Development and characterization of oxaceprol‐loaded poly‐lactide‐co‐glycolide nanoparticles for the treatment of osteoarthritis

Abstract

Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by doubleemulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration. K E Y W O R D Sintra-articular injection, nanoparticle, osteoarthritis, oxaceprol, PLGA

Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

“… [ 141 ] PNPs PLGA Oxaceprol Slow release In vitro - The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. [ 149 ] PLGA Diacerein Slow release In vitro & vivo Synoviocytes; Rats The in vitro studies revealed that DIA/PLGA NPs dose-dependently suppressed mRNA levels of pro-inflammatory cytokines and enzymes; In vivo studies have showed that intra-articular injection of DIA-PLGA nanoparticles could significantly reduce the mRNA level of the above pro-inflammatory factors, increase the mRNA level of anti-inflammatory cytokines (IL-4 and IL-10), and effectively prevent cartilage degeneration. [ 150 ] PLA KGN Improve drug bioavailability; Slow release In vitro & vivo Synoviocytes; Mice Polymer microparticles showed an extended drug release of 62% over 3 months; In vitro, these particles did not change the mitochondrial activity of cultured human osteoarthritis synovial cells.…”

“…Several studies report significantly improved and sustained drug release using PNPs for drug delivery. PLGA, 149 , 150 polylactic acid (PLA), 151 polyurethane, 152 different polymer combinations, 153 silk fibroin, 154 and polymer-grafted mesoporous silica 155 used to prepare PNPs for drug delivery. These formulations reportedly provide improved and sustained drug-release profiles for celecoxib, curcumin, and KGN by IA drug delivery.…”

Polymer particles for the intra-articular delivery of drugs to treat osteoarthritis

“…Alarçin et al prepared PLGA particles loaded with the anti-inflammatory drug oxaceprol (OXC) [82]. OXC is N-acetyl-L-hydroxyproline, which inhibits the inflammatory cascade by preventing granulocyte and leukocyte infiltration into joints and decreases the adherence of leukocytes to the blood vessel endothelium [158,159].…”

Rapamycin-loaded Poly(lactic-co-glycolic) acid nanoparticles: Preparation, characterization, and in vitro toxicity study for potential intra-articular injection

“…It has been extensively studied for the development of devices for the controlled delivery of macromolecules. PLGA particles loading Rapamycin were already described (Alarcin et al, 2020;Butoescu et al, 2009;Gerwin et al, 2006;Haeri et al, 2018;Jung et al, 2020;Kapoor et al, 2015;Riffault et al, 2015;Zerrillo et al, 2019;Zhang and Huang, 2012). For example, Dhanabalan et al (Dhanabalan et al, 2020) described Rapamycin microparticles' cytocompatibility on the human chondrocyte cell line (C28/I2, used as a model cell line for studying normal and pathological cartilage repair mechanisms related to chondrocyte biology and physiology).…”