Search results for: Drug delivery

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

Abstract:

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: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

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Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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Authors: Mostafa Mabrouk, Basma E. Abdel-Ghany, Mona Moaness, Bothaina M. Abdel-Hady, Hanan H. Beherei

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Tissue engineering became a promising field for bone repair and regenerative medicine in which cultured cells, scaffolds and osteogenic inductive signals are used to regenerate tissues. The annual cost of treating bone defects in Egypt has been estimated to be many billions, while enormous costs are spent on imported bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. The current study is aimed at developing a more strategic approach in order to speed-up recovery after bone damage. This will reduce the risk of fatal surgical complications and improve the quality of life of people affected with such fractures. 3D scaffolds loaded with cheap nano-particles that possess an osteogenic effect were prepared by nano-electrospinning. The Microstructure and morphology characterizations of the 3D scaffolds were monitored using scanning electron microscopy (SEM). The physicochemical characterization was investigated using X-ray diffractometry (XRD) and infrared spectroscopy (IR). The Physicomechanical properties of the 3D scaffold were determined by a universal testing machine. The in vitro bioactivity of the 3D scaffold was assessed in simulated body fluid (SBF). The bone-bonding ability of novel 3D scaffolds was also evaluated. The obtained nanofibrous scaffolds demonstrated promising microstructure, physicochemical and physicomechanical features appropriate for enhanced bone regeneration. Therefore, the utilized nanomaterials loaded with the drug are greatly recommended as cheap alternatives to growth factors.

Keywords: bone regeneration, cheap scaffolds, nanomaterials, active molecules

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Authors: Bhupendra G. Prajapati, Alpesh R. Patel

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The aim of this research work is to develop sustained release multi-particulates dosage form of Dexketoprofen trometamol, which is the pharmacologically active isomer of ketoprofen. The objective is to utilization of active enantiomer with minimal dose and administration frequency, extended release multi-particulates dosage form development for better patience compliance was explored. Drug loaded and sustained release coated pellets were prepared by fluidized bed coating principle by wurster coater. Microcrystalline cellulose as core pellets, povidone as binder and talc as anti-tacking agents were selected during drug loading while Kollicoat SR 30D as sustained release polymer, triethyl citrate as plasticizer and micronized talc as an anti-adherent were used in sustained release coating. Binder optimization trial in drug loading showed that there was increase in process efficiency with increase in the binder concentration. 5 and 7.5%w/w concentration of Povidone K30 with respect to drug amount gave more than 90% process efficiency while higher amount of rejects (agglomerates) were observed for drug layering trial batch taken with 7.5% binder. So for drug loading, optimum Povidone concentration was selected as 5% of drug substance quantity since this trial had good process feasibility and good adhesion of the drug onto the MCC pellets. 2% w/w concentration of talc with respect to total drug layering solid mass shows better anti-tacking property to remove unnecessary static charge as well as agglomeration generation during spraying process. Optimized drug loaded pellets were coated for sustained release coating from 16 to 28% w/w coating to get desired drug release profile and results suggested that 22% w/w coating weight gain is necessary to get the required drug release profile. Three critical process parameters of Wurster coating for sustained release were further statistically optimized for desired quality target product profile attributes like agglomerates formation, process efficiency, and drug release profile using central composite design (CCD) by Minitab software. Results show that derived design space consisting 1.0 to 1.2 bar atomization air pressure, 7.8 to 10.0 gm/min spray rate and 29-34°C product bed temperature gave pre-defined drug product quality attributes. Scanning Image microscopy study results were also dictate that optimized batch pellets had very narrow particle size distribution and smooth surface which were ideal properties for reproducible drug release profile. The study also focused on optimized dexketoprofen trometamol pellets formulation retain its quality attributes while administering with common vehicle, a liquid (water) or semisolid food (apple sauce). Conclusion: Sustained release multi-particulates were successfully developed for dexketoprofen trometamol which may be useful to improve acceptability and palatability of a dosage form for better patient compliance.

Keywords: dexketoprofen trometamol, pellets, fluid bed technology, central composite design

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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: Jie Gao

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The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Sanjay Kumar Behera, Kanhu Charan Patra

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A GIS-based method has been applied for the determination of soil erosion and sediment yield in a small watershed in Ong River basin, Odisha, India. The method involves spatial disintegration of the catchment into homogenous grid cells to capture the catchment heterogeneity. The gross soil erosion in each cell was calculated using Universal Soil Loss Equation (USLE) by carefully determining its various parameters. The concept of sediment delivery ratio is used to route surface erosion from each of the discretized cells to the catchment outlet. The process of sediment delivery from grid cells to the catchment outlet is represented by the topographical characteristics of the cells. The effect of DEM resolution on sediment yield is analyzed using two different resolutions of DEM. The spatial discretization of the catchment and derivation of the physical parameters related to erosion in the cell are performed through GIS techniques.

