Search results for: implant assisted-magnetic drug targeting (IA-MDT)

Authors: M. Hirani, M. Devine, O. Obisesan, C. Bryant

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Introduction: The use of four or more implants to support a fixed prosthesis in the edentulous mandible is well documented, with high levels of clinical outcomes recorded. Despite this, the use of three implant-supported fixed prostheses offers the potential to deliver a more cost-effective method of oral rehabilitation in the lower arch, an important consideration given that edentulism is most prevalent in low-income subpopulations. The purpose of this study aimed to evaluate the implant and prosthetic survival rate, changes in marginal bone level, and patient satisfaction associated with a three-implant-supported fixed prosthesis for rehabilitation of the edentulous mandible over a follow-up period of at least one year. Methods: A comprehensive literature search was performed to evaluate studies that met the selection criteria. The information extracted included the study design and population, participant demographics, observation period, loading protocol, and the number of implants placed together with the required outcome measures. Mean values and standard deviations (SD) were calculated using SPSS® (IBM Corporation, New York, USA), and the level of statistical significance across all comparative studies described was set at P < 0.05. Results: The eligible studies included a total of 1968 implants that were placed in 652 patients. The subjects ranged in age from 33-89 years, with a mean of 63.2 years. The mean cumulative implant and prosthetic survival rates were 95.5% and 96.2%, respectively, over a mean follow-up period of 3.25 years. The mean marginal bone loss recorded was 1.04 mm, and high patient satisfaction rates were reported across the studies. Conclusion: Current evidence suggests that a three implant-supported fixed prosthesis for the edentulous mandible is a successful treatment strategy presenting high implant and prosthetic survival rates over the short-to-medium term. Further well-designed controlled clinical trials are required to evaluate longer-term outcomes, with supplemental data correlating implant dimensions and prosthetic design.

Keywords: implants, mandible, fixed, prosthesis

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Authors: Pimporn Thongmuang

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The import value of antimicrobial drugs reached approximately fifteen million Baht in 2010, considered as the highest import value of all modern drugs, and this value is rising every year. Antimicrobials are considered the hazardous drugs by the Ministry of Public Health. This research was conducted in order to investigate the past knowledge of drug use and Antimicrobial drug use behavior. A total of 757 students were selected as the samples out of a population of 1,800 students. This selected students had the experience of Antimicrobial drugs use a year ago. A questionnaire was utilized in this research. The findings put on the view that knowledge gained by the students about proper use of antimicrobial drugs was not brought into practice. This suggests that the education procedure regarding drug use needs adjustment. And therefore the findings of this research are expected to be utilized as guidelines for educating people about the proper use of antimicrobial drugs. At a broader perspective, correct drug use behavior of the public may potentially reduce drug cost of the Ministry of Public Health of Thailand.

Keywords: drug use knowledge, antimicrobial drugs, drug use behavior, drug

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Authors: Mazita Mohd Diah, Anton V. Dolzhenko, Tin Wui Wong

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Nanoparticles, being small with a large specific surface area, increase solubility, enhance bioavailability, improve controlled release and enable precision targeting of the entrapped compounds. In this study, chitosan as polymeric permeation enhancer was conjugated to a polar pro-drug, carboxymethyl-5-fluorouracil (CMFU) to increase the skin drug permeation. Chitosan-CMFU conjugate was synthesized using chemical conjugation process through succinate linker. It was then transformed into nanoparticles via spray drying method. The conjugation was elucidated using Fourier Transform Infrared and Proton Nuclear Magnetic Resonance techniques. The nanoparticle size, size distribution, zeta potential, drug content, skin permeation and retention profiles were characterized. The conjugation was denoted using 1H NMR by new peaks at signal δ = 4.184 ppm (singlet, 2H for CH2) and 7.676-7.688 ppm (doublet, 1H for C6) attributed to CMFU in chitosan-CMFU NMR spectrum. The nanoparticles had profiles of particle size: 93.97 ±35.11 nm, polydispersity index: 0.40 ± 0.14, zeta potential: +18.25 ±2.95 mV and drug content: 6.20 ± 1.98 % w/w. Almost 80 % w/w CMFU in the form of nanoparticles permeated through the skin in 24 hours and close to 50 % w/w permeation occurred in first 1-2 hours. Without conjugation to chitosan and nanoparticulation, less than 40 % w/w CMFU permeated through the skin in 24 hours. The skin drug retention likewise was higher with chitosan-CMFU nanoparticles (15.34 ± 5.82 % w/w) than CMFU (2.24 ± 0.57 % w/w). CMFU, through conjugation with chitosan permeation enhancer and processed in nanogeometry, had its skin permeation and retention degree promoted.

