Search results for: drug release model

Authors: Mahsa Fathollahzadeh

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The various nanoparticles employed in drug delivery applications include micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, and nanotubes. Micelles, composed of amphiphilic block copolymers, can encapsulate hydrophobic molecules, allowing for targeted delivery. Liposomes, vesicular structures made up of phospholipids, can encapsulate both hydrophobic and hydrophilic molecules, providing a flexible platform for delivering therapeutic agents. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are designed to improve the stability and bioavailability of lipophilic drugs. Polymeric nanoparticles, such as poly(lactic-co-glycolic acid) (PLGA), are biodegradable and can be engineered to release drugs in a controlled manner. Functionalized nanoparticles, coated with targeting ligands or antibodies, can specifically target diseased cells or tissues. Nanocrystals, engineered to have specific surface properties, can enhance the solubility and bioavailability of poorly soluble drugs. Cyclodextrins, doughnut-shaped molecules with hydrophobic cavities, can be complex with hydrophobic molecules, allowing for improved solubility and bioavailability. Dendrimers, branched polymers with a central core, can be designed to deliver multiple therapeutic agents simultaneously. Nanotubes and metallic nanoparticles, such as gold nanoparticles, offer real-time tracking capabilities and can be used to detect biomolecular interactions. The use of these nanoparticles has revolutionized the field of drug delivery, enabling targeted and controlled release of therapeutic agents, reduced toxicity, and improved patient outcomes.

Keywords: nanotechnology, nanopharmaceuticals, drug-delivery, proteins, ligands, nanoparticles, chemistry

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Authors: Atinderpal Kaur, Shweta Dang

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

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

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Authors: Mohammad Hamed Asosheh

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The development of nanobiomaterials has opened new avenues in the field of biomedical engineering, offering unparalleled possibilities for advanced therapeutic applications. This study explores the synthesis and characterization of a distinct class of nanobiomaterials designed to enhance drug delivery systems and support tissue engineering. By integrating biodegradable polymers with bioactive nanoparticles, we have engineered a multifunctional platform that ensures controlled drug release, targeted delivery, and improved biocompatibility. Our findings demonstrate that these nanobiomaterials not only exhibit excellent mechanical properties but also promote cell proliferation and differentiation, making them ideal candidates for regenerative medicine. Furthermore, in vitro and in vivo assessments reveal that the engineered materials significantly reduce cytotoxicity while enhancing the therapeutic efficacy of encapsulated drugs. This research presents a promising approach to addressing current challenges in drug delivery and tissue regeneration, with the potential to revolutionize the treatment of chronic diseases and injury repair. Future work will focus on optimizing the material composition for specific clinical applications and conducting large-scale studies to evaluate long-term safety and effectiveness.

Keywords: nanobiomaterials, drug delivery systems, therapeutic efficacy, bioactive nanoparticles

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Authors: Rishav Shrestha, Yong Zhang

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The Anti-Stoke upconversion process has been used extensively for bioimaging and is recently being used for photoactivated therapy in cancer utilizing upconversion nanoparticles (UCNs). The UCNs have an excitation band at 980nm; 980nm laser excitation used to produce UV/Visible emissions also produce a heating effect. Light-to-heat conversion has been observed in nanoparticles(NPs) doped with neodymium(Nd) or ytterbium(Yb)/erbium(Er) ions. Despite laser-induced heating in Rare-earth doped NPs being proven to be a relatively efficient process, only few attempts to use them as photothermal agents in biosystems have been made up to now. Gold nanoparticles and carbon nanotubes are the most researched and developed for photothermal applications. Both have large heating efficiency and outstanding biocompatibility. However, they show weak fluorescence which makes them harder to track in vivo. In that regard, UCNs are attractive due to their excellent optical features in addition to their light-to-heat conversion and excitation by NIR, for imaging and spatiotemporally releasing drugs. In this work, we have utilized a simple method to coat Nd doped UCNs with thermoresponsive polymer PNIPAM on which 4-Hydroxytamoxifen (4-OH-T) is loaded. Such UCNs demonstrate a high loading efficiency and low leakage of 4-OH-T. Encouragingly, the release of 4-OH-T can be modulated by varying the power and duration of the NIR. Such UCNs were then used to demonstrate imaging and controlled photothermal release of 4-OH-T in MCF-7 breast cancer cells.

