Quality by Design Enabled Systematic Optimization of Calcineurin Inhibitor-loaded Polymeric Nanoparticles for Sustained Topical Delivery in Psoriasis

Abstract

The present work describes the systematic development and optimization of cyclosporine-A loaded biodegradable polymeric nanoparticulate system using quality by design paradigm, to achieve an effective and sustained release of the cyclosporine-A to the targeted lesion of plaque psoriasis. The polymeric nanoparticles were formulated using the solvent emulsification method using Polycaprolactone and Hyaluronic acid as polymers. An Ishikawa fishbone diagram was constructed for risk assessment and to describe various plausible product and process variables influencing the quality target product profile. Critical process and product parameters were further optimized by Response surface methodology using Central Composite Design by Minitab 19 Software. The development and optimization of cyclosporine-A loaded biodegradable polymeric nanoparticles were further carried out by developing the relationship of independent variables viz. amount of polymers polycaprolactone and hyaluronic acid on dependent variables viz. particle size, zeta potential, and entrapment efficiency and exploring their interactions. Validation of the model was done by checkpoint analysis method. The particle size, zeta potential, and Entrapment efficiency of the optimized polymeric nanoparticles were found to be 317.2 ± 1.271, -0.249 ± 0.903 mV and 83.33 ± 1.124%, respectively. SEM images of the lyophilized nanoparticles showed spherical particles. In-vitro drug release study showed a slow and sustained release of 88.52 ± 1.10% of drugs up to 14 days. The nanoparticulate system would also help in overcoming the problem associated with poor water solubility and low permeability of the drug and will explore drug loaded biodegradable polymeric nanoparticles as a novel platform for effective therapy of psoriasis.