-1200 ng per spot. The method was validated for precision, recovery and robustness. The limits of detection and quantification were 20.35 and 61.68 ng per spot, respectively. Naftopidil was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and thermal conditions. This indicates that the drug is susceptible to acid, base, oxidation and thermal conditions. The degraded product was well resolved from the pure drug with significantly different Rf value. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of investigated drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of Naftopidil in bulk drug and pharmaceutical formulation.

Keywords: naftopidil, HPTLC, validation, stability, degradation

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Authors: Indu Verma, Santanu Kumar Pal

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Interactions between DNA and adsorbed Poly (L-lysine) (PLL) on liquid crystal (LC) droplets were investigated using polarizing optical microcopy (POM) and epi-fluorescence microscopy. Earlier, we demonstrated that adsorption of PLL to the LC/aqueous interface resulted in homeotropic orientation of the LC and thus exhibited a radial configuration of the LC confined within the droplets. Subsequent adsorption of DNA (single stranded DNA/double stranded DNA) at PLL coated LC droplets was found to trigger a LC reorientation within the droplets leading to pre-radial/bipolar configuration of those droplets. To our surprise, subsequent exposure of complementary ssDNA (c-ssDNA) to ssDNA/ adsorbed PLL modified LC droplets did not cause the LC reorientation. This is likely due to the formation of polyplexes (DNA-PLL complex) as confirmed by fluorescence microscopy and atomic force microscopy. In addition, dsDNA adsorbed PLL droplets have been found to be effectively used to displace (controlled release) propidium iodide (a model drug) encapsulated within dsDNA over time. These observations suggest the potential for a label free droplet based LC detection system that can respond to DNA and may provide a simple method to develop DNA-based drug nano-carriers.

Keywords: DNA biosensor, drug delivery, interfaces, liquid crystal droplets

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Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

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Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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Authors: Vipin Saini, Sunil Kamboj, Suman Bala, A. Pandurangan

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The present research is aimed at fabrication of multiple-unit controlled-release tablet formulation of aceclofenac by employing acrylic polymers as the release controlling excipients for drug multi-particulates to achieve the desired objectives of maintaining the same controlled release characteristics as that prior to their compression into tablet. Various manufacturers are successfully manufacturing and marketing aceclofenac controlled release tablet by applying directly coating materials on the tablet. The basic idea behind development of such formulations was to employ aqueous acrylics polymers dispersion as an alternative to the existing approaches, wherein the forces of compression may cause twist of drug pellets, but do not have adverse effects on the drug release properties. Thus, the study was undertaken to illustrate manufacturing of controlled release aceclofenac multiple-unit tablet formulation.

Keywords: aceclofenac, multiple-unit tablets, acrylic polymers, controlled-release

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Authors: Nizar Jawad Hadi, Sajad Abd Alabbas

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Because of their ability to encapsulate and release drugs in a controlled manner, microspheres fabricated from polymer emulsions using microfluidic devices have shown promise for drug delivery applications. In this study, the effects of velocity, density, viscosity, and surface tension, as well as channel diameter, on microsphere generation were investigated using Fluent Ansys software. The software was programmed with the physical properties of the polymer emulsion such as density, viscosity and surface tension. Simulation will then be performed to predict fluid flow and microsphere production and improve the design of drug delivery applications based on changes in these parameters. The effects of capillary and Weber numbers are also studied. The results of the study showed that the size of the microspheres can be controlled by adjusting the speed and diameter of the channel. Narrower microspheres resulted from narrower channel widths and higher flow rates, which could improve drug delivery efficiency, while smaller microspheres resulted from lower interfacial surface tension. The viscosity and density of the polymer emulsion significantly affected the size of the microspheres, ith higher viscosities and densities producing smaller microspheres. The loading and drug release properties of the microspheres created with the microfluidic technique were also predicted. The results showed that the microspheres can efficiently encapsulate drugs and release them in a controlled manner over a period of time. This is due to the high surface area to volume ratio of the microspheres, which allows for efficient drug diffusion. The ability to tune the manufacturing process using factors such as speed, density, viscosity, channel diameter, and surface tension offers a potential opportunity to design drug delivery systems with greater efficiency and fewer side effects.

