D2.245 - Dithranol loaded Dendritic nanoarchitectures for the treatment of psoriasis

Psoriasis is a multigenic, cutaneous inflammatory disorder, involving a variety of pathological changes in skin. Psoriasis is characterized as chronic, recurring, genetically determined, immune-mediated inflammatory skin disease characterized by scaly patches due to excessive skin production. Skin rapidly accumulates at the site of onset and takes a white silvery appearance which erodes with excessive itching. The study aimed to evaluate the potential of dendrimers for safe and efficient topical delivery of antipsoriatic agent Dithranol, one of the most promising anti-psoriatic agents via topical route whose application is inconvenient and troublesome, to increase the therapeutic efficacy of Dithranol by increasing its retention time and to decrease the irritation, local burning sensation and temporary staining of skin caused by Dithranol.

The Polypropylene Imine dendrimers (PPID) were synthesized by divergent synthesis method. The ethylene diamine was used as core material and acrylonitrile to form branching units. Dendrimers were then characterized by IR & NMR spectroscopy and transmission electron microscopy. Dithranol loaded PPID were evaluated for in-vitro skin permeation and drug release, haemolytic toxicity, skin irritation studies, tape stripping studies and fluorescence microscopy.

Loading of Dithranol was found to be pH dependent with maximum encapsulation at acidic pH. PPID showed significantly enhanced permeation rate constant and lesser skin irritation when compared with the plain drug solution. Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. The entrapment of drug in dendritic system reduced skin irritation, haemolytic toxicity, enhanced permeation rate constant and penetration and accumulation in the skin. The Dithranol loaded dendrimers extended drug retention time in the skin vis-a-vis reducing the associated disadvantages and improving the topical bioavailability of the molecules in a controlled pattern. It has been shown to be effective in increasing the flux of drug across the rat skin. 

The enhanced accumulation of drug via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of Dithranol for the treatment of psoriasis.