Design and optimization of a novel herbosomal-loaded PEG-poloxamer topical formulation for the treatment of cold injuries: a quality-by-design approach.

The spectrum of cold injuries ranges from frostnip, chilblains to severe frostbite. Cold injuries occur upon prolonged exposure to freezing temperature and are pathologically a combination of ice crystal formation in the tissue resulting in inflammation, thrombosis and ischemia in the extremities, often necessitating limb amputation in extreme cases due to tissue necrosis. Severe forms of frostbite are a cause of major concern to patients as well as the treating physician. Due to the lack of effective treatment modalities and paucity of research on prophylaxis and therapeutics of cold injuries, we developed a novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) employing quality-by-design (QBD) approach. Natural compounds exhibiting potent therapeutic potential for the management of cold injuries were incorporated in novel lipid vesicles (herbosomes) loaded in PEG-poloxamer polymers. The herbosomal formulation effectively creates an occlusion barrier that promotes epithelial regeneration, desmosome scale-up and angiogenesis and thus promotes rapid healing, indicating controlled release of herbosomes. Optimized novel herbosomes showed entrapment efficiency > 90% and < 300 nm mean particle size and in vitro drug permeation of about 2 µg/cm2 followed Higuchi's release kinetics. Skin irritancy study on female Sprague-Dawley rats showed no edema or erythema. In vivo bio-efficacy study revealed significant efficacy (p < 0.05) when compared to the standard treatment groups. Graphical abstract presenting the designing and optimization of novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) and predictive model for the in vivo study of the developed n-HPTF on cold injury rat skin model.