Nanoparticles Loaded Gels for Topical Delivery of Curcumin and Celecoxib for the Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is known as the third leading cause of physical disability due to its high prevalence, specifically among the elderly population. Curcumin is a drug of natural origin which has marked anti-inflammatory activity while Celecoxib is one of the drugs prescribed as first line treatment for osteoarthritis. Both of these drugs have a reported synergistic anti-inflammatory activity. Therefore, it was considered important to combine these two drugs in a single nano formulation to further improve their efficiency and to minimize their associated toxicities. For this purpose, study was designed to prepare and characterize Curcumin – Celecoxib loaded Poly lactic co glycolic acid (PLGA) nanoparticles by oil in water (O/W) emulsion solvent evaporation technique. The prepared nanoparticles were then loaded into Carbopol-934 (CP-934) gel for topical application in OA. The nanoparticles were characterized for their size, size distribution, morphology, encapsulation efficiency and invitro release profile. Nanoparticles in the size range of 150 to 220 nm were successfully fabricated. A distinct spherical shape of nanoparticles was revealed in scanning electron microscopy (SEM). The drug release profile indicated approximately 80% release of both drugs from nanoparticles within 48 hours via Fickian diffusion mechanism. The CP-934 gels loaded with nanoparticles were also characterized for their spreadability, viscosity, stability and permeability studies. All the in-vitro characterizations demonstrated that the co-delivery of Curcumin and Celecoxib in PLGA nanoparticles loaded in CP-934 gel serve as an efficient carrier system for targeted delivery in Osteoarthritis. The drug content of both drugs in final gel formulation was approximately between 70% to 85% for both drugs. In addition, preliminary in-vivo studies were conducted on albino mice for therapeutic effectiveness of the prepared nano formulation.In this connection behavioral tests were conducted and statistically significant results with pvalue <0.05 were obtained in the group of animals treated with PLGA nanoparticle loaded gels of Curcumin and Celecoxib. Furthermore, detailed in-vivo studies will be essential to completely understand the synergistic mechanism of these two drugs in relevant animal models