Keywords: DEM, GIS, sediment delivery ratio, sediment yield, soil erosion

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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: Abeer Amayri, Akif A. Bulgak

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Due to today’s globalization as well as outsourcing practices of the companies, the Supply Chain (SC) performances have become more dependent on the efficient movement of material among places that are geographically dispersed, where there is more chance for disruptions. One such disruption is the quality and delivery uncertainties of outsourcing. These uncertainties could lead the products to be unsafe and, as is the case in a number of recent examples, companies may have to end up in recalling their products. As a result of these problems, there is a need to develop a methodology for selecting suppliers globally in view of risks associated with low quality and late delivery. Accordingly, we developed a two-stage stochastic model that captures the risks associated with uncertainty in quality and delivery as well as a solution procedure for the model. The stochastic model developed simultaneously optimizes supplier selection and purchase quantities under price discounts over a time horizon. In particular, our target is the study of global organizations with multiple sites and multiple overseas suppliers, where the pricing is offered in suppliers’ local currencies. Our proposed methodology is applied to a case study for a US automotive company having two assembly plants and four potential global suppliers to illustrate how the proposed model works in practice.

Keywords: global supply chains, quality, stochastic programming, supplier selection

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Authors: Veronika Lesáková, Silvia Slezáková, František Štěpánek

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Additive manufacturing technologies producing drug dosage forms aimed at personalized medicine applications are promising strategies with several advantages over the conventional production methods. One of the emerging technologies is 3D printing which reduces manufacturing steps and thus allows a significant drop in expenses. A decrease in material consumption is also a highly impactful benefit as the tested drugs are frequently expensive substances. In addition, 3D printed dosage forms enable increased patient compliance and prevent misdosing as the dosage forms are carefully designed according to the patient’s needs. The incorporation of multiple drugs into a single dosage form further increases the degree of personalization. Our research focuses on the development of 3D printed tablets incorporating multiple drugs (candesartan, losartan) and thermoplastic polymers (e.g., KlucelTM HPC EF). The filaments, an essential feed material for 3D printing,wereproduced via hot-melt extrusion. Subsequently, the extruded filaments of various formulations were 3D printed into tablets using an FDM 3D printer. Then, we have assessed the influence of the internal structure of 3D printed tablets and formulation on dissolution behaviour by obtaining the dissolution profiles of drugs present in the 3D printed tablets. In conclusion, we have developed tablets containing multiple drugs providing modified release profiles. The 3D printing experiments demonstrate the high tunability of 3D printing as each tablet compartment is constructed with a different formulation. Overall, the results suggest that the 3D printing technology is a promising manufacturing approach to dual tablet preparation for personalized medicine.

Keywords: 3D printing, drug delivery, hot-melt extrusion, dissolution kinetics

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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: Sperisa Distantina, Fadilah, Mujtahid Kaavessina

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Crosslinked konjac glucomannan and kappa carrageenan film were prepared by chemical crosslinking using glutaraldehyde (GA) as the crosslinking agent. The effect crosslinking on the swelling degree was investigated. Konjac glucomanan and its mixture with kappa carragenan film was immersed in GA solution and then thermally cured. The obtained crosslinked film was washed and soaked in the ethanol to remove the unreacted GA. The obtained film was air dried at room temperature to a constant weight. The infrared spectra and the value of swelling degree of obtained crosslinked film showed that glucomannan and kappa carrageenan was able to be crosslinked using glutaraldehyde by film immersion and curing method without catalyst. The crosslinked films were found to be pH sensitive, indicating a potential to be used in drug delivery polymer system.

