Table 1.
Hydrogels for the delivery of drugs/bioactive agents used in the treatment of RA
| Delivery vehicle | Drugs/Agents | Conditions | Main results | Reference |
|---|---|---|---|---|
| Chitosan hydrogels combined with alginate microspheres | Diclofenac |
In vivo study New Zealand rabbits (3 weeks post-treatment) |
The anti-inflammation efficacy of the combined hydrogels in rabbits with RA was higher than that of drug solution and pure chitosan hydrogels | [38] |
| Cationic agarose hydrogels | ASO |
In vivo study AA CLA CIA |
Alleviating inflammation and tissue destruction were demonstrated in more than 90% of the testing animals reduction of central inflammatory cytokines and decrease of joint swelling and tissue damage | [43] |
| Fibrin gel (FGB) and PLGA-PEG-PLGA hydrogel (HGB) | BMMSCs | In vivo study OVA rabbits (12 weeks post-treatment) |
The administration of BMMSCs reduced inflammatory cytokine levels and improved joint swelling in both groups The preservation of adjacent cartilage and enhanced cartilage repair were detected |
[47] |
| Nanofibrous hydrogel | MMP-2 and MMP-9 |
In vivo study Balb/C mice (8 weeks post-treatment) |
The results showed that nanofibrous gels could persist stably after injection into healthy joints of mice in vitro studies showed that release loaded agents in response to synovial fluid from arthritic patients |
[44] |
| Microemulsion-based topical hydrogels | TNX |
Ex vivo study Laca Mice Sprague–Dawley (48 h post-treatment) |
Microemulsion formulations demonstrated be superior in controlling inflammation as compared to traditional topical dosage forms and presented efficacy equivalent to the oral formulation | [48] |
| NLCs | MTX |
In vivo study Wistar rat (24 h post-treatment) |
The immunocytochemistry to detect IL-6 expression and immunofluorescence assay showed that promoted apoptosis occurred in an in vitro arthritis model treated with NLCs-MTX. It was verified decreased inflammation and activated apoptosis promoted by MTX encapsulated NLCs in rheumatoid arthritic cells Histopathological analysis of skin suggested the safety potential of NLCs |
[49] |
| MTX-NLCs + CE hydrogel | MTX |
In vivo study CFA induced arthritis rat (17 weeks post-treatment) |
MTX-NLCs + CE hydrogel significantly decreases the inflammation in RA animal model | [50] |
| Lipogel and hydrogel microemulsion | Diflunisal |
Ex vivo study Human abdominal skin (24 h post-treatment) |
The lipogels delivered a significant amount of drug through the skin than the hydrogel. The constitution of lecithin showed to affect the skin permeability increasing the capability of the lipogel |
[51] |
| TG-18 hydrogel | TA |
In vivo study K/BxN serum-transfer model of IA (14 days post-treatment) |
In arthritic mice, hydrogel encapsulated with a fluorescent dye showed flare-dependent disassembly assessed as a loss of fluorescence. A unique dose of TA-encapsulated hydrogel decreased arthritis manifestation in the injected paw |
[46] |
| Aspasome hydrogel | MTX |
In vivo study AIA in Wistar rats (21 days post- treatment) |
Transdermal application of methotrexate-loaded aspasome hydrogel in model disease demonstrated a more significant decrease of rat paw diameter, tumor necrosis factor-alpha (TNF-α), interleukin (IL-1) β, cartilage damage, inflammation, pannus formation, and bone resorption when compared to arthritic control rats The group treated with free methotrexate exhibited intermediate effects however, the group treated with free aspasome did not show to have an effect |
[52] |
| Propyl-capped PCLA-PEG-PCLA gel | Celecoxib (40 mg/g and 120 mg/g) |
In vivo study Dutch Warmblood horses (5 weeks post-treatment) |
One intra-articular injection of LCLB-gel or HCLB-gel demonstrated a sustained and controlled intra-articular release in healthy and inflamed joints The celecoxib formulations presented a soft effect on inflammatory and synovial fluid biomarkers, but these returned to threshold 1 week after administration high levels of celecoxib were detected in the joint after 1 month, but no overall anti-inflammatory effects was observed, maybe due to the moderate synovitis There were no adverse effects during the study period |
[39] |
| Scv gel | NO |
In vivo study collagen-induced arthritis mouse model (35 days post- treatment) |
The NO-Scv gel decreased inflammation levels and showed good biocompatibility Therapeutic effect of the NO-Scv gel in decreasing the onset of RA is observed in a mouse RA model when compared to the effects of dexamethasone alone |
[40] |
| DLTH with chitosan–glycerin–borax | Dexamethasone |
In vivo study Collagen-induced arthritis wistar rats (3 weeks post-treatment) |
Paw swelling, arthritis scores, and joint inflammation destruction were reduced in the group treated with DLTH DLTH demonstrated down-regulated serum IL-17A and mRNA levels of inflammatory factors DLTH-treated rats elucidated the pain-reducing effects of DLTH |
[41] |
| Hydrogel formulations (Poloxamer 407 and chitosan) loaded PLGA and PCL nanoparticles | DS | In vitro study | After 1-month prolonged in vitro release of DS was reached by using polymeric nanoparticles with in situ hydrogels | [42] |
| HA-AC hydrogels | Iguratimod |
In vivo study CIA rats (21 days post-treatment) |
The results demonstrated superior bioavailability and longer half-life time with NanoIGUR-loaded hydrogel than traditional iguratimod Animal experiments for 21 days showed that subcutaneous injection of NanoIGUR-loaded hydrogel (10 mg/kg every 3 days) and traditional iguratimod (10 mg/kg daily) exhibited identical efficacy in diminishing arthritis index score, pathological score, and expression of inflammatory cytokines |
[45] |