Research progress on biodegradable polymer-based drug delivery systems for the treatment of knee osteoarthritis

Abstract

Knee osteoarthritis (KOA) is a disease that involves multiple anatomical and physiological changes in the knee tissues, including cartilage degeneration, bone remodelling and formation of bony encumbrances, which leads to clinical manifestations including pain, stiffness, swelling and limitation of knee function. Knee osteoarthritis is a chronic joint disease characterised by degenerative cartilage lesions and secondary osteophytes in the knee joint. The symptoms of knee osteoarthritis tend to progress slowly, and at this stage, the number of patients with KOA is increasing. However, due to the adverse effects and poor therapeutic outcomes following surgical treatment, intervention therapy through the utilisation of biodegradable polymeric materials is required. Currently, clinical aspects are mainly used to treat cartilage degeneration in patients with osteoarthritis of the knee by using different kinds of biodegradable biopolymer materials with excellent physical properties, histocompatibility and other properties, combined with a drug delivery system, which can reduce the level of inflammation and stiffness in the focal area, and maximise the restoration of the patient's knee joint joint mobility and athletic ability. Based on the properties of the polymeric material drug delivery system, the polymeric material has a variable drug loading capacity that encapsulates hydrophobic/hydrophilic drugs and controls the release kinetics by regulating the composition and charge. This paper reviews the research progress of Poly (ε-caprolactone) (PCL), Poly(lactic acid) (PLA), Poly (lactic glycolic acid) (PLGA), Poly(ethylene glycol) (PEG) synthetic polymers and collagen, chondroitin sulfate, other natural polymers based drug delivery systems for the treatment of knee osteoarthritis, and explains that different biodegradable polymeric materials have been widely used for the treatment of knee osteoarthritis. However, there are still issues of degradability, toxicity, compatibility, and durability and safety of the drug delivery system of degradable materials that need to be addressed in further clinical trials. As biodegradable biomedical materials continue to be explored, eventually idealized polymeric materials will stand out in the treatment of KOA.

Keywords: biodegradable polymers; drug delivery system; knee osteoarthritis; natural polymers; synthetic polymers; treatment.

Application of different polymers in the treatment of knee osteoarthritis.

FIGURE 1

(A) Flurbiprofen thermal gel has similar short-term analgesic effect on OA rats. Based on the CatWalk test of paw print intensity on the contralateral healthy side and the ipsilateral affected OA side (affected), the (B) TIPPI percentage and (C) knee flexion scores of the four experimental groups before and 2 h after the first dose of the drug. CC BY 4.0. Copyright 2020 The Author(s).

FIGURE 2

(A) Intra-articular injection of adenosine-conjugated NPs reduces knee joint swelling; (B) Histological analysis shows less cartilage protection, proteoglycan loss and reduced OARSI scores in nanoAdo-treated rats compared to rats treated with the carrier; (C) Reconstruction of the µCT data reveals a reduction in cartilage surface damage. CC BY 4.0. Copyright 2019 The Author(s).

FIGURE 3

(a) Representative in vivo fluorescence superimposed on an X-ray image of a mouse (Source intensity ranges from 0 to 2,450 pmol m⁻¹ cm⁻¹); (b) Percentage of in vivo fluorescence in mice normalised after IA injection of KGN-NPPs; (c) Representative H&E paraffin-embedded tissue light (right) and fluorescence (right) micrographs of mouse lateral knee KGN-protein; (d) Percentage ratio of medial to lateral tibial epiphyseal thickness at Day 56; (e) Multiplexed enzyme-linked immunosorbent assay (ELISA) analysis of VEGF in mouse plasma at Day 56. CC BY 4.0. Copyright 2018 The Author(s).

FIGURE 4

IA drug solutions, conventional NPs and E30-NPs dosed at 0.2 mg/kg administered at 12 and 24 h.Note: Vertical bars indicate mean ± standard deviation (n = 6). Statistical analysis was performed using the StudentStudentt test (*P < 0.05 for drug solutions; **P < 0.05 for conventional NPs). E30-NPs, NPs prepared with PLGA and Eudragit RL. CC BY 4.0. Copyright 2016 The Author(s).

FIGURE 5

(A) Representative confocal images of MT@PLGA and MT@PLGA-COLBP in chondrocytes; (B) Detection of FITC-labelled COLBP signals in chondrocytes by flow cytometry; (C) Penetration of MT@PLGA-COLBP in free mouse knee joints; (D) IVIS photographs of MT@ICG-PLGA and MT@ICG-COLBP in mouse knees; (E) Analysis of ROI fluorescence intensity in IVIS images. Data are expressed as SD ± mean: **p < 0.01, ***p < 0.001. CC BY 4.0. Copyright 2023 The Author(s).

FIGURE 6

(A) Macroscopic observation of cartilage after 4 weeks of PCL/PEG-Nar nanofibre membrane treatment; (B) Macroscopic scoring of cartilage after 4 weeks of PCL/PEG-Nar nanofibre membrane treatment; (C) H&E staining and (D) Saffronin O/fast green staining, Scale bar: 800 μm; (E) Evaluation of OARSI score after 4 weeks of PCL/PEG-Nar nanofibre membrane treatment. CC BY 4.0. Copyright 2022 The Author(s).

FIGURE 7

(a) Expression of angiogenesis-related genes PDGF-BB, TGF-β, MMP-9 and Ang detected by qRT-PCR; (b) Quantification of PDGF-BB determined by ELISA; (c) Effect of PDA-PEG NPs on T-tubule formation; (d) Effect of PDA-PEG NPs on cell migration (n = 3) Notes: ‘*’ indicates p < 0.05, “**” indicates p < 0.01, and NS indicates not significant. CC BY 4.0. Copyright 2022 The Author(s).