Keywords: cancer therapy, controlled release, photothermal release, upconversion nanoparticles

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Authors: Mary Konadu

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The rectal route for drug administration is becoming attractive to drug formulators because it can avoid hepatic first-pass effects, decrease gastrointestinal side effects and avoid undesirable effects of meals on drug absorption. Suppositories have been recognized as an alternative to the oral route in situations such as when the patient is comatose, unable to swallow, or when the drug produces nausea or vomiting. Effective drug delivery with appropriate pharmaceutical excipient is key in the production of clinically useful preparations. The high cost of available excipients coupled with other disadvantages have led to the exploration of potential excipients from natural sources. Allanblackia floribunda butter, a naturally occurring lipid, is used for medicinal, culinary, and cosmetic purposes. Different extraction methods (solvent (hexane) extraction, traditional/hot water extraction, and cold/screw press extraction) were employed to extract the oil. The different extracts of A. floribunda oil were analyzed for their physicochemical properties and mineral content. The oil was used as a base to formulate Paracetamol and Diclofenac suppositories. Quality control test were carried out on the formulated suppositories. The %age oil yield for hexane extract, hot water extract, and cold press extract were 50.40 ±0.00, 37.36±0.00, and 20.48±0.00, respectively. The acid value, saponification value, iodine value and free fatty acid were 1.159 ± 0.065, 208.51 ± 8.450, 49.877 ± 0.690 and 0.583 ± 0.032 respectively for hexane extract; 3.480 ± 0.055, 204.672±2.863, 49.04 ± 0.76 and 1.747 ± 0.028 respectively for hot water/traditional extract; 4.43 ± 0.055, 192.05±1.56, 49.96 ± 0.29 and 2.23 ± 0.03 respectively for cold press extract. Calcium, sodium, magnesium, potassium, and iron were minerals found to be present in the A. floribunda butter extracts. The uniformity of weight, hardness, disintegration time, and uniformity of content were found to be within the acceptable range. The melting point ranges for all the suppositories were found to be satisfactory. The cumulative drug release (%) of the suppositories at 45 minutes was 90.19±0.00 (Hot water extract), 93.75±0.00 (Cold Pres Extract), and 98.16±0.00 (Hexane Extract) for Paracetamol suppositories. Diclofenac sodium suppositories had a cumulative %age release of 81.60±0.00 (Hot water Extract), 95.33±0.00 (Cold Press Extract), and 99.20±0.00 (Hexane Extract). The physicochemical parameters obtained from this study shows that Allanblackia floribunda seed oil is edible and can be used as a suppository base. The suppository formulation was successful, and the quality control tests conformed to Pharmacopoeia standard.

Keywords: allanblackia foribunda, paracetamol, diclofenac, suppositories

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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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: Jiwan P. Lavande, A. V. Chandewar

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In the present study, orodispersible tablets of diphenhydramine hydrochloride were prepared using croscarmellose sodium, crospovidone and camphor, menthol (as subliming agents) in different ratios and ODTs prepared with superdisintegrants were compared with ODTs prepared with camphor and menthol (subliming agents) for the following evaluation of in vitro disintegration time, dispersion time, wetting time, hardness and water absorption ratio. Results revealed that the tablets of all formulations have acceptable physical parameters. The drug and excipients compatibility study was evaluated using FTIR technique and has not detected any incompatibility. The in vitro release of drug from DC6 formulation was quick when compared to other formulations. Stability study was carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets had not shown any significant difference. Microscopic study of different formulations of sublimed tablets showed formation of pores for the tablets prepared by sublimation method. Thus, conclusion can be made that the stable orodispersible tablets of diphenhydramine hydrochloride can be developed for the rapid release of diphenhydramine hydrochloride.

