title: Development and optimization of self-assembling nanosystem for intra-articular delivery of indomethacin.
abstract: Osteoarthritis is a propagated debilitating condition affecting patients' quality of life. Intra-articular injection approach was investigated as a localized treatment strategy providing: site-specific delivery, decreased side effects and, increased patient compliance. A 32full factorial experimental design was employed to prepare the indomethacin-loaded self-assembling nanosystems (SANS). The surfactant (Poloxamer 407/Tetronic 90R4) ratio and the poly(lactic-co-glycolic acid) (PLGA) concentration significantly affected encapsulation efficiency and drug release (p<0.05). The optimized formula was subjected to modification by addition of different proteoglycans, as a compensatory treatment, to improve its pharmacological properties. The modified SANS, containing glucosamine (150mg), was selected for in-vivo studies as it had a sustained drug release profile and a small particle size (173.90nm). The effect of the optimized SANS, with or without PLGA, was compared with the modified formula containing glucosamine and, with the drug suspension on the arthritic knee joints of rats. It was found that the formulation containing PLGA and glucosamine showed significantly higher reduction in both, knee diameter and TNF-α levels, compared to other groups. Furthermore, all SANS showed histological improvement in the cellularity of the synovial membranes and joints. Our results indicate that SANS containing PLGA and glucosamine is capable of treating arthritic joints.
authors.affiliation: Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Rabab
authors.initials: R
authors.lastname: Kamel
authors.affiliation: Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt.
authors.forename: Alaa H
authors.initials: AH
authors.lastname: Salama
authors.affiliation: Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo, Egypt. Electronic address: azza.ahmed@fue.edu.eg.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Mahmoud
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D007213:Indomethacin / Q000008:administration & dosage* / Q000737:chemistry*; D007270:Injections, Intra-Articular; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry*; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007213:Indomethacin
keywords: Indomethacin; Intra-articular; Micelles; Osteoarthritis; PLGA; Self-assembly