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. 2021 Jan 5;13(1):60. doi: 10.3390/pharmaceutics13010060

Table 1.

Intra-articular small molecule drug delivery systems for OA treatment, developed in the past 5 years (Acronyms defined at the bottom of the table).

Formulation Drug Carrier Type of Study Main Target Tissue In Vitro Model In Vivo Model Authors;
Year; References
Microparticles Doxycycline PCL Pre-clinical studies Cartilage 3D rabbit chondrocyte agarose model Rabbits Aydin et al.
2015
[44]
Celecoxib PEA Pre-clinical studies Synovium Differentiated HI-60 cells and lysates Human synovium and synovial fluid (ex vivo); rat ACLT model Janssen et al.
2016
[32]
Etoricoxib PCL Pre-clinical studies Synovium, cartilage Not reported Rats Arunkumar et al.
2016
[45]
Lornoxicam Chitosan/TPP Pre-clinical studies Synovium, cartilage Not reported Rat MIA model Abd-Allah et al.
2016
[46]
Fluvastatin PLGA Pre-clinical studies Cartilage Human primary chondrocytes Rabbit ACLT model Goto et al.
2017
[47]
Rhein (cassic acid) PLGA Pre-clinical studies Synovium THP-1 macrophages Not reported Gomez-Gaete et al.
2017
[8]
Kartogenin PLA Pre-clinical studies Cartilage Human synoviocytes Mice DMM model Maudens et al.
2018
[43]
PH-797804, Dexamethasone PLA Pre-clinical studies Synovium Human synoviocytes Mice AIA model Maudens et al.
2018
[48]
Triamcinolone acetonide (Zilretta™) PLGA Phase II/III clinical trials in OA patients 1 Synovium, cartilage Not reported Rat knee model 2 Kumar et al.
2015 2;
Kraus et al.
2018 1
[49,50]
TSG-6 (tumor necrosis factor-alpha stimulated gene-6) Heparin Pre-clinical studies Cartilage Not reported Rat MMT model Tellier et al.
2018
[39]
Fluticasone propionate PVA Pre-clinical studies Synovium Not reported Beagle dogs Getgood et al.
2019
[51]
Celecoxib PLA Pre-clinical studies Synovium Human synoviocytes Not reported Salgado et al.
2020
[52]
Rapamycin PLGA Pre-clinical studies Cartilage Human immortal chondrocytes Mice Dhanabalan et al.
2020
[53]
Nanoparticles VX-745 (p38 MAPK inhibitor) PLA and PLGA Pre-clinical studies Synovium Human synoviocytes Mice AIA model Pradal et al.
2015
[40]
Dexamethasone Avidin/PEG Pre-clinical studies Synovium, cartilage Bovine knee cartilage explants Not reported Bajpayee et al.
2016
[54]
KAFAK (anti-inflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide) pNiPAM-PEG Pre-clinical studies Synovium, cartilage Bovine knee cartilage explants Not reported Lin et al.
2016
[9]
Kartogenin; Diclofenac Chitosan/Pluronic F127 Pre-clinical studies Synovium, cartilage Human BMSCs (bone marrow mesenchymal stem cells); Human primary chondrocytes Rats Kang et al.
2016
[35]
Curcumin PLGA Pre-clinical studies Synovium, cartilage Not reported Rats Niazvand et al.
2017
[55]
Dexamethasone Avidin Pre-clinical studies Synovium Not reported Rabbit ACLT model Bajpayee et al.
2017
[56]
KAFAK pNiPAM-PEG Pre-clinical studies Synovium, cartilage RAW 264.7 macrophages; Bovine knee cartilage explants Not reported McMasters et al.
2017
[57]
CAP (chondrocyte affinity peptide) PEG-PAMAM Pre-clinical studies Cartilage Human primary chondrocytes Rats Hu et al.
2018
[58]
Kartogenin Polyurethane Pre-clinical studies Cartilage Rat primary chondrocytes Rat ACLT model Fan et al.
2018
[59]
Adenosine PEG-b-PLA Pre-clinical studies Synovium, cartilage RAW 264.7 macrophages Rat ACLT model Liu et al.
2019
[60]
Etoricoxib PLGA-PEG-PLGA Pre-clinical studies Synovium, cartilage Human primary chondrocytes Rat ACLT model Liu et al.
2019
[33]
Hyaluronic acid PLGA Pre-clinical studies Cartilage RAW 264.7 macrophages Brine shrimp; Rats Mota et al.
2019
[61]
Hyaluronic acid and near-infrared dye PLGA Pre-clinical studies Cartilage Human primary chondrocytes Mice DMM model Zerrillo et al.
2019
[62]
Celastrol Mesoporous silica Pre-clinical studies Cartilage Rat primary chondrocytes Rat MIA model Jin et al.
2020
[63]
