Development, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Poly-(ε-caprolactone) Microcapsules Prepared by Ultrasonic Atomization for Intra-Articular Administration

Abstract

Intra-articular administration of drugs to the joint in the treatment of joint disease has the potential to minimize the systemic bioavailability and the usual side-effects associated with oral drug administration. In this work, a drug delivery system is proposed to achieve an anti-inflammatory local effect using resveratrol (RSV). This study aims to develop microcapsules made of poly-(ε-caprolactone) (PCL) by ultrasonic atomization to preserve the antioxidant activity of RSV, to prevent its degradation and to suppress the inflammatory response in activated RAW 264.7 macrophages. An experimental design was performed to build a mathematical model that could estimate the effect of nozzle power and polymer concentration on particle size and encapsulation efficiency. RSV-loaded microcapsules showed adequate morphology, particle size, and loading efficiency properties. RSV formulations exhibited negligible cytotoxicity and an efficient amelioration of inflammatory responses, in terms of Nitric Oxide (NO), ROS (Reactive Oxygen Species), and lipid peroxidation in macrophages. Thus, RSV-loaded microcapsules merit consideration as a drug delivery system suitable for intra-articular administration in inflammatory disorders affecting the joint.

Tuning Microcapsule Shell Thickness and Structure with Silk Fibroin and Nanoparticles for Sustained Release

“…The yields of Cur-loaded NS710 and NS720 were 90.8 and 82.4%, respectively (Table 1), both of which were higher than that of Cur-loaded alginate/chitosan/gum arabic microcapsules (57.3%) 13 and comparable with that of Cur-loaded poly(ε-caprolactone) microcapsules (80.22−92.07%). 27 The Cur-microcapsules after methanol extraction became empty, but the shell remained intact (Figure 6c,f). The encapsulation efficiency (EE) of Cur-NS710 and Cur-NS720 microcapsules was 90.52 ± 2.58 and 95.26 ± 3.16%, while the drug loading (DL) was 8.46 ± 0.26 and 5.02 ± 50.17%, respectively (Figure S7), higher or comparable to those reported in SF microspheres (EE = 40.5 ± 3.6%; DL = 8.9 ± 0.8%).…”

3D Printed Tacrolimus Rectal Formulations Ameliorate Colitis in an Experimental Animal Model of Inflammatory Bowel Disease

“…This therapeutic effect was comparable to that obtained with the administration of an intraperitoneal corticosteroid or resveratrol in the form of an enema. The fact that treatment with tacrolimus has obtained a therapeutic effect similar to that of resveratrol can be explained by the antioxidant effect of the latter [42], since it is known that oxidative stress plays a role in the pathogenesis of IBD [43].…”

Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection

“…Intra-articular (IA) injection of corticosteroids, such as triamcinolone acetonide (TA) crystalline suspension, is commonly recommended to alleviate pain and inflammation in knee joints [1,2]. Marketed injectable TA suspensions are intended to be slowly dissolved in the synovial fluid, and the glucocorticoid molecules steadily bind to and activate the glucocorticoid receptors, obstructing the production of inflammation mediators, including prostaglandins, leukotrienes, and pro-inflammatory cytokines [3].…”

“…Several pharmaceutical approaches, including hydrogels, liposomes, nanoparticles, and microparticles (MPs), have been explored to prolong the retention time of steroidal compounds in the synovial tissues, minimizing systemic exposure following IA injection [2,10,11,12,13,14,15]. When considering the leaky structure of the synovium, one of the sound strategies for localized delivery to the synovial tissues is administering the therapeutic agents to IA after entrapping in a micro-sized carrier system.…”

“…When considering the leaky structure of the synovium, one of the sound strategies for localized delivery to the synovial tissues is administering the therapeutic agents to IA after entrapping in a micro-sized carrier system. Biocompatible and biodegradable polymeric MPs generally larger than 10 μm have been reported to be effective for remaining in the synovial cavity and providing a sustained-release profile in the joint [2,9,16]. Actually, a single IA injection of the PLGA MPs was clinically demonstrated to be effective in providing an extended retention time of the corticosteroid in joints while reducing the drug distribution in the bloodstream [17].…”