Keywords: carboxymethyl-5-fluorouracil, chitosan, conjugate, skin permeation, skin retention

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Authors: Monika Bansal

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Background: Placement of dental implant in narrow alveolar ridge is challenging to be treated. GBR procedure is currently most widely used to augment the deficient alveolar ridges and to treat the fenestration and dehiscence around dental implants. Thus, the objectives of the present study were to evaluate as well as compare the clinical performance of collagen membrane and titanium mesh for horizontal bone augmentation at dehisced implant sites. Methods and material: Total 12 single edentulous implant sites with buccal bone deficiency in 8 subjects were equally divided and treated simultaneously with either of the two membranes and DBBM(Bio-Oss) bone graft. Primary outcome measurements in terms of defect height and defect width were made using a calibrated plastic periodontal probe. Re-entry surgery was performed to remeasure the augmented site and to remove Ti-mesh at 6th month. Independent paired t-tests for the inter-group comparison and student-paired t-tests for the intra-group comparison were performed. The differences were considered to be significant at p ≤ 0.05. Results: Mean defect fill with respect to height and width was 3.50 ± 0.54 mm (87%) and 2.33 ± 0.51 mm (82%) for collagen membrane and 3.83 ± 0.75 mm (92%) and 2.50 ± 0.54 mm (88%) for Ti-mesh group respectively. Conclusions: Within the limitation of the study, it was concluded that mean defect height and width after 6 months were statistically significant within the group without significant difference between them, although defect resolution was better in Ti-mesh.

Keywords: collagen membrane, dehiscence, dental implant, horizontal bone, augmentation, ti-mesh

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Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

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Authors: Ayda Khosravanihaghighi, Pramod Koshy, Bill Walsh, Vedran Lovric, Charles Christopher Sorrell

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There is an increasing demand for orthopedic implants owing to the increasing numbers of the aging population. Titanium alloy (Ti6Al4V) is a common material used for orthopedic implants owing to its advantageous properties in terms of good corrosion resistance, minimal elastic modulus mismatch with bone, bio-inertness, and high mechanical strength. However, it is important to improve the bioactivity and osseointegration of the titanium alloy and this can be achieved by coating the implant surface with suitable ceramic materials. In the present work, pure and doped-ceria (CeO₂) coatings were deposited by spin coating on the titanium alloy surface in order to enhance the biological interactions between the surface of the implant and the surrounding tissue. In order to examine the bone-binding ability of an implant, simulated body fluid (SBF) tests were conducted in order to assess the capability of apatite layer formation on the surface and thus predict in vivo bone bioactivity. Characterization was done using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses to determine the extent of apatite formation. Preliminary tests showed that the CeO₂ coatings were biocompatible and that the extent of apatite formation and its characteristics can be enhanced by doping with suitable metal ions.

Keywords: apatite layer, biocompatibility, ceria, orthopaedic implant, SBF, spin coater, Ti-implant

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Shaker Alsharif, Xavier Banquy

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Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which chemists and chemical engineers are contributing to human health care. Such delivery systems provide numerous advantages compared to conventional dosage forms including improved efficacy, and improved patient compliance and convenience. Such systems often use synthetic polymers as carriers for the drugs. As a result, treatments that would not otherwise be possible are now in conventional use. The role of bilayered vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site avoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. Our project focuses on developing and building hydrogel with nanoinclusion of liposomes loaded with active compounds such as proteins and growth factors able to release them in a controlled fashion. In order to achieve that, we synthesize several liposomes of two different phospholipids concentrations encapsulating model drug. Then, formulating hydrogel with specific mechanical properties embedding the liposomes to manage the release of active compound.

