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Review
. 2023 Jul 6;16(7):967.
doi: 10.3390/ph16070967.

Smart Strategies to Overcome Drug Delivery Challenges in the Musculoskeletal System

Brandon Vorrius  1 , Zhen Qiao  1 , Jonathan Ge  1 , Qian Chen  1
Affiliations
Review

Smart Strategies to Overcome Drug Delivery Challenges in the Musculoskeletal System

Brandon Vorrius et al. Pharmaceuticals (Basel). .

Abstract

The musculoskeletal system (MSKS) is composed of specialized connective tissues including bone, muscle, cartilage, tendon, ligament, and their subtypes. The primary function of the MSKS is to provide protection, structure, mobility, and mechanical properties to the body. In the process of fulfilling these functions, the MSKS is subject to wear and tear during aging and after injury and requires subsequent repair. MSKS diseases are a growing burden due to the increasing population age. The World Health Organization estimates that 1.71 billon people suffer from MSKS diseases worldwide. MSKS diseases usually involve various dysfunctions in bones, muscles, and joints, which often result in pain, disability, and a decrease in quality of life. The most common MSKS diseases are osteoporosis (loss of bone), osteoarthritis (loss of cartilage), and sarcopenia (loss of skeletal muscle). Because of the disease burden and the need for treatment, regenerative drug therapies for MSKS disorders are increasingly in demand. However, the difficulty of effective drug delivery in the MSKS has become a bottleneck for developing MSKS therapeutics. The abundance of extracellular matrix and its small pore size in the MSKS present a formidable barrier to drug delivery. Differences of vascularity among various MSKS tissues pose complications for drug delivery. Novel strategies are necessary to achieve successful drug delivery in different tissues composing the MSKS. Those considerations include the route of administration, mechanics of surrounding fluids, and biomolecular interactions, such as the size and charge of the particles and targeting motifs. This review focuses on recent advances in challenges to deliver drugs to each tissue of the MSKS, current strategies of drug delivery, and future ideas of how to overcome drug delivery challenges in the MSKS.

Keywords: bone; cartilage; drug delivery; muscle; musculoskeletal system; tissue barriers.

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Conflict of interest statement

Q.C. is a co-founder of NanoDe Therapeutics Inc.

Figures

Figure 1
Figure 1
Administration routes targeting avascular and vascular tissues in the MSKS. Local delivery such as intra-articular injection is often used to target avascular tissues including tendon and ligament (A) and cartilage (B). Systemic delivery such as intravenous (IV) injection is often used for drug delivery to vascular tissues such as bone (C) and muscle (D).
See this image and copyright information in PMC

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