Amit Bhatia

Design, development and optimization of nimesulide-loaded liposomal systems for topical application.

Nimesulide, a non-steroidal anti-inflammatory drug, was incorporated into multilamellar liposomes to improve its performance on topical administration. The drug was loaded onto liposomes employing thin film hydration technique. Various process and formulation variables were investigated to obtain the liposomal products of desired quality. Liposomes were monitored for percent drug entrapment, after separating the unentrapped drug by mini column centrifugation, for vesicular properties (such as size distribution profile, morphological attributes and agglomeration tendency), drug diffused through synthetic semipermeable membrane, and drug leakage. Systematic optimization studies were carried out using 3(2) factorial design to select the optimized liposomal composition with reference to percent drug entrapment, drug diffusion and leakage. The optimized batch of liposomes was subjected to drug permeation and drug retention studies employing rat skin and human cadaver skin. In comparison to methanolic solution of pure nimesulide, liposomal formulations were found to retain higher amounts of nimesulide in the skin. Anti-inflammatory studies, using carragenan-induced rat paw edema model, indicated significantly better performance of liposomally entrapped nimesulide in comparison to the marketed gel formulation and the Carbopol gel containing nimesulide.

Tamoxifen-loaded lecithin organogel (LO) for topical application: Development, optimization and characterization.

Lecithin organogels (LOs) are semi-solid systems with immobilized organic liquid phase in 3-D network of self-assembled gelators. This paper attempts to study the various attributes of LOs, starting from selection of materials, optimization of influential components to LO specific characterization. After screening of various components (type of gelators, organic and aqueous phase) and construction of phase diagrams, a D-optimal mixture design was employed for the systematic optimization of the LO composition. The response surface plots were constructed for various response variables, viz. viscosity, gel strength, spreadability and consistency index. The optimized LO composition was searched employing overlay plots. Subsequent validation of the optimization study employing check-point formulations, located using grid search, indicated high degree of prognostic ability of the experimental design. The optimized formulation was characterized for morphology, drug content, rheology, spreadability, pH, phase transition temperatures, and physical and chemical stability. The outcomes of the study were interesting showing high dependence of LO attributes on the type and amount of phospholipid, Poloxamer™, auxillary gelators and organic solvent. The optimized LO was found to be quite stable, easily applicable and biocompatible. The findings of the study can be utilized for the development of LO systems of other drugs for the safer and effective topical delivery.

Improved therapeutic performance of dithranol against psoriasis employing systematically optimized nanoemulsomes

Despite marked antipsoriatic activity of dithranol (anthralin), the drug is quite infrequently employed in therapeutic practice owing to its strong propensity to cause skin problems like irritation, erythema and peeling, and potential formulation problems like photolability and high lipophilicity. Accordingly, it was planned to systematically formulate optimized dithranol-loaded emulsomes with enhanced biocompatibility, efficacy and stability. Emulsomes were prepared by a thin film hydration technique and optimized for composition using formulation by design (FbD). The optimized dithranol-loaded emulsomes were found to substantially enhance the antipsoriatic activity on a mouse-tail model vis-à-vis marketed product. Also, the selected composition offered enhanced drug permeation and marked skin retention. The formulation was found to be quite non-irritant, stable and biocompatible in comparison to the marketed product. The present findings establish the usefulness of lipid-based colloidal carriers to increase the stability, and enhance the efficacy and patient compliance of an age-old irritant dithranol.

C60-fullerenes for delivery of docetaxel to breast cancer cells: A promising approach for enhanced efficacy and better pharmacokinetic profile.

Docetaxel has always attracted the researchers owing to its promises and challenges. Despite marked efficacy, concerns like poor aqueous solubility, lower bioavailability, poor tissue penetration and dose related side-effects offer further scope of research on docetaxel. The present study aims to explore the potential of C60-fullerenes in the delivery of docetaxel to cancerous cells. C60-fullerenes were carboxylated, acylated and conjugated with the drug. The chemical processes were monitored by UV, FT-IR and NMR spectroscopy. The conjugate was further characterized for drug loading, micromeritics, drug release, morphology and evaluated for in-vitro cytotoxicity, haemolysis and in-vivo pharmacokinetic profile. The developed nanoconstruct was able to enhance the bioavailability of docetaxel by 4.2 times and decrease the drug clearance by 50%. The developed system was able to control the drug release and was found to be compatible with erythrocytes. The cytotoxic potential on studied MCF-7 and MDA-MB231 cell lines was also enhanced by many folds, indicating marked promise in efficacy enhancement and dose reduction. The present findings are encouraging and offer a technique to enhance the delivery and efficacy potential of anticancer agents, especially belonging to BCS class IV.

Design and evaluation of flexible membrane vesicles (FMVs) for enhanced topical delivery of capsaicin

Capsaicin, extracted from the fruits of Capsicum, is a powerful local stimulant with strong rubifacient action, devoid of vesication. Topical use of capsaicin is quite common in the treatment of various pain-associated musculo-skeletal disorders, itching and neuropathy. Despite its high pharmacodynamic potential, the patient compliance to the drug is reported to be poor owing to multiple skin problems like irritation, burning sensation, and erythma. The present study targets the encasement of drug in the interiors of flexible membrane vesicles (FMVs), as these are reported to have better penetration in the deeper layers of skin, thus leading to enhanced localization of drug and consequently, decreased skin irritation. Multilamellar drug-loaded FMVs, prepared by thin-film hydration were evaluated for their efficacy in vitro and in vivo. When compared with conventional liposomes, the formulated FMVs showed higher skin retention during ex vivo permeation studies employing LACA mice skin, higher analgesic potential using radiant tail-flick method in mice, and better flexibility in regaining their size. Being less of an irritant, these vesicular carriers were also found to be more comfortable on human skin. Thus, the capsaicin-loaded FMVs offer high potential as topical drug delivery technologies with improved patient acceptance and effectiveness.

