Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

Abstract

Osteoarthritis is the most prevalent chronic and debilitating joint disease, resulting in huge medical and socioeconomic burdens. Intra-articular administration of agents is clinically used for pain management. However, the effectiveness is inapparent caused by the rapid clearance of agents. To overcome this issue, nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic agents. Given the therapeutic programs are inseparable from pathological progress of osteoarthritis, an ideal delivery system should allow the release of therapeutic agents upon specific features of disorders. In this review, we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug release. Then, we review the interactions of nanoparticles with cartilage microenvironment and the rational design. Furthermore, we highlight advances in the therapeutic schemes according to the pathology signals. Finally, armed with an updated understanding of the pathological mechanisms, we place an emphasis on the development of “smart” bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological signals. We anticipate that the exploration of nanoparticles by balancing the efficacy, safety, and complexity will lay down a solid foundation tangible for clinical translation.

The advances in nanomedicine for bone and cartilage repair

“…Nanoparticles (NPs) are microscopic particles manufactured from inorganic or organic materials up to 100 nm in size [ 13 ], which can be modified based on the specific requirement to achieve targeting delivery, stimulus responsiveness, and enhanced biocompatibility, optimizing their potential as targeted therapeutic carriers.…”

“…In addition, advances in nanomaterials have led to the development of a series of biomimetic scaffolds with nanostructures that enhance cell proliferation/migration and homing effects by simulating the natural bone hierarchy and extracellular matrix (ECM), to promote the regeneration of injured tissues [ 12 ]. Moreover, nanoparticles (NPs) and extracellular vesicles (EVs), as drug delivery vehicles, can minimize the dosage, increase the half-time and have the capacity to be modified, achieving targeted therapy for various types of osteochondral lesions [ 13 ]. Hence, the development of nanomedicine has significantly enhanced the diagnostics and therapeutics for cartilage and bone disease.…”

Knee Osteoarthritis Therapy: Recent Advances in Intra-Articular Drug Delivery Systems

“… 86 By adjusting the physicochemical properties or decorating with moieties, NPs can be modified with functional groups to target the components and/or cells in the cartilage. 87 This section reviews the current developments and novel applications of OA-related NP-based DDSs, including liposomes, micelles, dendrimers, polymeric nanoparticles (PNPs), and exosomes. 51 , 88–92 …”

A Review of the Use of Microparticles for Cartilage Tissue Engineering

“…They are small enough to be delivered in a minimally invasive way through a syringe and needle, such as with the microspheres used for controlled release of drugs, but they are also large enough to provide a surface for cells to grow on, particularly in the case of microcarriers, or to build up 3D structures in the case of granular hydrogels. In the context of cartilage TE, the use of biomaterial scaffolds, including those based on hydrogels [24][25][26], as well as the use of nanomaterials, particularly nanoparticles used for controlled delivery [27,28], have been extensively and recently reviewed elsewhere.…”