Diacerein PLGA Pre-clinical studies Synovium, cartilage Rat synoviocytes Rat MIA model Jung et al.
2020
[64]
Etoricoxib PLA/Chitosan Pre-clinical studies Synovium MC3T3-E1 cells (mouse osteoblast precursor) Not reported Salama et al.
2020
[65]
MK2i (anti-inflammatory MK2-inhibiting peptide) Linked and non-linked NIPAm Pre-clinical studies Synovium, cartilage Bovine primary chondrocytes Rats Deloney et al.
2020
[66]
Oxaceprol PLGA Pre-clinical studies Synovium Human primary LCLs (lymphoblastoid cell lines) Not reported Alarçin et al.
2020
[67]
Triamcinolone acetonide Dextran sulfate conjugated Pre-clinical studies Synovium RAW 264.7 macrophages; L929 cells (mouse fibroblast) Mice MIA model She et al.
2020
[68]
Hydrogels Amphotericin B Hyaluronic acid/glyceryl monooleate Pre-clinical studies Synovium, cartilage Not reported Rabbits Shan-Bin et al.
2015
[69]
Celecoxib PCLA-PEG-PCLA Pre-clinical studies Synovium Not reported Horse Petit et al.
2015
[34]
Methotrexate/dexamethasone/near-infrared dye Hyaluronic acid + PLGA microcapsules Pre-clinical studies Synovium RAW 264.7 macrophages Rat RA model Son et al.
2015
[70]
Sinomenine hydrochloride Phytantriol Formulation studies Not reported Not reported Not reported Chen et al.
2015
[71]
Dexamethasone Hyaluronic acid Pre-clinical studies Synovium, cartilage Human primary chondrocytes Rat ACLT model Zhang et al.
2016
[72]
PEGylated Kartogenin Hyaluronic acid Pre-clinical studies Cartilage Human BMSCs; human primary chondrocytes Rat ACLT model Kang et al.
2017
[73]
Celecoxib PCLA-PEG-PCLA Pre-clinical studies Synovium Not reported Equine synovitis model Cokeleare et al.
2018
[74]
Dexamethasone Hyaluronic acid/pNiPAM Pre-clinical studies Synovium Human synoviocytes Mice DMM model Maudens et al.
2018
[10]
Triamcinolone hexacetonide (Cingal®) Hyaluronic acid Phase II/III clinical trials in OA patients Synovium, cartilage Not reported Not reported Hangody et al.
2018
[75]
Simvastatin Gelatin Pre-clinical studies Cartilage Mouse primary chondrocytes Mice Tanaka et al.
2019
[76]
Dexamethasone Agarose gel + PLGA microspheres Pre-clinical studies Synovium, cartilage 3D canine articular chondrocyte construct Canine osteochondral autograft model Stefani et al.
2020
[77]
Diclofenac Hyalomer (HA and poloxamer 407) Pre-clinical studies Synovium, cartilage Not reported Rat MIA model Hanafy et al.
2020
[78]
Diclofenac Linked PAPE (2-Pyridylamino substituted 1-phenylethanol) Formulation studies Not reported Not reported Not reported Kawanami et al.
2020
[79]
Eicosapentanoic acid Gelatin Pre-clinical studies Synovium Human primary chondrocytes Mouse DMM model Tsubosaka et al.
2020
[80]
Hyaluronic acid/diclofenac sodium Silica colloidal crystal beads- pNiPAM Pre-clinical studies Synovium, cartilage Human primary chondrocytes Rat DMM model Yang et al.
2020
[81]
Liposomes Quercetin mPEG-PA (Methoxy-poly(ethylene glycol)-l-poly(alanine)) Pre-clinical studies Synovium, cartilage Human primary chondrocytes Rat ACLT model Mok et al.
2020
[82]
Fish oil protein encapsulated in gold nanoparticles DPPC Pre-clinical studies Synovium Not reported Rats Sarkar et al.
2019
[83]
Glucosamine sulphate Distearoyl
phosphocholine		 Pre-clinical studies Cartilage Mouse primary chondrocytes Not reported Ji et al.
2019
[84]
Rapamycin DSPC combined with low-intensity pulsed ultrasound Pre-clinical studies Cartilage Human primary chondrocytes Guinea pigs Chen et al.
2020
[85]

Acronyms: PCL: polycaprolactone; PEA: polyetheramine; PLGA: poly(lactic-co-glycolic acid); PLA: polylactic acid; PVAL: poly(vinyl alcohol); PCLA: poly(ε-caprolactone-co-lactide); PEG: polyethylene glycol; pNiPAM: poly(N-isopropylacrylamide); PAMAM: poly(amidoamine); DPPC: dipalmitoylphosphatidylcholine; DSPC: 1,2-distearoyl-sn-glycero-3-phosphocholine; MIA: monoiodoacetate; AIA: antigen-induced arthritis; ACLT: anterior cruciate ligament transection; DMM: destabilization of medial meniscus.