Keywords: crosslinking, glucomannan, carrageenan, swelling

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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: Stefan Gruden, Charlott Brunmark, Bo Holmqvist, Erwin D. Brenndorfer, Martin Johansson, Jian Liu, Ying Zhao, Niklas Axen, Moustapha Hassan

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Aim: The study was designed to evaluate the ability of the calcium sulfate-based NanoZolid® drug delivery technology to locally release the epidermal growth factor (EGF) protein while maintaining its biological activity. Methods: NanoZolid-formulated EGF protein labelled with a near-infrared dye (EGF-NIR) depots or EGF-NIR dissolved in PBS were injected subcutaneously into mice bearing EGF receptor (EGFR) positive human A549 lung cancer tumors inoculated subcutaneously. The release and biodistribution of the EGF-NIR were investigated in vivo longitudinally up to 96 hours post-administration, utilizing whole-body fluorescence imaging. In order to confirm the in vivo findings, histological analysis of tumor cryosections was performed to investigate EGF-NIR fluorescent signal and EGFR expression level by immunofluorescence labelling. Results: The in vivo fluorescence imaging showed a controlled release profile of the EGF-NIR loaded in the NanoZolid depots compared to free EGF-NIR. Histological analysis of the tumors further demonstrated a prevailing distribution of EGF-NIR in regions with high levels of EGFR expression. Conclusion: Calcium sulfate based depots can be used to formulate EGF while maintaining its biological activity, e.g., receptor binding capability. This may have good clinical potential for local delivery of biomolecules to enhance treatment efficacy and minimize systemic adverse effects.

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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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: Behcet Al, Şener Cindoruk, Suat Zengin, Mehmet Murat Oktay, Mehmet Mustafa Sunar, Hatice Eroglu, Cuma Yildirim

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Objective: In present study we aimed to investigate the chronic drug use due to chronic diseases in patients admitted to emergency department. Materials-Methods: 144 patients who applied to emergency department (ED) of medicine school of Gaziantep University between June 2013 and September 2013 with chronic diseases and use chronic drugs were included. Information about drugs used by patients were recorded. Results: Of patients, half were male, half were female, and the mean age was 58 years. The first three common diseases were diabetes mellitus, hypertension and coronary artery diseases. Of patients, %79.2 knew their illness. Fifty patients began to use drug within three months, 36 patient began to use within the last one year. While 42 patients brought all of their drugs with themselves, 17 patients brought along a portion of drugs. While three patients stopped their medication completely, 125 patients received medication on a regular basis. Fifty-two patient described the drugs with names, 13 patients described with their colors, 3 patients described by grammes, 45 patients described with the size of the tablet and 13 patients could not describe the drugs. Ninety-two patients explained which kind of drugs were used for each diseases, 17 patient explained partly, and 35 patients had no idea. Hundred patients received medication by themselves, 44 patients medications were giving by their relatives and med carers. Of medications, 140 were written by doctors directly, three medication were given by pharmacist; and one patient bought the drug by himself. For 11 patients the drugs were not harmonious to their diseases. Fifty-one patients admitted to the ED two times within last week, and 73 admitted two times within last month. Conclusion: The majority of patients with chronic diseases and use chronic drugs know their diseases and use the drugs in order, but do not have enough information about their medication.

Keywords: chronic disease, drug use, emergency department, medication

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Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

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The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

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The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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Authors: Krishna Dahiya, Esha Charaya

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Induction of labour is a common obstetrical intervention. Around 1 in every 4 patient undergo induction of labour for different indications Purpose: To study the efficacy of the combination of Foley bulb and vaginal misoprostol in comparison to vaginal misoprostol alone for cervical ripening and induction of labour. Methods: A prospective randomised study was conducted on 150 patients with term singleton pregnancy admitted for induction of labour. Seventy-five patients were induced with both Foley bulb, and vaginal misoprostol and another 75 were given vaginal misoprostol alone for induction of labour. Both groups were then compared with respect to change in Bishop score, induction to the active phase of labour interval, induction delivery interval, duration of labour, maternal complications and neonatal outcomes. Data was analysed using statistical software SPSS version 11.5. Tests with P,.05 were considered significant. Results: The two groups were comparable with respect to maternal age, parity, gestational age, indication for induction, and initial Bishop scores. Both groups had a significant change in Bishop score (2.99 ± 1.72 and 2.17 ± 1.48 respectively with statistically significant difference (p=0.001 S, 95% C.I. -0.1978 to 0.8378). Mean induction to delivery interval was significantly lower in the combination group (11.76 ± 5.89 hours) than misoprostol group (14.54 ± 7.32 hours). Difference was of 2.78 hours (p=0.018,S, 95% CI -5.1042 to -0.4558). Induction to delivery interval was significantly lower in nulliparous women of combination group (13.64 ± 5.75 hours) than misoprostol group (18.4±7.09 hours), and the difference was of 4.76 hours (p=0.002, S, 95% CI 1.0465 to 14.7335). There was no difference between the groups in the mode of delivery, infant weight, Apgar score and intrapartum complications. Conclusion: From the present study it was concluded that addition of Foley catheter to vaginal misoprostol have the synergistic effect and results in early cervical ripening and delivery. These results suggest that the combination may be used to achieve timely and safe delivery in the presence of an unfavorable cervix. A combination of the Foley bulb and vaginal misoprostol resulted in a shorter induction-to-delivery time when compared with vaginal misoprostol alone without increasing labor complications.

