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A strain of Aspergillus niger NRRL 337 degrade agro-industrial waste i.e wheat bran in solid state fermentation and produce esterase enzyme. Maximum enzyme activity 15.2 U/ml was produced after 72 h of incubation at 30˚C. The protein was partially purified by performing ammonium sulfate precipitation and immobilized metal ion chromatography (IMAC) technique. SDS-PAGE analysis showed molecular weight of esterase was 70 kDa. Effects of different nitrogrn and carbon sources with different concentrations were also studied. Partially purified enzyme was active at pH of 6.0 for up to 3 h and at temperature of 70˚C for 1 h. Ca2+, Mg2+, Na+1, and K+1 play an important role in increasing enzyme activity. The residual activity of esterase was decreased in the presence of organic solvents. SDS, β-mercaptoethanol, and DMSO are good inhibitors for esterase enzyme. Under these conditions, partially purified esterase with specific activity of 114.20 U/mg and 47.58 purification fold was obtained. The data achieved from this work are important in terms of heat stability and pH of esterase and giving a new enzyme source for industrial applications.

Stimuli responsive nanocarriers proved to be an efficient system in accurate diagnosis and targeted delivery of therapeutic moieties. Enzymes have been researched widely as successful targeting age...

This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA).Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application.Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index.The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.

Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0-t, and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

Snowballing levels of greenhouse gas emissions and concerns about climate change has led to an ongoing exploration of biofuels. Bioethanol can be obtained from wheat straw and can be readily available as clean fuel for combustion engines. Therefore, Wickerhamomyces anomalus yeast strain IHZ-26 was used to produce bioethanol from sugar solution obtained from enzymatic hydrolysis of wheat straw. Nineteen different fermentation media were used for this purpose in which carbon source employed was sugar solution obtained from enzymatic hydrolysis of wheat straw. Out of which, maximum bioethanol yield (1.09 g/L; p

Sustainable bio-renewable energy source is a need of an hour to meet the rising global energy demands. Efficient conversion of fermentable sugars by yeast into bioethanol from lingo-cellulosic biomass is one of the most important attribute. In order to get temperature and ethanol tolerant yeast strain, one hundred and seventy one soil samples were collected from adjacent areas of various sugar mills located in Punjab, Pakistan. Fifty six yeast strains were isolated and primarily screened for bioethanol production. Maximum bioethanol producing (3.07 g/L) yeast strain IHZ-26 was identified by sequencing of 18S rRNA ITS region and identified as a new strain of Wickerhamomyces anomalus which was assigned GenBank accession number KT883963. This strain demonstrated substantial tolerance to ethanol (25%) and temperature (50°C) and have the ability to significantly ferment several sugars i.e. glucose, fructose, mannose, maltose, xylose and lactose. To the best of our knowledge, this is first report of multi stress tolerant Wickerhamomyces anomalus from Pakistan. This yeast with these distinct characteristics can be employed in bioethanol industry for more viable and economical process.

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc.

Objective Biodegradable polymers are extensively used due to their efficient safety profiles. The aim of the current study was to fabricate, evaluate, and characterize biodegradable, biocompatible fluconazole (FLZ) loaded chitosan (CHS) chondroitin sulfate (CS) nanoparticles (NPs) for topical delivery. Polymers utilized in the formulation not only served as a carrier system but also aided in fighting with complex etiology of the disease due to their innate antifungal activities. Methods NPs were prepared by the complex coacervation method, then were optimized for various parameters and subsequently loaded into a cream. Results Scanning electron microscopic (SEM) analysis showed spherical morphology of the NPs. Prepared NPs showed an average particle size in the range of 350-450 nm and an encapsulation efficiency (EE) of 86%. The polydispersity index (PDI) was found to be 0.148 that showed a uniform distribution of NPs. Fourier transform infrared (FTIR) spectroscopy confirmed the absence of any electrostatic interaction between ingredients. In vitro drug release analyses exhibited a sustained release of the drug and higher antifungal activity than free FLZ. Ex vivo permeability and drug distribution in different skin layers ensured a site-specific delivery of the FLZ-NPs. As compared with free FLZ and other control groups, the prepared NPs also exhibited significantly higher antifungal activity against Candida albicans (p Conclusion It was concluded from the results that the FLZ-NPs laden cream could be a potential candidate for topical and site-specific delivery of the drug cargo for the potential treatment of fungal infections.

