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Published on: August 10, 2020
Advancing drug delivery to articular cartilage: From single to multiple strategies
Tianyuan Zhao1,2, Xu Li3, Hao Li1,2
1Institute 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.
Abstract:
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.
Insights
Multiple drug delivery systems offer improved strategies for treating articular cartilage (AC) injuries and osteoarthritis (OA). Sequential and synergistic approaches are crucial for effective cartilage regeneration, overcoming limitations of single-agent therapies.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Drug Delivery Systems
Background:
- Articular cartilage (AC) injuries can lead to osteoarthritis (OA) due to poor self-repair capabilities.
- Current intra-articular drug delivery systems aim to enhance therapeutic localization and controlled release.
- Single-agent delivery systems struggle to address the multifactorial nature of cartilage pathology and heterogeneous structure.
Purpose of the Study:
- To review single-drug delivery strategies for articular cartilage diseases.
- To highlight advances in multiple drug delivery applications for cartilage regeneration.
- To inspire the rational design of future intra-articular drug delivery systems (DDSs).
Main Methods:
- Comprehensive literature review of single-drug delivery systems for AC diseases.
- Analysis of emerging multiple drug delivery strategies, including sequential and synergistic approaches.
- Examination of spatial distribution and heterogeneous regeneration aspects in drug delivery.
Main Results:
- Single-agent delivery systems have limitations in achieving comprehensive cartilage regeneration.
- Multiple drug delivery systems demonstrate potential through sequential targeting of pathological processes.
- Synergistic targeting and spatial distribution are key considerations for advanced DDSs.
Conclusions:
- Sequential drug delivery strategies are essential for addressing the complexity of cartilage injury.
- Multiple drug delivery systems offer a promising avenue for mimicking natural biosynthesis and achieving full cartilage regeneration.
- Future research should focus on designing sophisticated DDSs for effective AC disease treatment.
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