Intra-articular multifunctional celecoxib loaded hyaluronan nanocapsules for the suppression of inflammation in an osteoarthritic rat model

Abstract

Direct intra-articular delivery of drugs to osteoarthritic joints offers the possibility of delivering high drug concentrations at the site of action as well as decreasing long term associated side effects after oral drug delivery. So in the current work, we aimed to improve the osteoarthritic therapeutic efficacy of the non-steroidal anti-inflammatory drug; celecoxib, through the formulation of drug loaded hyaluronan nanocapsules. The proposed formulation aimed to combine the beneficial viscosupplemental properties of hyaluronic acid with the pharmacological, anti-inflammatory, effect of celecoxib in a novel drug carrier for intra-articular delivery. The proposed nanocapsules were prepared by the nanoprecipitation method. Several formulation variables were studied aiming at optimizing the nanocapsules' size, polydispersity index and celecoxib entrapment efficiency %. The optimized hyaluronan nanocapsules formulation showed a size of 254.9 ± 3.06 nm, which is appropriate for the intra-articular delivery of celecoxib, high entrapment efficiency% of 97.98% ± 0.19, and prolonged celecoxib release for almost one week. The transmission electron microscope images revealed spherical shape of the nanocapsules with distinct shell and core structure. The in-vivo evaluation of the anti-osteoarthritic activity of the optimized hyaluronan nanocapsules formulation showed the superiority of the prepared celecoxib nanocapsules compared to celecoxib suspension in a Monoiodoacetate induced osteoarthritic rat model, regarding histological, swelling and immunohistochemical parameters of osteoarthritis.