Keywords: orodispersible tablet, subliming agent, super disintegrants, diphenhydramine hydrochloride

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Authors: G. Wagner, R. Herrmann

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Cytotoxic platinum compounds play a major role in the chemotherapy of a large number of human cancers. However, due to the severe side effects for the patient and other problems associated with their use, there is a need for the development of more efficient drugs and new methods for their selective delivery to the tumours. One way to achieve the latter could be in the use of nanoparticular substrates that can adsorb or chemically bind the drug. In the cell, the drug is supposed to be slowly released, either by physical desorption or by dissolution of the particle framework. Ideally, the cytotoxic properties of the platinum drug unfold only then, in the cancer cell and over a longer period of time due to the gradual release. In this paper, we report on our first steps in this direction. The binding properties of a series of cytotoxic Pt(II) oxadiazoline compounds to mesoporous silica particles has been studied by NMR and UV/vis spectroscopy. High loadings were achieved when the Pt(II) compound was relatively polar, and has been dissolved in a relatively nonpolar solvent before the silica was added. Typically, 6-10 hours were required for complete equilibration, suggesting the adsorption did not only occur to the outer surface but also to the interior of the pores. The untreated and Pt(II) loaded particles were characterised by C, H, N combustion analysis, BET/BJH nitrogen sorption, electron microscopy (REM and TEM) and EDX. With the latter methods we were able to demonstrate the homogenous distribution of the Pt(II) compound on and in the silica particles, and no Pt(II) bulk precipitate had formed. The in vitro cytotoxicity in a human cancer cell line (HeLa) has been determined for one of the new platinum compounds adsorbed to mesoporous silica particles of different size, and compared with the corresponding compound in solution. The IC50 data are similar in all cases, suggesting that the release of the Pt(II) compound was relatively fast and possibly occurred before the particles reached the cells. Overall, the platinum drug is chemically stable on silica and retained its activity upon prolonged storage.

Keywords: cytotoxicity, mesoporous silica, nanoparticles, platinum compounds

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Raquel Galante, Marina Braga, Daniela Ghisleni, Terezinha J. A. Pinto, Rogério Colaço, Ana Paula Serro

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The sensitive nature of soft biomaterials, such as hydrogels, renders their sterilization a particularly challenging task for the biomedical industry. Widely used contact lenses are now studied as promising platforms for topical corneal drug delivery. However, to the best of the authors knowledge, the influence of sterilization methods on these systems has yet to be evaluated. The main goal of this study was to understand how different pairs drug-hydrogel would interact under an ozone-based sterilization method in comparison with two conventional processes (steam heat and gamma irradiation). For that, Si-Hy containing hydroxylethyl methacrylate (HEMA) and [tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS) was produced and soaked in different drug solutions, commonly used for the treatment of ocular diseases (levofloxacin, chlorhexidine, diclofenac and timolol maleate). The drug release profiles and main material properties were evaluated before and after the sterilization. Namely, swelling capacity was determined by water uptake studies, transparency was accessed by UV-Vis spectroscopy, surface topography/morphology by scanning electron microscopy (SEM) and mechanical properties by performing tensile tests. The drug released was quantified by high performance liquid chromatography (HPLC). The effectiveness of the sterilization procedures was assured by performing sterility tests. Ozone gas method led to a significant reduction of drug released and to the formation of degradation products specially for diclofenac and levofloxacin. Gamma irradiation led to darkening of the loaded Si-Hys and to the complete degradation of levofloxacin. Steam heat led to smoother surfaces and to a decrease of the amount of drug released, however, with no formation of degradation products. This difference in the total drug released could be the related to drug/polymer interactions promoted by the sterilization conditions in presence of the drug. Our findings offer important insights that, in turn, could be a useful contribution to the safe development of actual products.

Keywords: drug delivery, silicone hydrogels, sterilization, gamma irradiation, steam heat, ozone gas

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Authors: A. M. H. Shokry, N. S. M. El-Tayeb

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The environmental impacts caused by fertilizers call for the adaptation of more sustainable technologies in order to increase agricultural production and reduce pollution due to high nutrient emissions. One particular technique has been to coat urea fertilizer granules with less-soluble chemicals that permit the gradual release of nutrients in a slow and controlled manner. The aim of this research is to develop a biodegradable slow-release fertilizer (SRF) with materials that come from sustainable sources; starch and polyvinyl alcohol (PVA). The slow-release behavior and water retention capacity of the coated granules were determined. In addition, the aqueous release and absorbency rates were also tested. Results confirmed that the release rate from coated granules was slower than through plain membranes; and that the water absorption capacity of the coated urea decreased as PVA content increased. The SRF was also tested and gave positive results that confirmed the integrity of the product.

