Basant Malik

Microfold-cell targeted surface engineered polymeric nanoparticles for oral immunization

Present work was envisaged to develop novel M-cell targeted polymeric particles that are capable of protecting the antigen from harsh gastric conditions. Ulex europaeus agglutinin (UEA-1) lectin was anchored for selective delivery of antigen to gut-associated lymphoid tissue (GALT). In the present investigation, chitosan nanoparticles were prepared by ionic gelation followed by antigen (bovine serum albumin, BSA) adsorption. Developed nanoparticles were further coated by UEA-1 lectin conjugated alginate and characterized for size, shape, zeta-potential, entrapment efficiency, and in vitro release. The immunological response of the developed system were performed in Balb/c mice and compared with aluminium hydroxide gel-based conventional vaccine. Results indicated that immunization with UEA-1 lectin conjugated alginate-coated particles induces efficient systemic as well as mucosal immune responses against BSA compared to other formulations. Aluminium-based vaccine dominated throughout the study, while failed in case of mucosal antibody. Additionally, IgG1 and IgG2a isotypes were determined to confirm the TH1/TH2 mixed immune response. The developed formulation exhibited superior systemic response along with dominating mucosal immunity. These data demonstrate the potential of UEA-alginate-coated nanoparticles as effective delivery system via oral route.

Development and characterization of nano-fiber patch for the treatment of glaucoma.

In the present work polymeric nano-fiber patches was developed for the effective treatment of glaucoma using timolol maleate and dorzolamide hydrochloride as model drugs. The nano-fibers were prepared by electrospinning technique and were characterized on the basis of fiber diameter, morphology, entrapment efficiency, mucoadhesive strength, and drug release behavior, etc. Final formulations were inserted in the cul-de-sac of glaucoma induced rabbits and the efficacy of the formulation was evaluated. The results clearly indicated the potential of the developed formulation for occur drug delivery. There was a significant fall in the intraocular pressure compared to commercial eye drops.

Development and characterization of niosomal gel for topical delivery of benzoyl peroxide.

Abstract Benzoyl peroxide (BPO) is generally considered as first line treatment against acne. Low water solubility and formation of larger clusters and limited skin permeation upon topical application necessitates the application of high amount of drug for desired action which leads to induction of skin irritation. In the present study, we developed BPO-loaded niosomal formulation to improve its permeation through skin. The niosomes were further loaded in the carbopol gel to improve contact time. The results of the skin permeation study, skin retention study revealed that niosomes can effectively improve the drug permeation through skin. Application of niosomal gel significantly reduced the bacterial load after a treatment of four days. This reduction in bacterial load was further resulted in a significant reduction in the inflammation with minimal skin irritation compared with plain drug and the plain niosomal formulation.

Development and characterization of guar gum nanoparticles for oral immunization against tuberculosis.

Abstract The main aim of this study was to develop an effective carrier system containing Ag85A-loaded guar gum nanoparticles for oral vaccination against tuberculosis. Nanoparticles were prepared by Nanoprecipitation method. The developed particles with mean diameter 895.5 ± 14.73 nm and high antigen entrapment seem to be optimum for oral vaccine delivery. The acid protection assay, Peyer’s patch uptake study and in-vitro antigen study confirmed that the developed formulations can protect the antigen from harsh gastric environment and can safely deliver the antigen to the intestinal region. In vivo studies data indicated that the developed nanocarriers can induce a strong mucosal as well as systemic immune response. Therefore, the experimental evidence suggests that guar-gum nanoparticle findings indicated that the guar gum nanoparticles can be utilized for safe and effective vaccine delivery via oral route.

Development and characterization of oleic acid vesicles for the topical delivery of fluconazole

Fatty acids have been widely used as adjuvant, vehicles in drug delivery viz penetration enhancers in topical delivery and in polymeric micelles to provide sustained release. However, the present investigation aims at exploring the potential of fatty acid vesicles for the topical delivery of fluconazole. Vesicles were prepared by film hydration method using oleic acid as a fatty acid principal component. Developed vesicles were characterized for size, size distribution, shape, in vitro release, pH dependent and storage stability, skin irritation study, and ex-vivo skin permeation. Penetration behavior of vesicles was further evaluated and elucidated using confocal microscopic study. Optical microscopy and TEM studies confirmed vesicular dispersion of fatty acid. The vesicles possessed higher entrapment efficiency (44.11%) with optimum vesicle size and homogeneity in regard to size distribution (PDI = 0.234 ± 0.016) at 7:3 oleic acid-to-fluconazole ratio. In vitro drug release study suggested sustained release of drug from the vesicles. The release pattern followed Higuchian kinetics. The vesicles were fairly stable at refrigerated conditions. Ex-vivo skin permeation and confocal microscopic studies suggested that oleic acid vesicles penetrate the stratum corneum and retain the drug accumulated in the epidermal part of the skin. On the basis of sustained release behavior and skin retention it can be inferred that oleic acid vesicles can serve as a potential carrier for the topical localized delivery of bioactives.