Keywords: Bishop score, Foley catheter, induction of labor, misoprostol

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Authors: Siphesihle Hlongwane

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Background: Globally, alcohol consumption, smoking, and the use of illicit drugs kill more than 11.8 million people each year. In sub-Saharan Africa, substance abuse is responsible for more than 6.4% of all deaths recorded and about 4.7% of all Disability Adjusted Life Years (DALYs), with numbers still expected to grow if no drastic measures are taken to curb and address drug use. In a setting where substance use is rife, understanding contextual factors that influence an individual’s perceived eligibility to seek rehabilitation is paramount. Using the candidacy framework, we unpack how situational factors influence an individual’s perceived eligibility for healthcare uptake in adolescents and youth with substance use disorder (SUD). Methods: The candidacy framework is concerned with how people consider their eligibility for accessing a health service. The study collected and analyzed primary qualitative data to answer the research question. Data were collected between January and July 2022 on participants aged between 18 and 35 for drug users and 18 to 60 for family members. Participants include 20 previous and current drug users and 20 family members that experience the effects of addiction. A pre-drafted semi-structured interview guide was administered to a conveniently sampled population supplemented with a referral sampling method. Data were thematically analyzed using the NVivo 12pro software to manage the data. Findings: Our findings show that people with substance use disorders are aware of their drug use habits and acknowledge their candidacy for health services. Candidacy for health services is also acknowledged by those around them, such as family members and peers, and as such, information on the navigation of health services for drug users is shared by those who have attended health services, those affected by drug use, and this includes health service research by family members to identify accessible health services. While participants reported willingness to quit drug use if assistance is provided, the permeability of health care services is hindered by both individual determinations to quit drug use from long-time use and the availability of health services for drug users, such as rehabilitation centers. Our findings also show that drug users are conscious and can articulate their ailments; however, the hunt for the next dose of drugs and long waiting cues for health service acquisition overshadows their claim to health services. Participants reported a mixture of treatments prescribed, with some more gruesome than others prescribed, thus serving as both a facilitator and barrier for health service uptake. Despite some unorthodox forms of treatments prescribed in health care, the majority of those who enter treatment complete the process of treatment, although some are met with setbacks and sometimes relapse after treatment has finished. Conclusion: Drug users are able to ascertain their candidacy for health services; however, individual and environmental characteristics relating to drug use hinder the use of health services. Drug use interventions need to entice health service uptake as a way to improve candidacy for health use.

Keywords: substance use disorder, rehabilitation, drug use, relapse, South Africa, candidacy framework

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Authors: Wanwimon Mekwimon

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Drug addiction is a serious problem in Thailand which has occurred continuously and repeatedly and enormously impacting health and economy of drug users. The indigenous wisdom and folk medicine is an attractive alternative choice, especially in detoxification and rehabilitation period. There are two objectives: First is to study about rehabilitation process and the curing for drug eaters and 2nd is to investigate the effectiveness of the curing and rehabilitation process by indigenous wisdom at Tamkrabok monastery, Pra-Puttabat district, Saraburi province. The main informants are 10 curers, 15 patients and 17 after-1-year rehabilitators. In the process, the semi-structured questionnaire is administered, the data are analyzed and proved by triangulation. The curing and rehabilitation process which use herbal remedies has a period of 15 days (5 days for detoxification and 10 days for recovery period) and the occupational training and self-consciousness awakening were delivered. The follow-up process includes twice-a-month recall for 6 months, follow-up letters and in depth interview with their families. The outcome of 1 year post-treatment was 94% (16 from 17). There are many reasons for not relapsing: the recovering patients have drawn on their inner strength, self-awareness and coping skill as well as their family and social support while rehabilitation process which includes difficulties in contacting with family members. They can void themselves from high risk situations to relapse. Recommendations: The follow-up system should be improved for continuous quality improvement, there should be the qualification standard for herbal remedies and the comparison among rehabilitation process of Tamkrabok and another methods are to be guideline for the further development.