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non-exposure of active moieties to the harsh gastric environment and first-pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development.

Nanotechnology is a ground breaking and innovative field when combined with tissue engineering (TE) offers great versatility in enhancing cell adhesion, growth differentiation, proliferation, and synthesis of extracellular matrix. TE comprises several materials, that is, polymeric, metallic, and carbon-based structures. Polymeric nanomaterials can be used to fabricate biomaterials due to their unique properties like biodegradation and biocompatibility. Both natural and synthetic polymers are either combined or coated as nanomaterials to form nano surfaces, nanocomposite, nanofibers, and other nanostructures that can be used in TE. Selective polymers are discussed with their physiochemical properties and their utilization in nano-based TE. Various forms of scaffold can be utilized along with growth factors and polymeric nanomaterials to constitute required tissue. Fabrication of nanomaterials is done by electrospinning, self-assembly, and phase separation. Polymeric nanomaterials are used in both hard tissue (dental, bone, and craniofacial) and soft tissue (cardiac, neural, and cartilage) engineering.

Chronic wound infections have become a challenging problem due to escalating antibiotic resistance and lack of viable delivery approaches. Carvacrol (CAR) has been reported to be effective against multidrug resistant pathogens. In this study, CAR was formulated into a site-specific nanoparticle (NP) delivery system using poly(caprolactone) (PCL) to achieve a sustained antimicrobial effect at infection sites. These NPs were further incorporated into dissolving microneedles (MNs) to facilitate painless application and overcome the necrotic tissue barrier which hinders drug penetration into wound bed. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacteria, highlighting its potential for on-demand delivery. Moreover, encapsulation of CAR in PCL NPs resulted in 2–4 fold increase in its antimicrobial activity. Dermatokinetic studies revealed that CAR-PCL NPs-MNs were able to enhance skin retention of CAR after 24 h (83.8 ± 5.15%), compared to free CAR-MNs (7.3 ± 2.04%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo wound model. Hence, these findings have proven the concept that loading of CAR into this advanced MNs platform can lead to sustained antimicrobial effect at desired site and may provide a novel effective approach for treatment of infected wounds. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Background and Objectives Liraglutide, an analog of human glucagon-like peptide 1 (GLP-1), has been approved for the treatment of type 2 diabetes mellitus in Pakistan since 2016. It is a GLP-1 receptor agonist that has shown promising results in terms of not only glycemic control but also weight loss. Our study aimed to provide evidence regarding the safety and effectiveness of liraglutide in Pakistan and to look at the adherence rate and treatment satisfaction of patients using liraglutide. Methods This is an observational retrospective study that recruited patients who were treated with liraglutide. Data were collected at the first visit and follow-up. Morisky Green Levine Adherence Scale and Treatment Satisfaction Questionnaire for Medication (TSQM-9) were used for the determination of adherence and satisfaction with the treatment. Results A total of 70 patients were recruited in the study, The mean difference in weight, body mass index, glycated hemoglobin (HbA1C), systolic blood pressure, and diastolic blood pressure from baseline to follow-up was -5.36 kg, -2.14 kg/m2, -1.76%, -12.38 mmHg, and 5.55 mmHg, respectively. Nausea was the main side effect reported. TSQM-9 scores were compared from baseline, and it was found that patients are satisfied with the treatment and its effectiveness. Conclusions Our study has demonstrated the effectiveness of liraglutide as a monotherapy or combination therapy in the Pakistani population. Liraglutide led to reduction in HbA1C and weight. This is associated with high treatment satisfaction rate and adherence rate. Thus, liraglutide remains an effective though expensive treatment option in a country like Pakistan.

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal (PN) gel and evaluate its in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bi...