Keywords: controlled release, hydrogel, liposomes, active compounds

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Authors: Madhu Gupta, G. P. Agrawa, Suresh P. Vyas

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Certain tumor cells overexpress a membrane-spanning molecule aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the NGR motif. NGR-modified Docetaxel (DTX)-loaded PEG-b-PLGA polymeric nanoparticles (cNGR-DNB-NPs) were developed and evaluated for their in vitro potential in HT-1080 cell line. The cNGR-DNB-NPs containing particles were about 148 nm in diameter with spherical shape and high encapsulation efficiency. Cellular uptake was confirmed both qualitatively and quantitatively by Confocal Laser Scanning Microscopy (CLSM) and flow cytometry. Both quantitatively and qualitatively results confirmed the NGR conjugated nanoparticles revealed the higher uptake of nanoparticles by CD13-overexpressed tumor cells. Free NGR inhibited the cellular uptake of cNGR-DNB-NPs, revealing the mechanism of receptor mediated endocytosis. In vitro cytotoxicity studies demonstrated that cNGR-DNB-NPs, formulation was more cytotoxic than unconjugated one, which were consistent well with the observation of cellular uptake. Hence, the selective delivery of cNGR-DNB-NPs formulation in CD13-overexpressing tumors represents a potential approach for the design of nanocarrier-based dual targeted delivery systems for targeting the tumor cells and vasculature.

Keywords: solid Tumor, docetaxel, targeting, NGR ligand

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Authors: Burcu Doymus, Fatma N. Kok, Sakip Onder

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Titanium and titanium-based materials are commonly used to replace or regenerate the injured or lost tissues because of accidents or illnesses. Hospital infections and strong bond formation at the implant-tissue interface are directly affecting the success of the implantation as weak bonding with the native tissue and hospital infections lead to revision surgery. The purpose of the presented study is to modify the surface of the titanium substrates with nano/microspheres for local drug delivery and to prevent hospital infections. Firstly, titanium surfaces were silanized with APTES (3-Triethoxysilylpropylamine) following the negatively charged oxide layer formation. Then characterization studies using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were done on the modified surfaces. Secondly, microspheres/nanospheres were prepared with chitosan that is a natural polymer and having valuable properties such as non-toxicity, high biocompatibility, low allergen city and biodegradability for biomedical applications. Antibiotic (ciprofloxacin) loaded micro/nanospheres have been fabricated using emulsion cross-linking method and have been immobilized onto the titanium surfaces with different immobilization techniques such as covalent bond and entrapment. Optimization studies on size and drug loading capacities of micro/nanospheres were conducted before the immobilization process. Light microscopy and SEM were used to visualize and measure the size of the produced micro/nanospheres. Loaded and released drug amounts were determined by using UV- spectrophotometer at 278 nm. Finally, SEM analysis and drug release studies on the micro/nanospheres coated Ti surfaces were done. As a conclusion, it was shown that micro/nanospheres were immobilized onto the surfaces successfully and drug release from these surfaces was in a controlled manner. Moreover, the density of the micro/nanospheres after the drug release studies was higher on the surfaces where the entrapment technique was used for immobilization. Acknowledgement: This work is financially supported by The Scientific and Technological Research Council Of Turkey (Project # 217M220)

Keywords: chitosan, controlled drug release, nanosphere, nosocomial infections, titanium

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Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Xing Wang, Lin Feng, Xuan Zou, Hongchen liu

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Immediate Implantation after tooth extraction is considered to be the ideal way to retain the alveolar bone, but some scholars believe the aesthetic effect in the Early Implantation case are more reliable. In this study, 89 patients were added to this retrospective study up to 5 years. Assessment indicators was including the survival of the implant (peri-implant infection, implant loosening, shedding, crowns and occlusal), aesthetics (color and fullness gums, papilla height, probing depth, X-ray alveolar crest height, the patient's own aesthetic satisfaction, doctors aesthetics score), repair defects around the implant (peri-implant bone changes in height and thickness, whether the use of autologous bone graft, whether to use absorption/repair manual nonabsorbable material), treatment time, cost and the use of antibiotics.The results demonstrated that there is no significant difference in long-term success rate of immediate implantation, early implantation and delayed implantation (p> 0.05). But the results indicated immediate implantation group could get get better aesthetic results after two years (p< 0.05), but may increase the risk of complications and failures (p< 0.05). High-risk indicators include gingival recession, labial bone wall damage, thin gingival biotypes, planting position and occlusal restoration bad and so on. No matter which type of implanting methods was selected, the extraction methods and bone defect amplification techniques are observed as a significant factors on aesthetic effect (p< 0.05).

