Mechanistic insights into high permeation vesicle-mediated synergistic enhancement of transdermal drug permeation.

Aim: To design a nanocarrier platform for enhanced transdermal drug permeation. Materials & methods: Gel-based high permeation vesicles (HPVs) were developed and their performance in terms of transdermal flux improvement, in vitro release and skin irritancy was assessed. The mechanistic insights of permeation enhancement were explored using confocal laser scanning microscopy, ATR-FTIR, DSC and P31 NMR. Results: HPVs exhibited as vesicles with uniform size (∼150 nm), extended drug-release profile (∼48 h) and improved transdermal flux. HPVs were also nontoxic and nonirritant to skin. Enhanced vesicle deformability, improved vesicle membrane fluidity and synergistic permeation enhancement action of synergistic combination of permeation enhancer components was found to be responsible for HPV-mediated permeation enhancement. Conclusion: Overall, the study established that HPVs demonstrate a promising therapeutic advantage over conventional transdermal drug carriers.

Skin delivery of resveratrol encapsulated lipidic formulation for melanoma chemoprevention.

Objective: An unmet need for patient friendly products can be achieved with novel, biocompatible lipidic formulations which encapsulate and prolong release of medicaments. The aim of this study was to develop a commercially scalable resveratrol-loaded solid-lipid microparticulate (SLM) topical gel for melanoma chemoprevention. Methods: Preformulation studies were conducted and drug-excipient interactions examined using infra-red spectroscopy and differential scanning calorimetry (DSC). Resveratrol-loaded SLM topical gel was prepared and evaluated by in vitro and in vivo parameters. Results: Spherical microparticles of 2.98 µm average size were obtained and DSC thermograms provide evidence of trans-resveratrol encapsulation. In vitro and ex vivo drug diffusion studies revealed sustained release profiles. Optimised SLM gel provides optimum antioxidant, tyrosinase inhibition, cytotoxicity in B16F10 melanoma cell line and apoptosis efficacy. In vivo studies on C57BL mice exhibit significant tumour reduction. Conclusion: Promising role of trans-resveratrol-loaded SLM topical gel in melanoma chemoprevention is proven.

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis.

AIM: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis. METHODS: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments. RESULTS: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment. CONCLUSIONS: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.