Development and characterization of spray-dried porous nanoaggregates for pulmonary delivery of anti-tubercular drugs

Abstract Tuberculosis, MTB or tubercle bacillus (TB) is a lethal, infectious disease mainly caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. In this study, guar gum-based porous nanoaggregates were formulated by precipitation technique with two frontline antitubercular drugs, i.e. isoniazid and rifampicin. The formulations were optimized on the basis of various evaluation parameters such as morphology, density, entrapment efficiency and in vitro drug release. The optimized formulations were administered by inhalable route to Wistar rats for the evaluation of drugs in different organs (lungs, liver and kidneys). High drug encapsulation efficiency was achieved in guar gum porous nanoaggregates, ranging from 50% to 60%. A single pulmonary dose resulted in therapeutic drug concentrations of 30%–50% in the lungs and in other organs (less than 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs. Furthermore, the formulation showed sustained drug release pattern, which could be beneficial for reducing the drug dose or frequency of dosing, thus helpful in improving patient compliance.

Development, Optimization & Evaluation of Porous Chitosan Scaffold Formulation of Gliclazide for the Treatment of Type-2 Diabetes Mellitus

This article characterizes the activities required to launch a new pharmaceutical molecule into the market, summarizes studies that have attempted to pinpoint the research and development costs incurred per approved new molecule, and analyzes the various critiques levied against published R&D cost estimates. It finds that by any reckoning, R&D costs per approved molecule have risen sharply over time, most likely at a rate of approximately 7 percent per year after stripping out the effects of general economic inflation.A is a newer NSAID, used in treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Aceclofenac has shorter biological half-life around 4 h which makes it suitable for modified release to improve bioavailability and to reduce dosing frequency. Present work was aimed to develop and evaluate aceclofenac modified release (Triple Layer Tablet) TLT following direct compression technique using natural and synthetic polymers. Aceclofenac TLT containing immediate-releaselayer (IM) as first layer, controlled-release-layer (CR) as second layer and ethyl cellulose layer as barrier-layer (BL) were prepared. IM was optimized by D-optimal design where 16 formulations (IM1 – IM16) were developed by using super disintegrating agents like mannitol and SSG. CR was optimized by 32 full factorial design and 9 batches (CN1–CN9 & CS1–CS9) were developed using natural and synthetic polymers like guar gum, xanthan gum and HPMC K100 CR, HPMC K100 LVCR respectively. Drugpolymers compatibility was evaluated by Infrared spectroscopy, where all compositions were found compatible without any interaction. All formulations were evaluated for various post-compression parameters like disintegration time (DT), swelling index, hardness, friability and weight variation etc., and results were found in desirable range. IM and CR formulations were evaluated for drug release behavior in pH 6.8 phosphate buffer and best release compositions among batches were chosen to prepare TLT with BL to modify the release. Among IM formulations least DT was found in IF9 with 90.86% drug release in 10 min 21 sec so, IF9 was claimed as best composition. Among CR formulations the best compositions found were CN3 and CS6 with Time at 47.38 % and 26.42% drug release around 8 h respectively and, were then developed as triple layered tablets with IF9 where drug release was extended up to 24 h.H compounds have received considerable attention owing to their variety of biological activities, especially as inhibitors of PDE5 extracted from human platelets, HIV-1 reverse transcriptase, human EPK2, cyclin-dependent kinas. Also, heterocyclic nitrogen compounds are indispensable structural units for medicinal chemists and used as antibiotics, anthelmintics, antiviral, antidepressant, and anti-inflammatory. In view of these observations we evaluate some new poly hetero cyclic compounds which were previously synthesized according to for their analgesic, anti-inflammatory and anti-microbial activities in comparison to some reference drugs. Pyrimidines present an interesting group of compounds many of which possess wide-spread pharmacological properties such as antidepressant, antimicrobial, anticancer, and anticonvulsant activitiesM drugs combination is a promising strategy in biomedical fields, such as cancer chemotherapy, tissue engineering. The multi-drug system enables to be delivered with multiply targets and exhibits the additive or synergistic effects of drugs. However, the specific distinct drug release kinetics of the multiply drugs are required to meet the clinical needs, especially in the combined therapy of tissue regeneration and tumor chemotherapy. In order to deliver the individual drug at optimal dosages, the release behaviors of each drug in multi-drug systems should be controlled independently. Therefore, two kinds of nanoparicles with core-shell structure (PVP/PLGA and PCL/PLGA) were fabricated by coaxial electrospray in this paper. Each kind of nanoparticles can both encapsulate the hydrophilic rhodamine B and hydrophobic naproxen in one single step efficiently. The monodisperse size distribution as well as the desired core-shell structure was observed. These two multi-drug systems with dual drug loaded exhibited different distinct release profiles, attributing to the distinct core-shell structures of nanoparticles and the difference of two drugs in hydrophilic properties. Meanwhile, the release profiles of encapsulated drugs with different amount were investigated as well. The drug release behaviors were dominated by the following processes: water penetration, surface drug release, outer drug diffusion with shell polymer erosion, inner drug diffusion and nanoparticle collapse. The results suggested that the distinct release kinetics of multiply drugs fabricated by coaxial electrospray can be obtained and tuned to fulfill the clinical requirement in combination therapy.Aspirin suppositories are in commercial use, suffer with side effects such as irritation, burning sensation, rectal hemorrhage. The aim of the present work is to formulate aspirin nanoparticles loaded suppositories and to perform In vitro investigation for the prepared suppositories. Initially aspirin-chitosan nanoparticles were prepared by ionic gelation method and the nanoparticles evaluated for different In vitro evaluation studies; based on results the best formulation was selected and in order to know the diffusion efficiency, different compositions of aspirin glycerogelatin suppositories were prepared and subjected to various In vitro evaluation studies and best composition was selected. From the previously performed evaluation studies best formulation from aspirin nanoparticles incorporated in to selected glycerol gelatin bases and evaluated for In vitro characteristics. The results indicates that formulation Fa9 Aspirin nanoparticles were proved to be best formulation with 88.3±1.1 % of drug release at the end of 24hr, with zero drug release. In vitro characterization performed for aspirin suppositories indicates that Fs2, Fs4, Fs9 and Fa11 was proved to be best composition with highest percentage of drug release at the end of 60 minutes with 98.06±1, 99.3±0.45, 97.6±1.8 and 97±1 drug release and other characteristic studies performed indicates that all formulation are ideal characteristics. Previously selected bases composition used for the loading of nanoparticles based on displacement value results indicates that drug release appears with a lag phase initially and controlled for a period of 24hr.Orally dissolving tablets (ODT) provides a patient compliance solution for patients swallowing difficulties. Foam granulation is a newer technique that promises better distribution of the granulating system and better properties of the produced tablets. Aceclofenac (anti-inflammatory and analgesic) was selected as the model drug. The poor hydrophilicity of the drug results in variable dissolution rate and poor bioavailability. In this study, we tried to prepare aceclofenac ODT using the newer technique and various types of disintegrants, glidants, and lubricants. The resulted tablets were evaluated for hardness, friability, weight variation, in vitro disintegration time, and wetting time. All the formulation showed acceptable disintegration time. It was concluded that the prepared aceclofenac ODT by foam granulation technique using selective range of excipients can provide a dosage form with better patient compliance and effective therapy.

