PMID- 37799383 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231026 IS - 2211-3835 (Print) IS - 2211-3843 (Electronic) IS - 2211-3835 (Linking) VI - 13 IP - 10 DP - 2023 Oct TI - Advancing drug delivery to articular cartilage: From single to multiple strategies. PG - 4127-4148 LID - 10.1016/j.apsb.2022.11.021 [doi] AB - Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future. CI - (c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. FAU - Zhao, Tianyuan AU - Zhao T AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Li, Xu AU - Li X AD - Musculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, 999077, Hong Kong, China. FAU - Li, Hao AU - Li H AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Deng, Haoyuan AU - Deng H AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Li, Jianwei AU - Li J AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Yang, Zhen AU - Yang Z AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. AD - Arthritis Clinic & Research Center, Peking University People's Hospital, Peking University, Beijing 100044, China. FAU - He, Songlin AU - He S AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Jiang, Shuangpeng AU - Jiang S AD - Department of Joint Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. FAU - Sui, Xiang AU - Sui X AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. FAU - Guo, Quanyi AU - Guo Q AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. FAU - Liu, Shuyun AU - Liu S AD - Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing 100853, China. AD - School of Medicine, Nankai University, Tianjin 300071, China. LA - eng PT - Journal Article PT - Review DEP - 20221125 PL - Netherlands TA - Acta Pharm Sin B JT - Acta pharmaceutica Sinica. B JID - 101600560 PMC - PMC10547919 OTO - NOTNLM OT - Articular cartilage OT - Biomaterials OT - Cartilage injury OT - Cartilage regeneration OT - Drug delivery systems OT - Multiple drug delivery strategy OT - Osteoarthritis OT - Therapeutic factors EDAT- 2023/10/06 06:43 MHDA- 2023/10/06 06:44 PMCR- 2022/11/25 CRDT- 2023/10/06 03:48 PHST- 2022/08/02 00:00 [received] PHST- 2022/10/09 00:00 [revised] PHST- 2022/10/28 00:00 [accepted] PHST- 2023/10/06 06:44 [medline] PHST- 2023/10/06 06:43 [pubmed] PHST- 2023/10/06 03:48 [entrez] PHST- 2022/11/25 00:00 [pmc-release] AID - S2211-3835(22)00488-9 [pii] AID - 10.1016/j.apsb.2022.11.021 [doi] PST - ppublish SO - Acta Pharm Sin B. 2023 Oct;13(10):4127-4148. doi: 10.1016/j.apsb.2022.11.021. Epub 2022 Nov 25.