Keywords: polymer emulsion, microspheres, numerical simulation, microfluidic device

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Authors: Flavia Laffleur

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Summary: Biomaterials have gained immense interest in the pharmaceutical research in the last decades. Hyaluronic acid a carbohydrate and mucopolysaccharide was chemically modified in order to achieve and establish a promising platform for buccal drug delivery. Aim: Novel biomaterial was tested for its potential for buccal drug delivery. Background: Polysaccharide hyaluronic acid (HA) was chemically modified with cysteine ethyl ether (CYS). By immobilization of the thiol-bearing ligand on the polymeric backbone the thiolated bioconjugate HA-CYS was obtained. Methodology: Mucoadhesive, permeation enhancing and stability potential as well as mechanical, physicochemical properties further mucoadhesive strength, swelling index and residence time were investigated. The developed thiolated bioconjugate displayed enhanced mucoadhesiveness on buccal mucosa as well as permeation behavior and polymer stability. The near neutral pH and negative cytotoxicity studies indicated their non-irritability and biocompatible nature with biological tissues. Further, the model drug sulforhodamine 101 was incorporated to determine its drug release profiles. Results: The synthesized thiomer showed no toxicity. The mucoadhesion of thiolated hyaluronic acid on buccal mucosa was significantly improved in comparison to unmodified one. The biomaterial showed 2.5-fold higher stability in polymer structure. The release of sulforhodamine in the presence of thiolated hyaluronic acid was 2.3-fold increased compared to hyaluronic acid. Conclusion: Thus, the promising results encourage further investigations and exploitation of this versatile polysaccharide. So far, hyaluronic acid was not evaluated for buccal drug delivery.

Keywords: buccal delivery, hyaluronic acid, mucoadhesion, thiomers

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Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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Authors: Atinderpal Kaur, Shweta Dang

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Our aim is to develop a nanoemulsion-based delivery system containing polyphenon 60 (P60) and ciprofloxacin (Cipro) for intravaginal delivery to treat urinary tract infection. In the present study Polyphenon 60 (P60) and ciprofloxacin (Cipro) were loaded in a single nano emulsion (NE) system via ultra-sonication technique and characterized for particle size, in vitro release and antibacterial efficacy against Bcl-2 level Escherichia coli bacteria. To determine in vivo pharmacokinetic parameters and intravaginal transportation of NE, gamma scintigraphy and biodistribution study was conducted by radiolabelling NE with technetium pertechnetate (99mTc). The preliminary antibacterial investigation showed synergy between these compounds with FICindex of 0.42. The developed formulation showed zeta potential +55.3 and particle size of 151.7 nm, with PDI of 0.196. The in vitro release percentage of P60 at the end of 7th hours was 94.8 ± 0.9 % whereas the release for Cipro was 75.1± 0.15 % in simulated vaginal media. MBC was identified and the findings demonstrated that in both ESBL (Extended Spectrum β- lactamase) and MBL (Metallo β- lactamase) cultures the P60+Cipro NE showed inhibition of growth of all the isolates at 2 mg/ml dilutions. The percentage per gram of radiolabelled drug was found (3.50±0.26) and (3.81±0.30) in kidney and urinary bladder, respectively at 3 h. From the findings, it was concluded that the developed P60+Cipro NE was transported efficiently throughout the target organs, had long duration of action and high biocompatibility via intravaginal administration as compared to oral administration.

Keywords: ciprofloxacin, gamma scintigraphy, intravaginal drug delivery, Polyphenon 60

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Authors: Salvana P. M. Costa, Tarcyla A. Gomes, Giovanna C. R. M. Schver, Leslie R. M. Ferraz, Cristovão R. Silva, Magaly A. M. Lyra, Danilo A. F. Fonte, Larissa A. Rolim, Amanda C. Q. M. Vieira, Miracy M. Albuquerque, Pedro J. Rolim-neto