Keywords: biodegradability, nitrogen-use efficiency, poly-vinyl alcohol, slow-release fertilizer, sustainability

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Authors: Melkamu Tadesse Getachew

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Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

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Authors: Surya R. Niraula, Devendra B Chhetry, Girish K. Singh, S. Nagesh, Frederick A. Connell

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Background: Although random sampling is generally considered to be the gold standard for population-based research, the majority of drug abuse research is based on non-random sampling despite the well-known limitations of this kind of sampling. Method: We compared the statistical properties of two surveys of drug abuse in the same community: one using snowball sampling of drug users who then identified “friend controls” and the other using a random sample of non-drug users (controls) who then identified “friend cases.” Models to predict drug abuse based on risk factors were developed for each data set using conditional logistic regression. We compared the precision of each model using bootstrapping method and the predictive properties of each model using receiver operating characteristics (ROC) curves. Results: Analysis of 100 random bootstrap samples drawn from the snowball-sample data set showed a wide variation in the standard errors of the beta coefficients of the predictive model, none of which achieved statistical significance. One the other hand, bootstrap analysis of the random-sample data set showed less variation, and did not change the significance of the predictors at the 5% level when compared to the non-bootstrap analysis. Comparison of the area under the ROC curves using the model derived from the random-sample data set was similar when fitted to either data set (0.93, for random-sample data vs. 0.91 for snowball-sample data, p=0.35); however, when the model derived from the snowball-sample data set was fitted to each of the data sets, the areas under the curve were significantly different (0.98 vs. 0.83, p < .001). Conclusion: The proposed method of random sampling of controls appears to be superior from a statistical perspective to snowball sampling and may represent a viable alternative to snowball sampling.

Keywords: drug abuse, matched case-control study, non-probability sampling, probability sampling

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Authors: Florin G. Borcan, Ramona C. Albulescu, Adela Chirita-Emandi

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pH-responsive drug delivery systems are gaining more importance because these systems deliver the drug at a specific time in regards to pathophysiological necessity, resulting in improved patient therapeutic efficacy and compliance. Polyurethane materials are well-known for industrial applications (elastomers and foams used in different insulations and automotive), but they are versatile biocompatible materials with many applications in medicine, as artificial skin for the premature neonate, membrane in the hybrid artificial pancreas, prosthetic heart valves, etc. This study aimed to obtain the physico-chemical characterization of a drug delivery system based on polyurethane microparticles. The synthesis is based on a polyaddition reaction between an aqueous phase (mixture of polyethylene-glycol M=200, 1,4-butanediol and Tween® 20) and an organic phase (lysin-diisocyanate in acetone) combined with simultaneous emulsification. Different active agents (omeprazole, amoxicillin, metoclopramide) were used to verify the release profile of the macromolecular particles in different pH mediums. Zetasizer measurements were performed using an instrument based on two modules: a Vasco size analyzer and a Wallis Zeta potential analyzer (Cordouan Technol., France) in samples that were kept in various solutions with different pH and the maximum absorbance in UV-Vis spectra were collected on a UVi Line 9,400 Spectrophotometer (SI Analytics, Germany). The results of this investigation have revealed that these particles are proper for a prolonged release in gastric medium where they can assure an almost constant concentration of the active agents for 1-2 weeks, while they can be disassembled faster in a medium with neutral pHs, such as the intestinal fluid.

Keywords: lysin-diisocyanate, nanostructures, polyurethane, Zetasizer

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Authors: Gabriel Sanjo Aruwajoye, E. B. Gueguim Kana

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Agricultural residues present a low-cost feedstock for bioenergy production around the world. Cassava peels waste are rich in organic molecules that can be readily converted to value added products such as biomaterials and biofuels. However, due to the presence of high proportion of structural carbohydrates and lignin, the hydrolysis of this feedstock is imperative to achieve maximum substrate utilization and energy yield. This study model and optimises the release of Fermentable Sugar (FS) from cassava peels waste using the Response Surface Methodology. The investigated pretreatment input parameters consisted of soaking temperature (oC), soaking time (hours), autoclave duration (minutes), acid concentration (% v/v), substrate solid loading (% w/v) within the range of 30 to 70, 0 to 24, 5 to 20, 0 to 5 and 2 to 10 respectively. The Box-Behnken design was used to generate 46 experimental runs which were investigated for FS release. The obtained data were used to fit a quadratic model. A coefficient of determination of 0.87 and F value of 8.73 was obtained indicating the good fitness of the model. The predicted optimum pretreatment conditions were 69.62 oC soaking temperature, 2.57 hours soaking duration, 5 minutes autoclave duration, 3.68 % v/v HCl and 9.65 % w/v solid loading corresponding to FS yield of 91.83g/l (0.92 g/g cassava peels) thus 58% improvement on the non-optimised pretreatment. Our findings demonstrate an efficient pretreatment model for fermentable sugar release from cassava peels waste for various bioprocesses.