Keywords: immediate implantation, long-term effects, aesthetics area, dental implants

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Authors: Serdal Akyüz, Halit Turan, Mehmet Öztürk

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The future security environment will have new battlefield and enemies. The boundaries of battlefield and the identity of enemies cannot be noticed easily. The politicians may not want to lose their soldiers in very risky operations. This approach will pave the way for smart machines like war robots and new drones. These machines will have the decision-making ability and act simultaneously. This ability can change the military targeting process. Military targeting process (MTP) benefits from a wide scope of lethal and non-lethal weapons to reach an intended end-state. This process is now managed by people but in the future smart machines can do it by themselves. At first sight, this development seems useful for humanity owing to decrease the casualties in war. Using robots -which can decide, detect, deliver and asses without human support- for homeland security and against terrorist has very crucial risks and threats. Besides, it can decrease the havoc but also increase the collateral damages. This paper examines the current use of smart war machines, military targeting process and presents a new approach to MTP from lethal autonomy concept's point of view.

Keywords: the autonomous weapon systems, the lethal autonomy, military targeting process (MTP)

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Cristian Crespo

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Conditional cash transfers (CCTs) have been targeted towards the poor. Thus, their targeting assessments check whether these schemes have been allocated to low-income households or individuals. However, CCTs have more than one goal and target group. An additional goal of CCTs is to increase school enrolment. Hence, students at risk of dropping out of school also are a target group. This paper analyses whether one of the most common targeting mechanisms of CCTs, a proxy means test (PMT), is suitable to identify the poor and future school dropouts. The PMT is compared with alternative approaches that use the outputs of a predictive model of school dropout. This model was built using machine learning algorithms and rich administrative datasets from Chile. The paper shows that using machine learning outputs in conjunction with the PMT increases targeting effectiveness by identifying more students who are either poor or future dropouts. This joint targeting approach increases effectiveness in different scenarios except when the social valuation of the two target groups largely differs. In these cases, the most likely optimal approach is to solely adopt the targeting mechanism designed to find the highly valued group.

Keywords: conditional cash transfers, machine learning, poverty, proxy means tests, school dropout prediction, targeting

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Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh, Fazel Zinat Motlagh

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Social support is an important benchmark of health for people in avoidance conditions. The main goal of this study was to determine the three kinds of social support (family, friend and other significant) to drug cessation among male addicts, in Kermanshah, the west of Iran. This cross-sectional study was conducted among 132 addicts, randomly selected to participate voluntarily in the study. Data were collected from conduct interviews based on standard questionnaire and analyzed by using SPSS-18 at 95% significance level. The majority of addicts were young (Mean: 30.4 years), and with little education. Opium (36.4%), Crack (21.2%), and Methamphetamine (12.9%) were the predominant drugs. Inabilities to reject the offer and having addict friends are the most often reasons for drug usage. Almost, 18.9% reported history of drug injection. 43.2% of the participants already did drug cessation at least once. Logistic regression showed the family support (OR = 1.110), age (OR = 1.106) and drug use initiation age (OR = 0.918) was predicting drug cessation. Our result showed; family support is a more important effect among types of social support in drug cessation. It seems that providing educational program to addict’s families for more support of patients at drug cessation can be beneficial.