Biofilms present a challenge to wound healing and are among the most feared complications through the course of wound management. Carvacrol (CAR) has manifested its antibiofilm potential against multidrug resistant bacterial biofilms. Herein, infection responsive nanoparticles (NPs) of CAR were developed (particle size: 199 ± 8.21 nm and drug load: 1.35 mg/100 µL) and microneedle liquid injection systems (AdminPen®) of various specifications were investigated as delivery devices to achieve the higher concentrations (in contrast to the concentrations delivered through topical hydrogel) of NPs at the target site. The results exhibited an improved biosafety and antibiofilm activity of CAR after encapsulation into the NPs. Ex vivo skin insertion and dermatokinetic studies suggested that AdminPen® 1500 was the most suitable device, as compared to AdminPen® 777 and 1200. Finally, animal studies showed that AdminPen® 1500 delivered around 8.5 times higher concentrations of CAR in the form of NPs as compared with pure CAR from topically applied hydrogel. Moreover, 50% of the delivered NPs from the AdminPen® 1500 were retained at the site of application for 72 h, in contrast to the pure CAR from the hydrogel (5.2% only). Thus, AdminPen® assisted delivery of bacterial enzyme responsive NPs could be an effective approach for enhanced site-specific accumulation of CAR to potentially achieve the prolonged desired antibiofilm effect. However, further in vivo efficacy in a diseased model must now be investigated.

Aim: To formulate and evaluate a pH-responsive nanoparticle (NP)-based patch for efficient transdermal delivery of flurbiprofen against rheumatoid arthritis. Materials & methods: Nanoprecipitation technique was used for preparation of NPs and central composite design was employed for optimization purposes. Optimized NPs were loaded into the transdermal patch by the solvent evaporation method. Results: Prepared NPs exhibited an average size of 69 nm, while NPs loaded onto the transdermal patch showed sustained release and high permeation through the skin. In in vivo studies, the prepared carrier system elucidated high therapeutic potential in both acute and chronic inflammatory models as evident from the results of behavioral, radiological, histopathological and antioxidant analyses. Conclusion: The flurbiprofen-loaded pH-sensitive NP-based transdermal patch has the potential to manage rheumatoid arthritis effectively.

Voriconazole (VRC) is a broad-spectrum antifungal agent but possesses serious adverse effects systemically, which can be minimized by topical drug delivery. The goal of this project was to develop novel VRC-loaded polymeric nanoparticles to enhance the topical delivery in the form of film forming spray (FFS). The polymeric nanoparticles of VRC were prepared through Ionic gelation method and optimized using Design expert (free trial version 7) software. Optimized PNPs showed a spherical shape in nano-range. An extended release of VRC up to 24 hours from the optimized formulation followed a diffusion-based mechanism at skin pH (5.5). Ex vivo permeability and skin retentivity test confirmed the deposition of VRC in skin layers. The final formulation showed potential antifungal activity against Candida albicans and Aspergillus flavus. Non-irritant nature of film forming spray (FFS) was confirmed through histological study on the rabbit's skin. Hence, VRC-PNPs based FFS could be a potential candidate for treating topical fungal infections.

Biodegradable materials are extensively employed to design nanocarriers that mimic extracellular environment in arthritis. The aim of this study was to formulate and characterize biocompatible, biodegradable ketoprofen-loaded chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for transdermal applications. Polymers used in the design of nanocarriers are biodegradable and produce synergistic anti-inflammatory effect for the treatment of arthritis. For transdermal application, argan oil-based emulgel is utilized to impart viscosity to the formulation. Furthermore, naturally occurring argan oil synergizes anti-inflammatory effect of formulation and promotes skin penetration. CHS and CS form nanoparticles by polyelectrolyte complex formation or complex coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel. Employing this method, nanoparticles were formulated with particle size in the range of 300-500 nm. These nanocarriers entrapped ketoprofen and showed more than 76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within 72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion. Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of ketoprofen as compared to marketed gel (p 0.05). Nanocarriers prepared successfully delivered drug through transdermal route using natural ingredients. Graphical abstract ᅟ.

Vesicular drug delivery systems have gained wide attention in the field of nanotechnology. Among them proniosomes become the superior over other vesicular carriers. Proniosomes are dry formulations of water soluble nonionic surfactant coated carrier system which immediately forms niosomes upon hydration. They have the capability to overcome the instability problems associated with niosomes and liposomes and have the potential to improve solubility, bioavailability, and absorption of various drugs. Furthermore, they offer versatile drug delivery concept for enormous number of hydrophilic and hydrophobic drugs. They have the potential to deliver drugs effectively through different routes at specific site of action to achieve controlled release action and reduce toxic effects associated with drugs. This review discusses the general preparation techniques of proniosomes and mainly focus on the applications of proniosomes in drug delivery and targeting. Moreover, this review demonstrates critical appraisal of the literature for proniosomes. Additionally, this review extensively explains the potential of proniosomes in delivering drugs via different routes, such as oral, parenteral, dermal and transdermal, ocular, oral mucosal, vaginal, pulmonary, and intranasal. Finally, the comparison of proniosomes with niosomes manifests the clear distinction between them. Moreover, proniosomes need to be explored for proteins and peptide delivery and in the field of nutraceuticals and develop pilot plant scale up studies to investigate them in industrial set up.

