Table 1.

Drug delivery systems for OA treatment

Nanocarrier	Drug	Cell line/Animal model	Major outcomes	Refs
PLGA nanoparticle	WYRGRL peptide	Model of OA	Biodegradable and specific binding to the cartilage tissue	[134]
PEG poly (NIDAM) NPs	KAFAK	OA model	Effective drug delivery and inhibiting the pro-inflammatory IL-6 expression	[135]
Niosome	Date seed oil	Cg-induced paw edema	Good stability, nano-size range, and great anti-inflammatory activity	[136]
Bisphosphate nanoparticle	Clodronate	Circulating progenitor cells (CPCs) OA model	Upregulation of SOX9 gene expression upon treatment, decreased osteoarticular pain, and improved mental and physical performance	[137]
PVCL-co-acrylic hydrogels	Sodium diclofenac	–	Sustained permeation through an artificial skin membrane and high drug delivery	[138]
Lipid nanoparticle	Ibuprofen	Male SKH-1 hairless mice	High entrapment efficiency (95.51%), high permeation, and potential anti-inflammatory activity	[139]
PLGA nanoparticle	IL-1 receptor antagonist (IL-1Ra)	NF-KB inducible reporter cell line	Tunable size (300-700 nm), cytocompatible, good stability, and efficient inhibition of IL-1β signaling	[140]
AuNPs	Chondroitin sulfate	Primary goat chondrocytes	High increase in GAG and collagen production, stimulating chondrocyte proliferation, and enhancing extracellular matrix production	[141]
Chitosan NPs	Berberine	Rat knee OA model	Spherical shape, good stability, ideal releasing profile, increased retention time in synovial fluid and high anti-apoptotic activity	[20]
Solid lipid NPs	Aceclofenac	Albino rat	Good particle size (143.4–154.2 nm), prolonged drug release, high uptake, and great anti-inflammatory activity	[12]
Lipid NPs	Diacerein	Rat model of OA	Good particle size (396 nm), sustained release, high delivery, and improved histopathology analysis	[142]
Lipid NPs	Diacerein	Rat	Good particle size (270 nm) and zeta potential (− 13.78 to − 19.66 mV), high entrapment efficiency (88.1%), sustained drug release, and decreased side effects of diacerein	[143]
NPs-in-microspheres	Brucine	Rats	High biocompatibility, prolonged drug release, high residence in articular cavity, and improved retention	[14]
Polymeric NPs	KAFAK	THP-1 cells Cartilage plugs	Decreased pro-inflammatory cytokine and selective targeting	[144]
Polymeric NPs	Curcumin	Human primary chondrocytes	Inhibiting mRNA expression of pro-inflammatory mediators (IL-1β; TNF-α; MMPs 1, 3, and 13), decreasing OA disease progression, reducing proteoglycan loss, and decreasing synovitis	[145]
PEGylated NPs	KAFAK	Chondrocytes	Efficient targeted delivery and decreasing inflammatory reaction	[146]
Polymeric NPs	IL-1Ra protein	Synoviocytes Rat stifle joint	Good particle size (300 nm), maintaining bioactivity, specifically targeting synoviocytes, increased retention time, and decreasing inflammatory factors	[19]
Bipolymeric NPs	Dextran FITC	Healthy rat knees	No decrease in proteoglycans biosynthesis and induction no inflammatory response	[147]
PLGA NPs	Dexamethasone	Synovium and articular damage	Excellent biocompatibility, internalization via phagocyte process and stimulation of inflammation	[148]
Polymeric NPs	Curcumin	Rat model of OA	Enhancing cellularity and matrix and high biocompatibility	[149]
Coiled-coil protein	BMS493	Human articular chondrocytes	Reducing mRNA levels of MMP-13 and IL-1β	[150]
Ginger extract nanoparticle	–	Patients with knee OA	Improving knee joint pain, symptoms, daily activities, and quality of life	[151]
Solid lipid NPs	Diacerein	–	High encapsulation of diacerein, prolonged release behavior, increase in diacerein payload and thermoresponsive drug delivery	[152]
Amine terminal polyamidoamine (PAMAM) dendrimres	Insulin-like growth factor 1 (IGF-1)	Rat OA	Promoting pharmacokinetics and potential of disease-modifying OA drugs	[153]
Nanocrystals-polymer particles	–	Human OA synoviocytes and murine mechanistic OA model	Lack of effect on mitochondrial activity, exerting protective effect on the cartilage and epiphysis of the medial tibia, and significant reduction in VEGF and Adamts5 expression	[154]
Nanocrystal-polymer particles	P38a/b MAPK inhibitor PH-797804	OA model and human OA synoviocytes	Lack of toxicity against human OA synoviocytes, decreasing inflammation and joint destruction and also excellent retention and function at the target site	[155]
Self-assembled thermoresponsive nanostructures of hyaluronic acid		OA mouse model	High biocompatibility and significant sustained residence time at the injection site, reduction of inflammatory cytokines and efficacy in delivery of peptides, proteins or small molecules	[156]
Poly (ester-amide) particle	Celecoxib	Ovine model	High biocompatibility, no toxic effect at the injection site, and great diffusion into neighbor tissues	[157]
HA-PLGA particles	–	RAW264.7 macrophage cells and Wistar rats	Great safety and high anti-inflammatory effect	[158]