Topical treatment in vitiligo and the potential uses of new drug delivery systems

Vitiligo is a psychologically devastating condition. Topical therapy is employed as first-line treatment in localized vitiligo. Currently, several topical agents are available in many forms viz. methoxsalen (solution and cream), trioxsalen (solution), corticosteroids (gel, cream, ointment and solution) and calcineurin inhibitors (ointment and cream). Although topical therapy has an important position in vitiligo treatment, side-effects or poor efficacy affect their utility and patient compliance. Novel drug delivery strategies can play a pivotal role in improving the topical delivery of various drugs by enhancing their epidermal localization with a concomitant reduction in their side-effects and improving their effectiveness. The current review emphasizes the potential of various phospholipid based carriers viz. liposomes, transferosomes, ethosomes, lipid emulsions, solid lipid nanoparticles and organogels in optimizing and enhancing the topical delivery of anti-vitiligo agents, whilst reducing the side effects of drugs commonly used in its topical treatment.

Phospholipid‐based formulation with improved attributes of coal tar

Purpose  The aim of this study was to evaluate the formulation characteristics and pharmacodynamic activity of the lecithinized coal tar formulation (LCT) employing different methodologies and compare it with that of a conventional coal tar formulation (CCT) employing different methodologies.

Novel phospholipid-based topical formulations of tamoxifen: evaluation for antipsoriatic activity using mouse-tail model

Abstract Objective: Tamoxifen (TAM) is widely employed in the treatment of breast malignancies and is also found to be effective in psoriasis treatment. The current studies aimed to explore the antipsoriatic potential of topical TAM encapsulated in the new generation phospholipid-based vesicular and micellar systems, i.e. flexible membrane vesicles (FMVs) and pluronic lecithinized organogels (PLOs). Methods: TAM-loaded-FMVs were prepared by thin-film hydration technique, while TAM–PLOs were prepared by simple mixing. Mouse-tail model was used to evaluate the antipsoriatic activity of the novel formulations. The mouse tails were treated once-a-day with different formulations for a period of four weeks and prepared for longitudinal histological sections by hematoxylin–eosin staining technique. The length of the orthokeratotic regions in stratum granulosum was measured on 10 sequential scales per tail section as percentage of the full length of the scale, and the drug activity was calculated further. Results: Evaluation of antipsoriatic activity on mice tail revealed significantly higher (p < 0.01) efficacy of TAM–FMV gel (i.e. 35.8%) and TAM–PLO (i.e. 24.6%) vis-à-vis the conventional TAM–hydrogel (i.e. 10.2%). Conclusions: The results of these studies demonstrated immense potential of the topically applied TAM-encapsulated vesicular and micellar systems in psoriasis, thus calling for more comprehensive investigations to establish the role of TAM in the management of psoriasis.

Tamoxifen-loaded novel liposomal formulations: evaluation of anticancer activity on DMBA-TPA induced mouse skin carcinogenesis

Purpose: Tamoxifen (TAM) is a non-steroidal estrogen receptor modulator known for its anticancer activity. Apart from marked breast cancer activity, this drug has also shown potential in treating other types of cancers including skin cancers. TAM is reported to be associated with serious side effects primarily due to its systemic distribution. The localized delivery of this drug in this regard would be highly beneficial with respect to safety as well as efficacy. Methods: In the current studies, an endeavor has been made to investigate the efficacy of topically applied liposome-encapsulated TAM on skin cancer model. The drug was encapsulated in phospholipid-based vesicular systems viz. conventional liposomes and elastic liposomes. Incidence of papillomas and histopathological examination were employed to determine the efficacy of the tested formulations. Results: The results demonstrated carrier-dependent strong inhibition of skin carcinogenesis with encapsulated drug vis-à-vis drug in the solution form. The encouraging findings from the current work construe immense potential of the TAM-loaded liposomal systems in the management of skin cancer.

Tamoxifen-encapsulated vesicular systems: cytotoxicity evaluation in human epidermal keratinocyte cell line

AIM Tamoxifen is a nonsteroidal estrogen receptor modulator indicated in the treatment of breast cancer. Apoptosis has been reported to be a major mechanism for its antitumor effect. Tamoxifen has also shown significant potential in treating various dermatological disorders including psoriasis, characterized by hyperproliferation of epidermal keratinocytes. An endeavor was made in the current studies to investigate the potency of vesicle-encapsulated tamoxifen on human epidermal keratinocyte cell lines. METHODS Drug was encapsulated in the phospholipid-based vesicular systems, namely, conventional liposomes and flexible-membrane liposomes. In vitro cytotoxicity evaluation of the formulations was carried out employing MTT cell proliferation assay. RESULTS A composition-dependent strong inhibition in the viability of epidermal keratinocyte cells was observed. CONCLUSION The encouraging findings of this work construe immense potential of the tamoxifen-encapsulated vesicular systems in the management of psoriasis.