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Efavirenz (EFV) is considered one of the most widely used anti-HIV drugs. However, it is classified as a drug class II (poorly soluble, highly permeable) according to the biopharmaceutical classification system, presenting problems of absorption in the gastrointestinal tract and thereby inadequate bioavailability for its therapeutic action. This study aimed to overcome these barriers by developing and obtaining solid dispersions (SD) in order to increase the EFZ bioavailability. For the development of SD with EFV, theoretical and practical studies were initially performed. Thus, there was a choice of a carrier to be used. For this, it was analyzed the various criteria such as glass transition temperature of the polymer, intra- and intermolecular interactions of hydrogen bonds between drug and polymer, the miscibility between the polymer and EFV. The choice of the obtainment method of the SD came from the analysis of which method is the most consolidated in both industry and literature. Subsequently, the choice of drug and carrier concentrations in the dispersions was carried out. In order to obtain DS to present the drug in its amorphous form, as the DS were obtained, they were analyzed by X-ray diffraction (XRD). SD are more stable the higher the amount of polymer present in the formulation. With this assumption, a SD containing 10% of drug was initially prepared and then this proportion was increased until the XRD showed the presence of EFV in its crystalline form. From this point, it was not produced SD with a higher concentration of drug. Thus, it was allowed to select PVP-K30, PVPVA 64 and the SOLUPLUS formulation as carriers, once it was possible the formation of hydrogen bond between EFV and polymers since these have hydrogen acceptor groups capable of interacting with the donor group of the drug hydrogen. It is worth mentioning also that the films obtained, independent of concentration used, were presented homogeneous and transparent. Thus, it can be said that the EFV is miscible in the three polymers used in the study. The SD and Physical Mixtures (PM) with these polymers were prepared by the solvent method. The EFV diffraction profile showed main peaks at around 2θ of 6,24°, in addition to other minor peaks at 14,34°, 17,08°, 20,3°, 21,36° and 25,06°, evidencing its crystalline character. Furthermore, the polymers showed amorphous nature, as evidenced by the absence of peaks in their XRD patterns. The XRD patterns showed the PM overlapping profile of the drug with the polymer, indicating the presence of EFV in its crystalline form. Regardless the proportion of drug used in SD, all the samples showed the same characteristics with no diffraction peaks EFV, demonstrating the behavior amorphous products. Thus, the polymers enabled, effectively, the formation of amorphous SD, probably due to the potential hydrogen bonds between them and the drug. Moreover, the XRD analysis showed that the polymers were able to maintain its amorphous form in a concentration of up to 80% drug.

Keywords: amorphous form, Efavirenz, solid dispersions, solubility

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Authors: Rizalyn Gonzales, Harold Monteclaro

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This study determined the effects of net height on the capture performance of crab entangling nets. Fishing trials were conducted using nets with the following net heights: 1) 12 meshes down (MD), 2) 24 MD and 3) 50 MD. A total of 1,290 individuals comprising of 87 species belonging to 53 families were caught. One-way ANOVA showed that net height significantly affects various catch parameters such as catch per unit effort (CPUE) of the total and target catch, amount of non-target catch, sizes and species richness. The use of appropriate net height is a potential technical measure for a selective but still efficient crab entangling net fishery. Lower net height significantly reduced non-target catch up to 70%. While lower nets decreased the CPUE of target catch such as blue swimming crab Portunus pelagicus and christian crab Charybdis feriatus up to 65% in 12 MD, catch in 24 MD was not significantly different with that in 50 MD. The use of 24 MD also resulted in capturing larger-sized Portunus pelagicus. Catch species richness decreased up to 58% in lower nets. These results are useful to fisheries managers and government institutions to develop or improve existing regulations towards a sustainable crab fishery particularly blue swimming crabs.

Keywords: blue swimming crabs, catch per unit effort, crab entangling nets, net height

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Authors: Muhammad Imran Din

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The aim of this study was to understand the interaction between multi-walled carbon nano tubes (MCNTs) and anticancer agents and evaluate the drug-loading ability of MCNTs. Batch adsorption experiments were carried out for adsorption of 5-Fluorouracil (5-FL) using MCNTs. The effect of various operating variables, viz., adsorbent dosage, pH, contact time and temperature for adsorption of 5-Fluorouracil (5-FL) has been studied. The Freundlich adsorption model was successfully employed to describe the adsorption process. It was found that the pseudo-second-order mechanism is predominant and the overall rate of the 5-Fluorouracil (5-FL) adsorption process appears to be controlled by the more than one-step. Thermodynamic parameters such as free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°) have been calculated respectively, revealed the spontaneous, endothermic and feasible nature of adsorption process. The results showed that carbon nano tubes were able to form supra molecular complexes with 5-Fluorouracil (5-FL) by π-π stacking and possessed favorable loading properties as drug carriers.