Keywords: feedstock pretreatment, cassava peels, fermentable sugar, response surface methodology

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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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: Jung Hyun Kim, Gyo Woo Lee

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In this study, heat release performances of the three extruded-type heat sinks can be used in the inverter for solar power generation were evaluated. Numbers of fins in the heat sinks (namely E-38, E-47 and E-76) were 38, 47 and 76, respectively. Heat transfer areas of them were 1.8, 1.9 and 2.8 m2. The heat release performances of E-38, E-47, and E-76 heat sinks were measured as 79.6, 81.6, and 83.2%, respectively. The results of heat release performance show that the larger amount of heat transfer area the higher heat release rate. While on the other, in this experiment, variations of the mass flow rates caused by different cross-sectional areas of the three heat sinks may not be the major parameter of the heat release. Despite the 47.4% increment of heat transfer area of E-76 heat sink than that of E-47 one, its heat release rate was higher by only 2.0%; this suggests that its heat transfer area need to be optimized.

Keywords: solar Inverter, heat sink, forced convection, heat transfer, performance evaluation

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Authors: A. Maruf Aytekin

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We present our approach on using continuous delivery pattern for release management. One of the key practices of agile and lean teams is the continuous delivery of new features to stakeholders. The main benefits of this approach lie in the ability to release new applications rapidly which has real strategic impact on the competitive advantage of an organization. Organizations that successfully implement Continuous Delivery have the ability to evolve rapidly to support innovation, provide stable and reliable software in more efficient ways, decrease the amount of resources need for maintenance, and lower the software delivery time and costs. One of the objectives of this paper is to elaborate a case study where IT division of Central Securities Depository Institution (MKK) of Turkey apply Continuous Delivery pattern to improve release management process.

Keywords: automation, continuous delivery, deployment, release management

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Authors: Vera Sovkova, Andrea Mickova, Matej Buzgo, Karolina Vocetkova, Eva Filova, Evzen Amler

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PCL (poly-ε-caprolactone) nanofibrous scaffolds with adhered liposomes were prepared and tested as a possible drug delivery system for various synthetic growth factors. TGFβ, bFGF, and IGF-I have been shown to increase hMSC (human mesenchymal stem cells) proliferation and to induce hMSC differentiation. Functionalized PCL nanofibers were prepared with synthetic growth factors encapsulated in liposomes adhered to them in three different concentrations. Other samples contained PCL nanofibers with adhered, free synthetic growth factors. The synthetic growth factors free medium served as a control. The interaction of liposomes with the PCL nanofibers was visualized by SEM, and the release kinetics were determined by ELISA testing. The potential of liposomes, immobilized on the biodegradable scaffolds, as a delivery system for synthetic growth factors, and as a suitable system for MSCs adhesion, proliferation and differentiation in vitro was evaluated by MTS assay, dsDNA amount determination, confocal microscopy, flow cytometry and real-time PCR. The results showed that the growth factors adhered to the PCL nanofibers stimulated cell proliferation mainly up to day 11 and that subsequently their effect was lower. By contrast, the release of the lowest concentration of growth factors from liposomes resulted in gradual proliferation of MSCs throughout the experiment. Moreover, liposomes, as well as free growth factors, stimulated type II collagen production, which was confirmed by immunohistochemical staining using monoclonal antibody against type II collagen. The results of this study indicate that growth factors enriched liposomes adhered to surface of PCL nanofibers could be useful as a drug delivery instrument for application in short timescales, be combined with nanofiber scaffolds to promote local and persistent delivery while mimicking the local microenvironment. This work was supported by project LO1508 from the Ministry of Education, Youth and Sports of the Czech Republic

Keywords: drug delivery, growth factors, hMSC, liposomes, nanofibres

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Authors: Yuan Yang, Mickey Lam

