Design and Optimization of a Novel-Herbosomal Loaded PEG-Poloxamer Topical Formulation For the Treatment of Cold Injuries: A Quality By Design Approach

Abstract

Cold injury/injuries can range from minor chilblain to extreme form of frostbite. Cold injuries are pathologically a combination of ice crystal formation in tissue with inflammation, thrombosis and ischemia to extremities, necessitating limb amputation in extreme cases due to tissue necrosis. Less severe forms of cold injuries can be managed by gentle rewarming of limb and avoiding exposure to cold leading to favorable outcomes, however severe forms of frostbite are a cause of major concern to patients as well as the treating physician. Due to lack of effective pre-treatment modalities and paucity of research in prophylaxis and therapeutics of cold injuries, we have developed a novel-herbosomal loaded PEG-Poloxamer topical formulation (n-HPTF) by Quality by Designed approach, incorporating natural ingredients which are having potential therapeutic effect for the treatment of cold injury in a form of a novel-lipid vesicles (herbosomes) loaded in polymers (PEG-3350 and Poloxamer-188) resulting excellent occlusive barrier and thus promote rapid healing. Optimized novel-herbosomes showed entrapment efficiency > 90% and < 300 nm mean particle size and in-vitro drug permeation of about 2 µg/cm2 followed by Higuchi’s release kinetic. Skin irritancy study on female Sprague Dawley rats showed no edema or erythema. In-vivo bio-efficacy study was performed and found significantly good at p-value < 0.05 when compared to the standard treatment groups.