Keywords: drug, adsorption, anticancer, 5-Fluorouracil (5-FL)

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Authors: Shraddha Acharya, Sharad Kumar Sharma, Ratna Bhattarai, Bhagwan Maharjan, Deepak Dahal, Serpahine Kaminsa

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Background: Drug-resistant (DR) tuberculosis (TB) continues to be a threat in Nepal, with an estimated 2800 new cases every year. The treatment of DR-TB with second line TB drugs is complex and takes longer time with comparatively lower treatment success rate than drug-susceptible TB. Delay in treatment initiation for DR-TB patients might further result in unfavorable treatment outcomes and increased transmission. This study thus aims to determine median time taken to initiate second-line treatment among Rifampicin Resistant (RR) diagnosed TB patients and to assess the proportion of treatment delays among various type of DR-TB cases. Method: A retrospective cohort study was done using national routine electronic data (DRTB and TB Laboratory Patient Tracking System-DHIS2) on drug resistant tuberculosis patients between January 2020 and December 2022. The time taken for treatment initiation was computed as– days from first diagnosis as RR TB through Xpert MTB/Rif test to enrollment on second-line treatment. The treatment delay (>7 days after diagnosis) was calculated. Results: Among total RR TB cases (N=954) diagnosed via Xpert nationwide, 61.4% were enrolled under shorter-treatment regimen (STR), 33.0% under longer treatment regimen (LTR), 5.1% for Pre-extensively drug resistant TB (Pre-XDR) and 0.4% for Extensively drug resistant TB (XDR) treatment. Among these cases, it was found that the median time from diagnosis to treatment initiation was 6 days (IQR:2-15.8). The median time was 5 days (IQR:2.0-13.3) among STR, 6 days (IQR:3.0-15.0) among LTR, 30 days (IQR:5.5-66.8) among Pre-XDR and 4 days (IQR:2.5-9.0) among XDR TB cases. The overall treatment delay (>7 days after diagnosis) was observed in 42.4% of the patients, among which, cases enrolled under Pre-XDR contributed substantially to treatment delay (72.0%), followed by LTR (43.6%), STR (39.1%) and XDR (33.3%). Conclusion: Timely diagnosis and prompt treatment initiation remain fundamental focus of the National TB program. The findings of the study, however suggest gaps in timeliness of treatment initiation for the drug-resistant TB patients, which could bring adverse treatment outcomes. Moreover, there is an alarming delay in second line treatment initiation for the Pre-XDR TB patients. Therefore, this study generates evidence to identify existing gaps in treatment initiation and highlights need for formulating specific policies and intervention in creating effective linkage between the RR TB diagnosis and enrollment on second line TB treatment with intensified efforts from health providers for follow-ups and expansion of more decentralized, adequate, and accessible diagnostic and treatment services for DR-TB, especially Pre-XDR TB cases, due to the observed long treatment delays.

Keywords: drug-resistant, tuberculosis, treatment initiation, Nepal, treatment delay

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Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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Authors: Salma E. Ahmed

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Since the mid 50’s, enormous attention has been paid towards nanocarriers and their applications in drug and gene delivery. Among these vesicles, liposomes and micelles have been heavily investigated due to their many advantages over other types. Liposomes, for instance, are mostly distinguished by their ability to encapsulate hydrophobic, hydrophilic and amphiphilic drugs. Micelles, on the other hand, are self-assembled shells of lipids, amphiphilic or oppositely charged block copolymers that, once exposed to aqueous media, can entrap hydrophobic agents, and possess prolonged circulation in the bloodstream. Both carriers are considered compatible and biodegradable. Nevertheless, they have limited stabilities, chemical versatilities, and drug encapsulation efficiencies. In order to overcome these downsides, strategies for optimizing a novel drug delivery system that has the architecture of liposomes and polymeric characteristics of micelles have been evolved. Polymersomes are vehicles with fluidic cores and hydrophobic shells that are protected and isolated from the aqueous media by the hydrated hydrophilic brushes which give the carrier its distinctive polymeric bilayer shape. Similar to liposomes, this merit enables the carrier to encapsulate a wide range of agents, despite their affinities and solubilities in water. Adding to this, the high molecular weight of the amphiphiles that build the body of the polymersomes increases their colloidal and chemical stabilities and reduces the permeability of the polymeric membranes, which makes the vesicles more protective to the encapsulated drug. These carriers can also be modified in ways that make them responsive when targeted or triggered, by manipulating their composition and attaching moieties and conjugates to the body of the carriers. These appealing characteristics, in addition to the ease of synthesis, gave the polymersomes greater potentials in the area of drug delivery. Thus, their design and characterization, in comparison with liposomes and micelles, are briefly reviewed in this work.

Keywords: controlled release, liposomes, micelles, polymersomes, targeting

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