Keywords: rehabilitation, drug addiction, Thai indigenous knowledge, herbal remedies

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Authors: F. Pires, V. Geraldo, O. N. Oliveira Jr., M. Raposo

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Catechins are powerful antioxidants which have attractive properties useful for tumor therapy. Considering their antioxidant activity, these molecules can act as a scavenger of the reactive oxygen species (ROS), alleviating the damage of cell membrane induced by oxidative stress. The complexity and dynamic nature of the cell membrane compromise the analysis of the biophysical interactions between drug and cell membrane and restricts the transport or uptake of the drug by intracellular targets. To avoid the cell membrane complexity, we used biomimetic systems as liposomes and Langmuir monolayers to study the interaction between catechin and membranes at the molecular level. Liposomes were formed after the dispersion of anionic 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)(sodium salt) (DPPG) phospholipids in an aqueous solution, which mimic the arrangement of lipids in natural cell membranes and allows the entrapment of catechins. Langmuir monolayers were formed after dropping amphiphilic molecules, DPPG phospholipids, dissolved in an organic solvent onto the water surface. In this work, we mixed epigallocatechin-3-gallate (EGCG) with DPPG liposomes and exposed them to ultra-violet radiation in order to evaluate the antioxidant potential of these molecules against oxidative stress induced by radiation. The presence of EGCG in the mixture decreased the rate of lipid peroxidation, proving that EGCG protects membranes through the quenching of the reactive oxygen species. Considering the high amount of hydroxyl groups (OH groups) on structure of EGCG, a possible mechanism to these molecules interact with membrane is through hydrogen bonding. We also investigated the effect of EGCG at various concentrations on DPPG Langmuir monolayers. The surface pressure isotherms and infrared reflection-absorption spectroscopy (PM-IRRAS) results corroborate with absorbance results preformed on liposome-model, showing that EGCG interacts with polar heads of the monolayers. This study elucidates the physiological action of EGCG which can be incorporated in lipid membrane. These results are also relevant for the improvement of the current protocols used to incorporate catechins in drug delivery systems.

Keywords: catechins, lipid membrane, anticancer agent, molecular interactions

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Authors: Tanvir Ahmed, Thanh N. Long, Phan T. Huong, Donald E. Stewart

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This paper presents views on condom use and the contexts of safe and unsafe sexual practices with different sexual partners and their relationships among Injecting Drug Users (IDUs) in Hai Phong, Vietnam. Fifteen IDUs participated and two local interviewers conducted qualitative semi-structured face-to-face interviews in September-October, 2012 in Vietnamese language. Data were analyzed thematically. Non-protective condom attitudes include negotiate or convince Female Sex Workers (FSW); not realizing risk, importance or necessity; partner doesn’t like, and having extra money/drug from clients. On the other hand, self-awareness, family-consciousness, suspicion of STI presence, fear of getting HIV, and client negotiation sometimes resulted in a safe-sex practice. A thematic diagram was developed to present the relationship (strong/weak) between condom attitude and sexual practice (safe/unsafe) by partner types. The experiences and views reflected in the qualitative information emphasize the heightened need for safe-sex education especially among young IDUs (male/female) highlighting sexual transmission risk.

Keywords: AIDS, HIV, injecting drug user, risk behaviors, Vietnam

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Authors: Jiyoung Kim, Chae Weon Chung

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Labor pain is one of the most common concerns of pregnant women, thus women are in need of possible options they could take to control the pain. So, this study aimed to explore maternal perception of epidural anesthesia and to compare the childbirth outcomes according to the use of epidural anesthesia. For this descriptive study, women who were over 36 weeks of pregnancy were recruited from an out-patient obstetric clinic in a public hospital in Seoul. Women were included in the study if agreed to participate, were pregnant singleton, without pregnancy complication, and expecting a natural birth. Data collection was done twice, the first one at the prenatal care visit and the second one at an in-patient ward on 2nd day postpartum. The instrument of the beliefs about epidural anesthesia, one item of asking intention to use epidural anesthesia, demographics, and obstetrical characteristics were incorporated into a questionnaire. One nurse researcher performed data collection with the structured questionnaire after the approval of the institutional review board. At the initial data collection 133 women were included, while 117 were retained at the second point after excluded 13 women due to the occurrence of complications. Analyses were done by chi-square, t-test, and ANOVA using the SPSS program. Women were aged 32.5 years old, 22.2% were over 35 years old. The average gestational age was 38.5 weeks, and 67.5% were nulliparous. Out of 38 multiparous women, 20 women (52.6%) had received epidural anesthesia in the previous delivery. At the initial interview, 62.6% (n=73) of women wanted to receive epidural anesthesia while 22.4% answered not decided and 15.4% did not want to take the procedure. However, there were changes in proportions between women’s intention to take it and actual procedures done, particularly, two-thirds of women (n=26) who had been undecided were found to receive epidural anesthesia during labor. There was a significant difference in the perception of epidural anesthesia measured before delivery between women who received and not received it (t=3.68, p < .001). Delivery outcomes were statistically different between the two groups in delivery mode (chi-square=8.64, p=.01), O₂ supply during labor (chi-square =5.01, p=.03), duration of 2nd stage of labor (t=3.70, p < .001), and arterial cord blood pH (t=2.64, p=.01). Interestingly, there was no difference in labor pain perceived between women with and without epidural anesthesia. Considering the preference and use of epidural anesthesia, health professionals need to assess coping ability of women undergoing delivery and to provide accurate information about pain control to support their decision making and eventually to enhance delivery outcomes for mothers and neonates.

