Khomendra Kumar Sarwa

Topical ethosomal capsaicin attenuates edema and nociception in arthritic rats.

Abstract In this study, topical ethosomal formulation of capsaicin was prepared and evaluated for bio-efficacy in arthritic rats. Physical and biological characterizations of prepared capsaicin-loaded nano vesicular systems were also carried out. Ethosomal capsaicin showed significant reduction of rat paw edema along with promising antinociceptive action. The topical antiarthritic efficacy of prepared formulation of capsaicin was found more than that of Thermagel, a marketed gel of capsaicin. From toxicological study, no predictable signs of toxicity such as skin irritation (of experimental rats) were observed. Based on this finding, ethosomal capsaicin could be proposed as an effective as well as a safe topical delivery system for the long-term treatment of arthritis and associated inflammo-musculoskeletal disorders. Such exciting result would eventually enlighten the analgesic and anti-inflammatory potential of capsaicin for topical remedy.

Fluidity enhancement: a critical factor for performance of liposomal transdermal drug delivery system.

Abstract Liposomes are well known lipid carriers for drug delivery of bioactive molecules encapsulated inside their membrane. Liposomes as skin drug delivery systems were initially promoted primarily for localized effects with minimal systemic delivery. Subsequently, a novel vesicular system, transferosomes was reported for transdermal delivery with efficiency similar to subcutaneous injection. The multiple bilayered organizations of lipids applied in these vesicles structure are somewhat similar to complex nature of stratum corneal intercellular lipids domains. The incorporation of novel agents into these lipid vesicles results in the loss of entrapped markers but it is similar to fluidization of stratum corneum lipids on treatment with a penetration enhancer. This approach generated the utility of penetration enhancers/fluidizing agents in lipids vesicular systems for skin delivery. For the transdermal and topical applications of liposomes, fluidity of bilayer lipid membrane is rate limiting which governs the permeation. This article critically reviews the relevance of using different types of vesicles as a model for skin in permeation enhancement studies. This study has also been designed to encompass all enhancement measurements and analytical tools for characterization of permeability in liposomal vesicular system.

Tamoxifen Citrate Loaded Ethosomes for Transdermal Drug Delivery System: Preparation and Characterization

Long term tamoxifen citrate therapy is imperative to treat several dermatological and hormonal sensitive disorders. Successful oral and parenteral administration of tamoxifen citrate has been challenging since it undergoes enzymatic degradation and has poor aqueous solubility issues. In the present work, tamoxifen citrate loaded ethosomes were prepared and characterized for transdermal applications. The prepared formulations were characterized for morphological features, particle size distribution, calorimetric attributes, zeta potential and drug entrapment. Permeation profile of prepared ethosomes was compared with liposomes and hydroethonalic solution across cellophane membrane and human cadaver skin. Results of the permeation studies indicate that ethosomes were able to deliver >90% drug within 24 hours of application, while liposomes and hydroethanolic solution delivered only 39.04% and 36.55% respectively. Skin deposition and stability studies are also reported.

Potential of capsaicin-loaded transfersomes in arthritic rats

Abstract In the present study, the biopotential of capsaicin (an active principle of capsicum) as a topical antiarthritic agent was studied in arthritic rats. Transfersomal vesicular system was employed for the topical administration of capsaicin in experimental rats. The characterization of prepared capsaicin-loaded transfersomes reveals their nano size (94 nm) with negative surface charge (−14.5 mV) and sufficient structural flexibility, which resulted in 60.34% entrapment efficacy, penetration across the biomembrane (220 µm) and 76.76% of drug release from vesicular system in 24 h in their intact form as evident from confocal laser scanning micrographic study. Results of transfersomal nanoformulation (capsaicin loaded, test) were compared with that of conventional gel formulation available in the market (Thermagel, standard), with an aim to assess the antiarthritic efficacy of our prepared capsaicin-loaded transfersomal formulation. In vivo antiarthritic activity study shows that our formulation possesses superior inhibitory activity than the marketed Thermagel formulation at the same dosage level, which could probably be due to the lesser permeability of Thermagel across the dermal barriers compared to our specially designed transfersomal delivery system. Moreover, the better tolerance of prepared vesicular formulation in biological system further enlightens the suitability of the transfersomal vesicle to be used as a novel carrier system for the topical administration of such highly irritant substance.