Development of Transmucosal Patch Using Nanofibers

Abstract: In the present work we have attempted to develop a novel transmucosal patch of diclofenac sodium using electrospun polycaprolactone (PCL) nanofibers. PCL nanofibers were prepared by electrospinning techniques using different polymer concentrations. Nanofibers formulations were characterized by SEM, FTIR, drug loading, and in-vitro release study using Franz diffusion cell. Studies revealed the nanofibers fabricated from 13% PCL were fracture-free, non-beaded, and ultrafine with 120 nm diameter. Release studies demonstrated the sustained release behavior of PCL nanofibers. Nanofibers can be exploited for transmucosal drug delivery of NSAID with improved therapeutic efficacy.

Are the anatomical sites for vaccine administration selected judiciously

Route of vaccine administration plays an important role in the development of immune response. Antigen administered via different anatomical sites interacts with diverse subsets of antigen presenting cells. Diverse population of antigen presenting cells directs a drastically different immune response. Initially, the recommended routes for vaccine administration were also selected on the basis of clinical trials conducted for the drug molecules. However, physicochemical and pharmaceutical behaviors of proteins (antigens) and chemical compounds are entirely different. Most of the commercial vaccines are injected in the arm or in the scapular region (deltoid muscle). Vaccine administered to these conventional anatomical sites has failed to induce desired immune response due to lack of optimum level of antigen presenting cells. In this review, we have discussed the importance of the selection of anatomical sites for vaccine administration. Mere selection of an optimum site for vaccine administration may drastically change the immune response of the current marketed formulations without any alteration in their existing production plans.

Development of pH responsive novel emulsion adjuvant for oral immunization and in vivo evaluation

The present work has been envisaged to develop a pH responsive multiple emulsion (W/O/W) adjuvant for successful antigen delivery via oral route. The formulation was prepared by double emulsion technique using squalene as oil phase and a combination of antigens and Quil A as internal aqueous phase. Squalene emulsion (O/W) adjuvants are well accepted for parenteral administration. Instead of using conventional surfactants, Quil A was incorporated in the internal aqueous compartment for the first time. The microscopic analysis confirmed the formation of the W/O/W multiple emulsions with globule diameter ranging from 7 to 12 μm. Considerably, addition of Quil A resulted in marked improvement in both in vitro stability and immune response. Furthermore, addition of pectin to the external aqueous phase resulted in improved in vitro stability. A formulation with gel like structure was formed when pectin was used as stabilizer and also accounted with a significant increase in viscosity (from 275.3 cP to 330.4 cP) in the simulated gastric fluid, which reverts back to 290.2 cP after exposure to simulated intestinal fluid. Induction of strong mucosal and systemic immune response suggested that the developed formulation could be useful for the delivery of multiple biomolecules via oral route.