Keywords: drug cessation, family support, drug use, initiation age

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Authors: Temesgen Geremew

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Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

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Authors: Masome Moeni, Roya Abedizadeh, Elham Aram, Hamid Sadeghi-Abandansari, Davood Sabour, Robert Menzel, Ali Hassanpour

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Significant number of studies and preclinical research in formulation of cancer nano-pharmaceutics have led to an improvement in cancer care. Nonetheless, the antineoplastic agents have ‘failed to live up to its promise’ since their clinical performance is moderately low. For almost ninety years, iron oxide nanoparticles (IONPS) have managed to keep its reputation in clinical application due to their low toxicity, versatility and multi-modal capabilities. Drug Administration approved utilization of IONPs for diagnosis of cancer as contrast media in magnetic resonance imaging, as heat mediator in magnetic hyperthermia and for the treatment of iron deficiency. Furthermore, IONPs have high drug-loading capacity, which makes them good candidates as therapeutic agent transporters. There are yet challenges to overcome for successful clinical application of IONPs, including stability of drug and poor delivery, which might lead to (i) drug resistance, (ii) shorter blood circulation time, and (iii) rapid elimination and adverse side effects from the system. In this study, highly stable and super paramagnetic IONPs were prepared for efficient and targeted drug delivery in cancer treatment. The synthesis procedure was briefly involved the production of IONPs via co-precipitation followed by coating with tetraethyl orthosilicate and 3-aminopropylethoxysilane and grafting with folic acid for stability targeted purposes and controlled drug release. Physiochemical and morphological properties of modified IONPs were characterised using different analytical techniques. The resultant IONPs exhibited clusters of 10 nm spherical shape crystals with less than 100 nm size suitable for drug delivery. The functionalized IONP showed mesoporous features, high stability, dispersibility and crystallinity. Subsequently, the functionalized IONPs were successfully loaded with oxaliplatin, a chemotherapeutic agent, for a controlled drug release in an actively targeting cancer cells. FT-IR observations confirmed presence of oxaliplatin functional groups, while ICP-MS results verified the drug loading was ~ 1.3%.

Keywords: cancer treatment, chemotherapeutic agent, drug delivery, iron oxide, multi-functional nanoparticle

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Authors: Adegoke Yinka Adebayo

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An understanding of the critical product attributes that impact on in vivo performance is key to the production of safe and effective medicines. Thus, a key driver for our research is the development of new basic science and technology underpinning the development of new pharmaceutical products. Research includes the structure and properties of drugs and excipients, biopharmaceutical characterisation, pharmaceutical processing and technology and formulation and analysis.

Keywords: drug discovery, drug development, drug delivery

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: S. Niamkaeo, O. Robert, O. Chaowalit

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In this investigation, we focus on discovering spatial relationship of drug smuggling along the northern border of Thailand. Thailand is no longer a drug production site, but Thailand is still one of the major drug trafficking hubs due to its topographic characteristics facilitating drug smuggling from neighboring countries. Our study areas cover three districts (Mae-jan, Mae-fahluang, and Mae-sai) in Chiangrai city and four districts (Chiangdao, Mae-eye, Chaiprakarn, and Wienghang) in Chiangmai city where drug smuggling of methamphetamine crystal and amphetamine occurs mostly. The data on drug smuggling incidents from 2011 to 2017 was collected from several national and local published news. Geo-spatial drug smuggling database was prepared. Decision tree algorithm was applied in order to discover the spatial relationship of factors related to drug smuggling, which was converted into rules using rule-based system. The factors including land use type, smuggling route, season and distance within 500 meters from check points were found that they were related to drug smuggling in terms of rules-based relationship. It was illustrated that drug smuggling was occurred mostly in forest area in winter. Drug smuggling exhibited was discovered mainly along topographic road where check points were not reachable. This spatial relationship of drug smuggling could support the Thai Office of Narcotics Control Board in surveillance drug smuggling.

Keywords: decision tree, drug smuggling, Geographic Information System, GIS knowledge discovery, rule-based system

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Authors: Serdal AKYUZ

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The smart power is the use of soft and hard power together in consideration of existing circumstances. Soft power can be defined as the capability of changing perception of any target mass by employing policies based on legality. The hard power, generally, uses military and economic instruments which are the concrete indicator of general power comprehension. More than providing a balance between soft and hard power, smart power creates a proactive combination by assessing existing resources. Military targeting process (MTP), as stated in smart power methodology, benefits from a wide scope of lethal and non-lethal weapons to reach intended end state. The Smart powers components can be used in military targeting process similar to using of lethal or non-lethal weapons. This paper investigates the current use of Smart power concept, MTP and presents a new approach to MTP from smart power concept point of view.