Penetration of Tamoxifen Citrate Loaded Ethosomes and Liposomes Across Human Skin: A Comparative Study with Confocal Laser Scanning Microscopy

In the present study, ethosomal and liposomal formulations containing tamoxifen citrate were prepared and evaluated for their penetration properties in human cadaver skin using Franz diffusion cell and confocal laser scanning microscope (CLSM). The results clearly revealed that ethosomal vesicles showed a better drug permeation profile than that of liposomal vesicles. In addition, low fluorescence intensity in CLSM was recorded with liposomes as compared to ethosomes, indicating lower cumulative amount of drug permeation from liposomal vesicles. Furthermore, CLSM showed uniform fluorescence intensity across the entire depth of skin in ethosomal treatment, indicating high penetrability of ethosomal vesicles through human cadaver skin. In contrast, low penetrability of conventional liposomal vesicles was recorded as penetration was limited to the 7(th) section (i.e. upper epidermis layer) of skin as evident from visualization of intact liposomal vesicles in CLSM.

A nanovesicle topical formulation of Bhut Jolokia (hottest capsicum): a potential anti-arthritic medicine

Objectives: Bhut Jolokia is a capsicum variety indigenous to Northeast India and is recognized as the hottest capsicum variety of the world. The ethnobotanical survey revealed that it has potential anti-arthritic activity but its topical adverse events restrict its usability. In the present study, the semipurified capsaicinoids extract of Bhut Jolokia was formulated as a topical formulation via ethosomal nanovesicle approach, which enhanced the acceptability. Methods: Prepared formulation was optimized by surface response methodology and characterized for morphology, zeta potential, differential scanning calorimetry study and permeation and penetration studies. The experimental formulations were characterized on Freunds complete adjuvant-induced chronic arthritis model. Results: Ethosomal nanovesicles prepared with the semipurified capsaicinoids extract demonstrated good anti-arthritic activity in rat model, superior to Thermagel (a marketed formulation of capsaicin) in the reduction of joint swelling and pain throughout the observation period. Nanovesicle formulation showed better tolerability and acceptance on both animal and human models. Results obtained from the study strengthen the potential application of Bhut Jolokia semipurified extract in an ethosomal nanovesicle carrier as a topical analgesic as well as an anti-arthritic. Conclusion: The significant positive results, with reduced irritant effect of the semipurified capsaicinoids extract of Bhut Jolokia-loaded ethosomal nanovesicle carrier, suggest that it could be one of the choices for formulation development in anti-arthritic medicine.

Phytochemical and biological potential of Cassia tora Linn.

Cassia tora Linn. (Caesalpinaceae) is a semi-wild annual herb grown widely in different places of south-east Asia including India, Northern Australia and Americas. This plant species is well known for having potential in traditional medicine practices for the treatment of a variety of disorders and ailments ranging from simple cough, hypertension to diabetes. Recent scientific investigation reveals its phytochemical as well as biological potential. C. tora has been proven to be medicinally effective for having antimicrobial, antiantioxidant, antihypertensive, antidiabetic and antimutagenic activities, just to name a few. This paper encompasses a comprehensive review on phytochemical and biological aspects of Cassia tora L.

Topical Analgesic Nanolipid Vesicles Formulation of Capsaicinoids Extract of Bhut Jolokia (Capsicum chinense Jacq): Pharmacodynamic Evaluation in Rat Models and Acceptability studies in Human Volunteers.

Capsicum fruit is used for treating skeletomuscular disorders as a counterirritant analgesic around the globe. But its concentration-dependent irritation and concomitant withdrawal of therapy by the patients hampers its therapeutic usefulness. In the present study, a novel nanolipid approach based on elastic phospholipid vesicles was employed to encapsulate a semipurified extract of Bhut Jolokia for topical drug delivery application. The working hypothesis was that encapsulation of irritant extract into nanolipid vesicles may prevent the initial rejection of formulation and the elastic vesicles may facilitate deeper skin penetration over a shorter time period. Surface response methodology was adopted to study the effect of selected independent formulation variables on dependent variables like vesicle size and entrapment efficacy. The prepared formulations were characterized for various physicochemical parameters. The efficacy of the newly developed nonolipid vesicle formulation loaded with semipurified extract of Bhut Jolokia was tested on carrageenan and formaldehyde-induced inflammation as well as Freunds adjuvant-induced arthritis model. The novel formulations were tested on human volunteers in a Phase I clinical trial and were found to be acceptable. The study indicates that this strategy holds immense potential for topical delivery of the bioactive from Bhut Jolokia and can pave the way for its clinical applications.