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(&epsilon, caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 &plusmn, 3.15%), compared to free CAR-loaded hydrogel (0.85 &plusmn, 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Proniosomes offer excellent potential for improved drug delivery, through versatile routes, by overcoming the permeation barriers faced by several drugs. The study was aimed to develop a thiomer gel containing duloxetine proniosomes for the intranasal delivery, improving its bioavailability and brain delivery through olfactory system. Duloxetine-loaded proniosomes were optimized through Design-Expert Software, prepared by coacervation phase separation method and then characterized in vitro for different vesicle features, and permeation enhancement potential using various techniques. The formulation F2, out of all the trials, fulfilled the maximum requisite of highest entrapment efficiency (76.21 ± 1.24%) and minimum vesicle size (223.91 ± 11.07 nm). The F2 was embedded in thiolated chitosan gel rendering it mucoadhesive and further characterized. The in vitro release showed a sustained drug release from the mucoadhesive proniosomal gel with only 54% drug release as compared to that of 71% from proniosome over 8 h, following Higuchi drug release model. Ex vivo permeation studies showed the enhancement ratio for the mucoadhesive proniosomal gel to be 1.86-fold greater than proniosomes, indicating a significant improvement in transmucosal permeation. The results suggest that incorporation of proniosomes into thiolated gel can significantly improve its mucoadhesion and retention time in the nasal cavity for providing a sustained drug release. Thus, gel formulation could be considered as a promising approach for efficient intranasal drug delivery of duloxetine. Graphical Abstract.

Nanotechnology based drug delivery systems are employed to overcome the hitches associated with conventional therapies. The current study aimed to develop biopolymeric nanoparticles of artemether for transdermal delivery as an alternative to oral route's hindrances. Biopolymers; chitosan and chondroitin sulfate were used to prepare and optimize artemether-loaded nanoparticles through ionic gelation method and loaded in a transdermal patch. Artemether loaded nanoparticles were having particle size 234 nm, poly dispersity index 0.2 and zeta potential 30 mV. Encapsulation efficiency was found to be 83 ± 0.28%, percentage yield 71 ± 0.4% and loading capacity was 23 ± 0.59%. SEM showed spherical shape and uniform distribution of nanoparticles. FTIR spectroscopy confirmed the compatibility among components of nanoparticles. XRD analysis showed conversion of crystalline artemether into amorphous form in nanoparticles. Release studies revealed that artemether was released from nanoparticles through diffusion-controlled mechanism. Ex vivo permeability study showed enhanced permeability of drug from the transdermal patch having permeation enhancer (olive oil). Skin integrity, verified through FTIR, was maintained after applying the transdermal patch. Fluorescence microscopy of skin displayed uniform permeation of nanoparticles. Transdermal patch showed no change in physical appearance up to 6 months. Thus, artemether loaded biopolymeric nanoparticles were successfully prepared and loaded magnificently into the transdermal patch.

Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.Particles with an average size of 25-40 nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.

Various biodegradable polymers have been extensively used for different biomedical applications since the start of 21st century. Use of bioresorbable polymers such as polylactide and polyglycolide (PGA) is preferred due their properties of complete resorbability in vivo, although the time frame can be different depending on the purpose of use. Polylactide or polylactic acid (PLA) is obtained from plant or microbial sources as well as being synthetically prepared in laboratories and various modifications are possible. The ease of modifications in their properties using heat, adding fillers, and plasticizers and copolymerization with other polymers are additional advantages of PLA. It is extensively applied in tissue engineering, tumor treatment, imaging and diagnosis, immunization, DNA, and gene and drug delivery systems. It is need of time to provide a comprehensive review of PLA applications in biomedical field especially in biomedical engineering. This chapter will serve this purpose and includes a discussion of PLA synthesis and modifications to alter its properties for various applications. The applications are focused on the research done over the past two decades.