Keywords: epidural anesthesia, delivery outcomes, labor pain, perception

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Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh

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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.

Keywords: corchorus olitorius, melanoma, drug development, strophanthidin

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Authors: Ane Escobar, Paula Angelomé, Mihaela Delcea, Marek Grzelczak, Sergio Enrique Moya

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The antibacterial capacity of bone-anchoring implants can be improved by the use of antibiotics that can be delivered to the media after the surgery. Mesoporous films have shown great potential in drug delivery for orthopedic applications, since pore size and thickness can be tuned to produce different surface area and free volume inside the material. This work shows the synthesis of mesoporous titania films (MTF) by sol-gel chemistry and evaporation-induced self-assembly (EISA) on top of glass substrates. Pores with a diameter of 12nm were observed by Transmission Electron Microscopy (TEM). A film thickness of 100 nm was measured by Scanning Electron Microscopy (SEM). Gentamicin was used to study the antibiotic delivery from the film by means of High-performance liquid chromatography (HPLC). The Staphilococcus aureus strand was used to evaluate the effectiveness of the penicillin loaded films toward inhibiting bacterial colonization. MC3T3-E1 pre-osteoblast cell proliferation experiments proved that MTFs have a good biocompatibility and are a suitable surface for MC3T3-E1 cell proliferation. Moreover, images taken by Confocal Fluorescence Microscopy using labeled vinculin, showed good adhesion of the MC3T3-E1 cells to the MTFs, as well as complex actin filaments arrangement. In order to improve cell proliferation Bone Morphogenetic Protein-2 (BMP-2) was adsorbed on top of the mesoporous film. The deposition of the protein was proved by measurements in the contact angle, showing an increment in the hydrophobicity while the protein concentration is higher. By measuring the dehydrogenase activity in MC3T3-E1 cells cultured in dually functionalized mesoporous titatina films with gentamicin and BMP-2 is possible to find an improvement in cell proliferation. For this purpose, the absorption of a yellow-color formazan dye, product of a water-soluble salt (WST-8) reduction by the dehydrogenases, is measured. In summary, this study proves that by means of the surface modification of MTFs with proteins and loading of gentamicin is possible to achieve an antibacterial effect and a cell growth improvement.

Keywords: antibacterial, biocompatibility, bone morphogenetic protein-2, cell proliferation, gentamicin, implants, mesoporous titania films, osteoblasts

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Authors: J. Klofac, P. Bazant, I. Kuritka

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This work is focused on the preparation of polymeric blend composed of polyamide (PA) and polyvinyl alcohol (PVA) with the intention to explore its basic characteristics important for potential use in medicine, especially for drug delivery systems. PA brings brilliant mechanical properties to the blend while PVA is inevitable due to its water solubility. Blend with different PA/PVA ratios were prepared and the release study of PVA into the water was carried out in a time interval 0-48 hours via the gravimetric method. The weight decrease is caused by the leaching of PVA domains what can be also followed by the optical and scanning electron microscopy. In addition, the thermal properties and the miscibility of blend components were evaluated by the differential scanning calorimeter. On the bases of performed experiments, it was found that the kinetics, continuity development and micro structure features of PA/PVA blends is strongly dependent on the blend composition and miscibility of its components.

Keywords: releas study, polyvinyl alcohol, polyamide morphology, polymeric blend

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Authors: Saravanan Govindaraju, Kyusik Yun

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The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

Procedia PDF Downloads 255