Development and Evaluation of Polymeric Nanoparticles Based Transdermal Hydrogel for Aceclofenac Delivery against Rheumatoid Arthritis

Abstract

Polycaprolactone owing to its biodegradable and biocompatible nature and its slow release kinetics is considered to be an excellent carrier for the drug delivery as well as in tissue engineering applications. The current study is based on the use of PCL for the transdermal delivery of aceclofenac for the effective management of Rheumatoid Arthritis. The transdermal route avoid the side effects produced if aceclofenac is given for long period of time through oral route and also bypass the first pass effect. Nanoprecipitation technique was employed to prepare PCL-NPs. And further they were optimized using design expert software. The software gave a positive correlation between studied parameters i.e. amount of polymer, surfactant and drug and the responses generated (entrapment efficiency and Particle size). Organic to aqueous phase ratio, injection rate and stirring speed were kept constant. The optimized formulation had a particle size approx. 140 nm and entrapment efficiency 87%. Then characterization based on measurement of particle size and entrapment efficiency proved our formulation to be in nanosize range. There was no interaction among the components as seen through FTIR analysis and conversion of drug from crystalline to amorphous form in the nanoformulation indicated complete loading of drug in nanocarrier. The final formulation a carbopol based hydrogel loaded with ACE-NPs was also subjected to characterization and gave excellent spreadability, non Newtonian behavior for easy application and a pH compatible to the skin. The in vitro release studies gave a sustained release behavior of drug from NPs which was further sustained by loading in hydrogel and a signification permeation as accessed by ex vivo permeation study was seen across the skin through NPs based hydrogel and addition of Argan oil as permeation enhancer further enhanced the penetration owing to presence of oleic acid that causes fluidization of skin lipid matrix. Finally in vivo animal model was developed by inducing Complete Freund’s Adjuvant (CFA) in the mice paw and the behavioral parameters studied were mechanical allodynia, paw edema, arthritis index and thermal hyperalgesia and after the activity Histopathological and radiological evaluation of mice paw concluded that ACE-NPs based hydrogel effectively reduced the erythema and edema and improved the Histopathological and radiological features.