This study presents sustained releasemicroencapsulation of Diltiazem HCL. Its in-vitro dissolution study in phosphate buffer pH 7.4 as dissolution medium and in vivo behaviour in animal subjects. The microcapsules were prepared using polymers Ethocel 7P and Ethocel 7FP at two different drug to polymer (D: P) ratios i.e. 1:5 and 1:10 and the effect of concentration was observed on drug release behaviour. The prepared microcapsules were evaluated for different physical characteristics i.e. Bulk density, Tap density, Compressibility index, Hausner’s ratio and Angle of repose. Characterization of the developed microcapsules was carried out using Differential Scanning Calorimetery and Fourier Transform Infrared Spectroscopy while Scanning Electron Microscopy was performed to observe the morphology of the microcapsules. Model dependent and in dependent approaches were used to find out the drug transport mechanism and to compare the drug release profiles with standard formulation respectively. All the formulations show anomalous, non-Fickian diffusion mechanism and the data was best fitted in Korsmeyer’sPeppas equation. While carrying out in vivo studies, simple and rapid HPLC methods were developed which revealed optimum serum concentration (Cmax) levels for the developed microcapsules predicting least chances of side or adverse effects.

Nanotechnology has burgeoned over last decade exploring varieties of novel applications in all areas of science and technology. Utilisation of bio-friendly polymers for engineering nanostructures (NS) improves safety and efficacy in drug delivery. Biopolymers not merely employed for fabricating drug carriers but also leveraged for surface functionalisation of other NS to impart bio-mimicking properties. Biopolymer functionalised NS garnered researcher's attention because of their potential to enhance skin permeability of drug cargo. Biopolymers, i.e. cell-penetrating peptides (CPP), chitosan and hyaluronic acid not only enhance skin permeability but also add multiple functions due to their intrinsic biomimetic properties. This multifunctional drug delivery system is a promising tool to achieve skin delivery of large number of therapeutic agents. In this review, functionalisation of NS with biopolymers particularly polysaccharides and polypeptides is discussed in detail. In particular, applications of these functionalised NS for TDDS is elaborated. Moreover, this review provides framework for elaborating importance of functionalisation of NS to enhance skin permeability and depicts advantages of biopolymers to construct more biocompatible carriers for drug cargos.

The present work aimed to synthesize drug loaded nanostructured lipid carriers (NLCs) for treatment of cutaneous leishmaniasis (CL). Topical drug delivery is a favourable option in treatment of localized cutaneous leishmaniasis (LCL) and is always considered superior over systemic therapy and intralesional antimony injections. Curcumin was chosen as model antileishmanial drug and drug loaded NLCs (Cur-NLCs) were prepared by hot homogenization followed by probe sonication technique. Prepared Cur-NLCs were characterized for particle size (312 ± 1.89 nm), encapsulation efficiency (88 ± 2.45%), zeta potential (−38 ± 0.93 mV) and Polydispersity index (0.305 ± 0.17). Blank and drug loaded NLCs were characterized for morphology using scanning electron microscopy (SEM) and FTIR was done to study any interaction between excipients. Cur-NLCs were also characterized for in vitro drug release and ex vivo skin permeation and deposition study. Moreover, targeting potential to macrophages and deeper skin layers was evaluated using fluorescence microscopy. A higher drug deposition in stratum corneum and deeper skin layers was achieved with Cur-NLCs gel as compared to curcumin reference gel (RG). The in vitro antileishmanial assay against promastigotes and axenic amastigote like cells (AALCs) demonstrated Cur-NLCs (IC50 values of 105 μg/ml and 190 μg/ml against promastigotes and AALCs respectively) to be superior as compared to plain curcumin solution (IC50 values of 165 μg/ml and 243 μg/ml against promastigotes and AALCs respectively). Results suggested that topical application of drug loaded NLCs can lead to targeted delivery of antileishmanial drugs to site of action i.e., infected macrophages residing in deeper skin layers.

