PMID- 32217157 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20220331 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 581 DP - 2020 May 15 TI - A comparative pilot study of oral diacerein and locally treated diacerein-loaded nanoparticles in a model of osteoarthritis. PG - 119249 LID - S0378-5173(20)30233-7 [pii] LID - 10.1016/j.ijpharm.2020.119249 [doi] AB - Diacerein (DIA) is a slow-acting drug for osteoarthritis (OA). Oral DIA administration, however, exerts side effects including diarrhea and urine discoloration. We fabricated DIA-loaded poly(d,l-lactide-co-glycolide) nanoparticles (DIA/PLGA NPs) that allow sustained release of DIA. In vitro, rat synoviocytes were used to investigate the cytotoxicity and anti-inflammatory effects of DIA-loaded NPs. In vivo, monosodium iodoacetate (MIA)-induced OA rats were divided into seven groups that included non-treated healthy control rats and rats injected with MIA alone or in combination with NPs, DIA(5%) solution, DIA(1%)/NPs, DIA(5%)/NPs, or oral DIA. The in vitro studies revealed that DIA/PLGA NPs dose-dependently suppressed mRNA levels of pro-inflammatory cytokines and enzymes, including interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha, matrix metalloproteinase-3 (MMP-3), MMP-13, cyclo-oxygenase-2, and a disintegrin and metalloproteinase with thrombospondin motifs-5 in synoviocytes. The in vivo studies demonstrated that intra-articular treatment of OA rat models with DIA-loaded PLGA NPs markedly decreased mRNA levels of these pro-inflammatory factors and increased those of anti-inflammatory cytokines (IL-4 and IL-10). Micro-computed tomography and histological evaluations indicated that intra-articular injection of DIA-loaded NPs was effective in protecting against cartilage degradation. Administration of DIA/PLGA NPs via intra-articular injection is promising for inhibiting inflammation and protecting against cartilage degradation in OA. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Jung, Jae Hyun AU - Jung JH AD - Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, Republic of Korea. Electronic address: mcfriend82@naver.com. FAU - Kim, Sung Eun AU - Kim SE AD - Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea. Electronic address: sekim10@korea.ac.kr. FAU - Kim, Hak-Jun AU - Kim HJ AD - Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea. Electronic address: hjunkimos@gmail.com. FAU - Park, Kyeongsoon AU - Park K AD - Department of Systems Biotechnology, Chung-Ang University, 4726 Seodong-daero, Daedeok-myeon, Anseong-si, Gyeonggi-do 17546, Republic of Korea. Electronic address: kspark1223@cau.ac.kr. FAU - Song, Gwan Gyu AU - Song GG AD - Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Republic of Korea. Electronic address: gsong@kumc.or.kr. FAU - Choi, Sung Jae AU - Choi SJ AD - Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, Republic of Korea. Electronic address: csjmd888@korea.ac.kr. LA - eng PT - Comparative Study PT - Journal Article DEP - 20200323 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 0 (Anthraquinones) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Drug Carriers) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 4HU6J11EL5 (diacerein) RN - WF5188V710 (Iodoacetic Acid) SB - IM MH - Administration, Oral MH - Animals MH - Anthraquinones/*administration & dosage/adverse effects/pharmacokinetics MH - Anti-Inflammatory Agents/*administration & dosage/adverse effects/pharmacokinetics MH - Arthritis, Experimental/chemically induced/diagnosis/*drug therapy/pathology MH - Cartilage, Articular/diagnostic imaging/drug effects/pathology MH - Diarrhea/chemically induced/prevention & control MH - Dose-Response Relationship, Drug MH - Drug Carriers/*chemistry MH - Drug Liberation MH - Humans MH - Injections, Intra-Articular MH - Iodoacetic Acid/toxicity MH - Male MH - Nanoparticles/chemistry MH - Osteoarthritis/chemically induced/diagnosis/*drug therapy/pathology MH - Pilot Projects MH - Polylactic Acid-Polyglycolic Acid Copolymer/chemistry MH - Primary Cell Culture MH - Rats MH - Synoviocytes MH - X-Ray Microtomography OTO - NOTNLM OT - Anti-inflammation OT - Diacerein OT - Intra-articular injection OT - Poly(D,L-lactide-co-glycolide) OT - Sustained drug delivery COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/03/29 06:00 MHDA- 2021/02/02 06:00 CRDT- 2020/03/29 06:00 PHST- 2019/09/05 00:00 [received] PHST- 2020/02/19 00:00 [revised] PHST- 2020/03/20 00:00 [accepted] PHST- 2020/03/29 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] PHST- 2020/03/29 06:00 [entrez] AID - S0378-5173(20)30233-7 [pii] AID - 10.1016/j.ijpharm.2020.119249 [doi] PST - ppublish SO - Int J Pharm. 2020 May 15;581:119249. doi: 10.1016/j.ijpharm.2020.119249. Epub 2020 Mar 23.