Keywords: future security environment, hard power, military targeting process, soft power, smart power

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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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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Authors: Susmita Roy, Madhavan Nallani

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In recent years' polymersomes, self-assembled polymeric vesicles emerge from block copolymers, have been widely investigated due to their enhance stability and unique advantageous properties compared to their phospholipid counterpart, liposomes, dendrimers, and micelles. It provides a distinctive platform for advanced therapeutics and the creation of complex (bio) catalytically active systems for research in Nanomedicine and synthetic biology. Inspired by nature, where compartmentalization of biological components is all ubiquitous, we are interested in developing a platform technology of self-assembled multifunctional compartments with applications in areas from targeted drug/gene delivery, biosensing, pharmaceutical to cosmetics. Polymersome surfaces can be a proper choice of derivatization with a controlled amount of functional groups. To achieve site-specific targeting of polymersomes, biological recognition motives can be attached to the polymersomes surface by standard bioconjugation techniques, (like esterification, amidation, thiol-maleimide coupling, click-chemistry routes or other coupling methods). Herein, we are developing easy going, one-step bioconjugation strategies for site-specific surface functionalized biodegradable polymeric and/or polymer-lipid hybrid vesicles for targeted drug delivery. Biodegradable polymer, polycaprolactone-b-polyethylene glycol (PCL-PEG), polylactic acid-b-polyethylene glycol (PLA-PEG) and phospholipid, 1-palmitoyl-2- oleoyl-sn-glycero-3-phosphocholine (POPC) has been widely used for numerous vesicle formulations. Some of these drug-loaded formulations are being tested on mice for controlled release. These surface functionalized polymersomes are also appropriate for membrane protein reconstitution/insertion, antibodies conjugation and various bioconjugation with diverse targeted molecules for controlled drug delivery.

Keywords: drug delivery, membrane protein, polymersome, surface modification

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Authors: S. Reshma Reghu, Shiburaj Sugathan, T. G. Nandu, K. B. Ramesh Kumar, Mathew Dan

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Bacterial diseases are considered to be one of the most prevalent health hazards in the developing world and many bacteria are becoming resistant to existing antibiotics making the treatment ineffective. Thus, it is necessary to find novel targets and develop new antibacterial drugs with a novel mechanism of action. The process of bacterial cell division is a novel and attractive target for new antibacterial drug discovery. FtsZ, a homolog of eukaryotic tubulin, is the major protein of the bacterial cell division machinery and is considered as an important antibacterial drug target. Zingiberaceae, the Ginger family consists of aromatic herbs with creeping rhizomes. Many of these plants have antimicrobial properties.This study aimed to determine the anti-bacterial activity of selected Zingiberaceous plants by targeting bacterial cell division protein, FtsZ. Essential oils and methanol extracts of Amomum ghaticum, Alpinia galanga, Kaempferia galanga, K. rotunda, and Zingiber officinale were tested to find its antibacterial efficiency using disc diffusion method against authentic bacterial strains obtained from MTCC (India). Essential oil isolated from A.galanga and Z.officinale were further assayed for FtsZ inhibition assay following non-radioactive malachite green-phosphomolybdate assay using E. coli FtsZ protein obtained from Cytoskelton Inc., USA. Z.officinale essential oil possess FtsZ inhibitory property. A molecular docking study was conducted with the known bioactive compounds of Z. officinale as ligands with the E. coli FtsZ protein homology model. Some of the major constituents of this plant like catechin, epicatechin, and gingerol possess agreeable docking scores. The results of this study revealed that several chemical constituents in Ginger plants can be utilised as potential source of antibacterial activity and it can warrant further investigation through drug discovery studies.

Keywords: antibacterial, FtsZ, zingiberaceae, docking

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Authors: Yann Jean Tan, Hui Meng Er, Choy Sin Lee, Shew Fung Wong, Wen Huei Lim

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Griseofulvin is a long standing fungistatic agent against dermatophytosis. Nevertheless, it has several drawbacks such as poor and highly variable bio availability, long duration of treatment, systemic side effects and drug interactions. Targeted treatment for the superficial skin infection, dermatophytosis via topical route could be beneficial. Nevertheless, griseofulvin is only available in the form of oral preparation. Hence, it generates interest in developing a topical formulation for griseofulvin, by using lipid nano particle as the vehicle. Lipid nanoparticle is a submicron colloidal carrier with a core that is solid in nature (lipid). It has combined advantages of various traditional carriers and is a promising vehicle for topical delivery. The griseofulvin loaded lipid nano particles produced using high pressure homogenization method were characterized and investigated for its skin targeting effect in vitro. It has a mean particle size of 179.8±4.9 nm with polydispersity index of 0.306±0.011. Besides, it showed higher skin permeation and better skin targeting effect compared to the griseofulvin suspension.