The aim of this study was to formulate and evaluate polymeric tablets of Ketoprofen for the release rate, and mechanism. Formulations with different types and grades of Ethyl Cellulose Ether derivatives were prepared in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3). These formulations were compressed into tablets using the direct compression method. They were examined for the physical properties and appearance. Tablet dimensional tests i.e., (thickness, diameter) and QC tests (hardness, friability, and disintegration) were performed according to the USP methods. Invitro dissolution was performed. In order to analyze the drug release kinetics from each of the prepared matrices, five standard mathematical models were applied to the release data. The study showed that in case of tablets containing Ethocel premium polymers of 7, 10, and 100 grades show approximately 90-98% release of the drug from tablet in 24 hours compared to the Ethocel FP premium of 7, 10, and 100 which showed less release in 24 hours following nearly zero order kinetics.

The ciliate, Vorticella microstoma, showed tolerance against Cd2+ (22 μg/mL), Cu2+ (22 μg/mL), Ni2+ (17 μg/mL), and Hg2+ (16 μg/mL). The metal ions slowed down the growth of the ciliate as compared to the culture grown without metal stress. The decrease in cell population was 60% for Cd2+, 49% for Cu2+, 35% for Ni2+, and 49% for Hg2+ after 8 days of metal stress. The order of resistance to heavy metal, in terms of reduction in the cellular population, was Ni2+ < Hg2+ = Cu2+ < Cd2+. Metal-uptake capability of the ciliate was worked out for its potential use as bioremediator of wastewater. V. microstoma decreased 72% of Cd2+, 82% of Cu2+, 80% of Ni2+, and 74% of Hg2+ from the medium after 96 h of incubation. V. microstoma was also able to remove 73% of Cd2+, 80% of Cu2+, 83% of Ni2+, and 76% of Hg2+ from the industrial wastewater after 6 days of incubation at room temperature. The multiple heavy metal uptake ability of V. microstoma can be exploited for metal detoxification and environmental clean-up operations. © 2010 American Institute of Chemical Engineers Environ Prog, 2010

Metallo-elements have strong affinity for sulfhydryl group (-SH) of glutathione (GSH) present in tissues. It is very important and interesting to study the reaction of gallium nitrate and glutathione as biomarker of glutathione role in detoxification and conjugation in whole blood components (plasma and cytosolic fraction). The effect of gallium nitrate different concentrations was examined on GSH present in whole blood components. Decrease in GSH level was dependant on gallium nitrate concentration. The decrease in GSH level of whole blood components was more prominent with the time of incubation of gallium nitrate. Decrease in the concentration of reduced glutathione may be due to the interaction of reduce glutathione and gallium nitrate to form oxidized glutathione (GSSG) or gallium-glutathione complex. This change in GSH metabolic status provides information regarding the role of GSH in detoxification of gallium nitrate. The effect of gallium metal on glutathione in blood components was discussed in this study in in vitro condition as a model for in vivo condition. Key words: Gallium nitrate, reduced glutathione (GSH), whole blood, plasma, cytosolic fraction (CF), oxidized glutathione (GSSG), Di-thiobis- dinitro-benzoic acid (DTNB).

Purpose : To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents. Methods : The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulose were also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release models Results : As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion. Conclusion : Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug. Keywords : Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled release

The objective of the study was to formulate and evaluate sustained release polymeric tablets of ketoprofen for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with three different types of newly synthesized polymers and one grade of ethyl cellulose ether derivatives (FP100 premium) in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3) were compressed into tablets using the direct compression method. They were examined for their physical properties and appearance. Tablets dimensional tests (thickness, diameter) and Q.C tests (hardness, friability, disintegration) were performed according to the USP methods. For in vitro drug release studies of Ketoprofen controlled release (CR) tablets, the USP Method-1 (Rotating Basket Method) was used with Pharma test dissolution apparatus (D-63512 Hainburg, Germany). The medium used for dissolution was phosphate buffer having a pH of 7.4 kept at constant temperature of 37±1°C. In order to analyze the drug release kinetics from each of the prepared matrices, five different mathematical models were applied to the release data including zero order kinetics, first order kinetics, Higuchi kinetics, Hixson Crowell kinetics and Korsmeyer Peppas equations were applied to the release data. The results obtained from different parameters showed that polymers: Polyglycolide, PGA-co-caprolactone, PGA-co-pentadecalactone and Ethocel FP100 premium can be used successfully in order to develop directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen. Particle size of polymer is a determining factor in controlling the release of ketoprofen from tablets. Ethocel standard FP100 polymers extend the release rates of drug more efficiently than the conventional granular form of the other three polymers. Further, the three new polymers and Ethocel FP100 could efficiently extend the release of the drugs as compared to the reference conventional formulation. Key words: Polymers, Ketoprofen, controlled-release preparations.