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Oral dissolvable films have been considered as a unique alternative approach to conventional oral dosage forms. The films could be administrated via the gastrointestinal tract as conventional dosages or through sublingual/buccal mucosa membranes, which could enhance drug bioavailability by avoiding the first-pass effect and improving permeability due to high blood flow and lymphatic circulation. This work has described a state-of-art technic using nano-emulsion/nano-suspension as a precursor for the film to enhance the bioavailability of BCS class II drugs. The drug molecules are consequentially processed through the emulsification, gelation, and film-casting processes. The gelation process is critical to stabilizing the nano-emulsion for the film-casting as well as controlling the drug release process. Furthermore, the size of the nanoparticle on the film has a strong correlation with the size of the micelles in the precursor and the condition of the gelation process. It has been discovered that nanoparticle from 200 nm to 300 nm has shown the highest permeability for sublingual administration. In one example shown in work, the bioavailability of a low solubilize drug has been increased from 10% to 24% via sublingual administration of the film. The increasing of the bioavailability was thought to be associated with the enhancement of the diffusion process of the drug in the saliva layer above the mucosa membrane and the fact that the presents of the emulsifier help lose the rigid junction of the mucosa cells.

Keywords: oral dissolvable film, nano-suspension, nano-emulsion, bioavailability

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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: Simone F. Medeiros, Jessica M. Fonseca, Gizelda M. Alves, Danilo M. Santos, Sérgio P. Campana-Filho, Amilton M. Santos

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Stimuli responsive and biocompatible hydrogel nanoparticles have gained special attention as systems for potential applications in controlled release of drugs to improve their therapeutic efficacy while minimizing side effects. In this work, novel solid dispersions based on thermo- and pH-responsive poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate) hydrogel nanoparticles embedded in chitosan matrices were prepared via spray drying for controlled release of ketoprofen. Firstly, the hydrogel nanoparticles containing ketoprofen were prepared via precipitation polymerization and their stimuli-responsive behavior, thermal properties, chemical composition, encapsulation efficiency and morphology were characterized. Then, hydrogel nanoparticles with different particles size were embedded into chitosan matrices via spray-drying. Scanning electron microscopy (SEM) analyses were performed to investigate the particles size, dispersity and morphology. Finally, ketoprofen release profiles were studied as a function of pH and temperature. Chitosan/poly(NVCL-co-IA-co-EGDMA)-ketoprofen microparticles presented spherical shape, rough surface and pronounced agglomeration, indicating that hydrogels nanoparticles loaded with ketoprofen modified the surface of chitosan matrix. The maximum encapsulation efficiency of ketoprofen into hydrogel nanoparticles was 57.8% and the electrostatic interactions between amino groups from chitosan and carboxylic groups from hydrogel nanoparticles were able to control ketoprofen release. The hydrogel nanoparticles themselves were capable to retard the release of ketoprofen-loaded until 48h of in vitro release tests, while their incorporation into chitosan matrix achieved a maximum percentage of drug release of 45%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 10:7, and 69%, using a mass ratio of chitosan: poly(NVCL-co-IA-co-EGDMA equal to 5:2.

Keywords: hydrogel nanoparticles, poly(N-vinylcaprolactam-co-itaconic acid-co-ethylene- glycol dimethacrylate), chitosan, ketoprofen, spray-drying

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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: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Sperisa Distantina, Rieke Ulfha Noviyanti, Sri Sutriyani, Fadilah Fadilah, Mujtahid Kaavessina

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In this research, carrageenan extracted from seaweed Eucheuma cottonii was mixed with polyvinyl alcohol (PVA) and then crosslinked using glutaraldehyde (GA). The obtained hydrogel films were applied to control the drug release rate of paracetamol. The aim of this research was to develop a mathematical model that can be used to describe the mass transfer rate of paracetamol from the hydrogel film into buffer solution. The effect of weight ratio carrageenan-PVA (5: 0, 1: 0.5, 1: 1, 1: 2, 0: 5) on the parameters of the mathematical model was investigated also. Based on the experimental data, the proposed mathematical model could describe the mass transfer rate of paracetamol. The weight ratio of carrageenan-PVA greatly affected the amount of paracetamol absorbed in the hydrogel film and the mass transfer rate of paracetamol.

Keywords: carrageenan-PVA, crosslinking, glutaraldehyde, hydrogel, paracetamol, mass transfer

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Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

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Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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Authors: Yasmin Begum Mohammed

Abstract:

Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

Procedia PDF Downloads 295