Keywords: lipid nanoparticles, griseofulvin, topical, dermatophytosis

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Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh

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Background: Substance addiction is one of the major worldwide problems that destroys economy, familial relationships, and the abuser’s career and has several side effects; in the meantime drug injection due to the possibility of shared use of syringes among drug users could have multiple complications to be followed. The purpose of this study was to determine the prevalence of drug injection among male prisoners in Kermanshah city, the west of Iran. Methods: In this cross-sectional study 615 male prisoners were randomly selected to participate voluntarily in the study. Participants filled out a writing self-report questionnaire. Data were analyzed by the SPSS software (ver. 21.0) at 95% significant level. Results: The mean age of respondents was 31.13 years [SD: 7.76]. Mean initiation age for drug use was 14.36 years (range, 9-34 years). Almost, 39.4 % reported a history of drug use before prison. Opium (33.2%) and crystal (27.1%) was the most used drug among prisoners. Furthermore, 9.3 % had a history of injection addiction. There was a significant correlation between age, crime type, marital status, economic status, unprotected sex and drug injection (P < 0.05). Conclusion: The low age of drug abuse and the prevalence of drug injection among offenders can be as a warning for responsible; in this regard, implementation of prevention programs to risky behavior and harm reduction among high-risk groups can follow useful results.

Keywords: substance abuse, drug injection, prison, Iran

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Authors: Raj Kumar, Prem Felix Siril

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The poor aqueous solubility of many pharmaceutical drugs and potential drug candidates is a big challenge in drug development. Nanoformulation of such candidates is one of the major solutions for the delivery of such drugs. We initially developed the evaporation assisted solvent-antisolvent interaction (EASAI) method. EASAI method is use full to prepared nanoparticles of poor water soluble drugs with spherical morphology and particles size below 100 nm. However, to further improve the effect formulation to reduce number of dose and side effect it is important to control the delivery of drugs. However, many drug delivery systems are available. Among the many nano-drug carrier systems, solid lipid nanoparticles (SLNs) have many advantages over the others such as high biocompatibility, stability, non-toxicity and ability to achieve controlled release of drugs and drug targeting. SLNs can be administered through all existing routes due to high biocompatibility of lipids. SLNs are usually composed of lipid, surfactant and drug were encapsulated in lipid matrix. A number of non-steroidal anti-inflammatory drugs (NSAIDs) have poor bioavailability resulting from their poor aqueous solubility. In the present work, SLNs loaded with NSAIDs such as Nabumetone (NBT), Ketoprofen (KP) and Ibuprofen (IBP) were successfully prepared using different lipids and surfactants. We studied and optimized experimental parameters using a number of lipids, surfactants and NSAIDs. The effect of different experimental parameters such as lipid to surfactant ratio, volume of water, temperature, drug concentration and sonication time on the particles size of SLNs during the preparation using hot-melt sonication was studied. It was found that particles size was directly proportional to drug concentration and inversely proportional to surfactant concentration, volume of water added and temperature of water. SLNs prepared at optimized condition were characterized thoroughly by using different techniques such as dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and differential scanning calorimetry and Fourier transform infrared spectroscopy (FTIR). We successfully prepared the SLN of below 220 nm using different lipids and surfactants combination. The drugs KP, NBT and IBP showed 74%, 69% and 53% percentage of entrapment efficiency with drug loading of 2%, 7% and 6% respectively in SLNs of Campul GMS 50K and Gelucire 50/13. In-vitro drug release profile of drug loaded SLNs is shown that nearly 100% of drug was release in 6 h.

Keywords: nanoparticles, delivery, solid lipid nanoparticles, hot-melt sonication, poor water soluble drugs, solubility, bioavailability

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