Advanced nanoparticles for osteoarthritis: a review

Abstract

Osteoarthritis (OA) is the most common chronic joint disease, characterized by whole-joint degenerative disease with cartilage degeneration as the primary pathogenesis. It is also a major cause of disability and increased social costs, particularly among the elderly. With the aging population and increasing obesity rates, the incidence of OA increases annually. The main symptoms include joint pain and loss of joint function, which severely impact the quality of life and daily activities of patients. Despite numerous treatments attempted over the past few decades, the long-term treatments have been disappointing. The main challenge lies in the very low bioavailability of drugs within the joint cavity, Therefore, the development of a therapeutic approach with cartilage targeting and efficient bioavailability is the key point to address OA. This paper summarizes the latest research on the use of PLGA in drug delivery for the treatment of OA, which provides an important foundation and a more comprehensive perspective for the subsequent drug treatment of joint diseases. We hope this will lead to more accurate and effective treatment plans for arthritis patients and promote the continuous advancement of the medical field.

Keywords: OA; PLGA; cartilage; drug; nanoparticle.

Figure 1

(A) Deformation of OA in the distal and proximal interphalangeal joints, plain radiograph of an osteoarthritic hip joint and MRI of an osteoarthritic knee. Reproduced from Bijlsma et al. (117). (B) Schematic representation of healthy knee joint structure and pathological changes of knee OA. Reproduced from Mao et al. (13). (C) Changes and interactions of different tissue structures in OA disease. Reproduced from Bijlsma et al. (117). (D) Signaling pathways and structural changes in the development of OA. Reproduced from Glyn-Jones et al. (89). (E) The cause of pain in OA within a biopsychosocial model. Reproduced from Hunter et al. (10).

Figure 2

(A) The illustration on preparation and application of PLGA particle. (B) Preparation and characterization of flavopiridol-loaded PLGA particles. (C) Biodistribution of Flavopiridol-loaded microparticles (FPs) following intra-articular injection in rats. (D) NF-κB activity of FPs. (E) Release kinetic of FPs. Reproduced from Sangsuwan et al. (50).

Figure 3

(A) The mechanism of melatonin-loaded nano-delivery system (MT@PLGA-COLBP) with cartilage-targeting effect for OA therapy. (B) Synthesis and characterization of MT@PLGA-COLBP NPs. (C) MT@PLGA-COLBP NPs target chondrocytes. (D) MT@PLGA-COLBP improves the protein expression of immune response and cartilage matrix in vivo. (E) Therapeutic effect of intra-articular injection of MT@PLGA-COLBP NPs on early OA mice. (F) Intra-articular injection of melatonin delays the development of OA in mice. Reproduced from Liang et al. (59).

Figure 4

(A) The illustration preparation of NF, PMs and PMs@NF and the clinical application of multifunctional microfluidic PMs@NF. (B) Intra articular injection, in vitro degradation analysis and Calcein AM/DAPI staining of PMs@NF. (C) Characterization of NF functionalized injectable super-lubricating microfluidic PMs. (D) The performance of super-lubricating PMs@NF treat OA model in vivo. (E) Footprints collection of rats 8 weeks postoperatively. (F) Super-lubricating PMs@NF protects cartilage from invariance. Reproduced from Han et al. (64).

Figure 5

(A) The illustration on preparation and application of multifunctional cartilage repair microspheres. (B) Morphological and characterization of microspheres. (C) Microspheres promote chondrogenic differentiation. (D) Microspheres treatment and morphological assessment. Reproduced from Zhang et al. (95).

Figure 6

Proposed clinical research roadmap of PLGA delivery systems for OA therapy.