Lead has been found to have the ability to interfere in the metabolism and biological activities of many proteins. It has also been found that metalloelements have strong affinity for sulfhydryl (-SH) groups in biological molecules including glutathione (GSH) in tissues. Because of these facts, it was of interest to investigate further the interaction of lead acetate [Pb (CH 3 COO) 2 ] with GSH as a biomarker of toxicity and the role of GSH in the detoxification and conjugation processes in whole blood components. Effects of different concentrations of Pb(CH 3 COO) 2 on the level of reduced GSH in whole blood components (plasma and cytosolic fraction) were examined. GSH depletion in whole blood components was lead acetate concentration dependent. Depleted GSH level was however more pronounced with time. These findings show that changes in the GSH status produced by Pb(CH 3 COO) 2 could be due to either by adduct (Pb-SG) formation or by increased production of oxidized glutathione (2GSH Pb+2 GSSG). This change in GSH metabolic status provides information regarding the mechanism of toxicity of Pb(CH 3 COO) 2 . These findings are therefore important for the rational design of antidote against the prevention of lead induced toxicity. Key words : Lead acetate, glutathione (GSH), dithiobisdinitrobenzoic acid (DTNB), plasma and cytosolic fraction (CF).

The objective of this study was to develop directly compressed oral controlled-release ibuprofen matrix tablets containing hydrophobic polymer (Ethocel®) of different viscosity gardes (Ethocel®standard 7P, 7FP, 10P, 10FP 100P and 100FP). As ibuprofen like other non-steroidal anti-inflammatory drugs has dosage frequency and severe gastrointestinal tract (GIT) complications and patient non-compliance, so to avoid these problems, controlled release matrices were developed. Before development of matrix tablets, pre-formulation studies were performed for the determination of physicochemical interaction between polymer, drug and co-excipients, using differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) and no interaction was found. Controlled-release matrix tablets were formulated by direct compression method. Effect of partial replacement of lactose by different co-excipients such as HPMC K100M, starch and CMC on the release of drug was also studied. The tablets were subjected to different physicochemical, dimensional and quality controlled tests, such as drug content, weight variations, friability, hardness, thickness and diameter, all these tests were within United Stated Pharmacopoeia (USP) range. The in vitro release profile in phosphate buffer (pH 7.4) for all formulations containing polymer and co-excipients was compared with a formulation developed without polymer and co-excipients for 24 h. Different kinetics models were used, such as first-order equation, zero-order equation, Higuachi equation, Hixon Crowel’s equation and Korsmeyer-Peppas to study and investigate the release mechanism. It was concluded that formulations containing different grades of ethylcellulose polymer showed prolonged release for 6 to 18 h, but the formulation containing polymer Ethocel® standard FP7 premium without co-excipient showed controlled release for 24 h, which can be used to develop controlled release matrices of ibuprofen with optimum release kinetics. All those formulations containing co-excipients showed enhanced release rate. Key words: Ethocel® standard FP premium, Ethocel® standard premium, ibuprofen, matrix tablets, co-excipients, controlled release.

A ciliate protozoan, Euplotes mutabilis, isolated from heavy metal laden industrial wastewater, has been shown to tolerate multiple heavy metals thus suggesting its significance in bioremediation of industrial effluents. This ciliate tolerated Zn(2+) up to 33 microg/mL, Cd(2+) up to 22 microg/mL and Ni(2+) up to 18 microg/mL. The ciliate could uptake 85% Zn(2+), 84% of Cd(2+) and 87% of Ni(2+) after 96 h of inoculation of growth medium containing 10 microg/mL of Zn(2+) and 5 microg/mL of Cd(2+) and Ni(2+), with actively growing ciliates. After 6 days of incubation the ciliate removed 87% Cd(2+), 92% Ni(2+), and 93% Zn(2+) from the wastewater. The heavy metal uptake capability of Euplotes mutabilis may be employed for metal detoxification operations.