Table 6.
Active-targeting nanomaterials for drug delivery to synovium or synoviocytes
| Nanomaterial type | Targeting modality | Physical properties | Animal model | Major findings | Ref. |
|---|---|---|---|---|---|
| Alginate nanoparticles decorated with tuftsin peptide and loaded with IL-10 plasmid DNA | Active (surface receptor) | ~300nm | In vivo rat (adjuvant-arthritis model) | Targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state. | [137] |
| Self-assembling block copolymer with protein-tethering moiety (IL-1Ra) | Active (IL-1 surface receptors) | 270nm ± 5nm |
In vitro rabbit synoviocytes In vivo rat (healthy) |
IL-1Ra-tethered particles bound to synoviocytes via the IL-1 receptor and significantly increased whole joint retention of IL-1Ra relative to soluble IL-Ra. | [75] |
| Micelle carriers of camptothecin, surface modified by vasoactive intestinal peptide | Active (surface receptors) | Not reported | In vivo rat (CIA RA model) | Single subcutaneous injections of the micelles led to mitigated inflammation in joint if CIA mice up to ~4.5 weeks after induction. | [139] |
| RGD peptide–exposing long circulating PEG liposomes loaded with dexamethasone and targeted to αvβ3 integrins expressed on angiogenic VECs | Active (surface receptors) | 100nm |
In vitro HUVECs In vivo rats (AIA RA model) |
In vivo, increased targeting of radiolabeled RGD-PEG-L to areas of LPS-induced inflammation in rats was observed. | [158] |
| αvβ3-targeted fumagillin nanoparticles | Active (surface receptors) | 250nm | In vivo rats (K/BxN model of RA) | Synovial tissues from animals treated with targeted fumagillin nanoparticles showed a significant decrease in inflammation and angiogenesis, and preserved proteoglycan integrity. | [157] |
| Nanocarrier composed of lipids, PEG-PLGA forming a hydrophilic shell, folic acid around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core and loaded with methotrexate | Active (surface receptors) | 133.6 – 208.5nm (varied based on composition of components) |
In vitro RAW 264.7 cells In vivo rats (AIA RA model) |
Folate targeted particles demonstrated superior uptake in RAW 264.7 cells than untargeted cells. A smaller paw size and decrease swelling was observed in the AIA model of rat when injected with the targeted particles than the untargeted particles. | [156] |
| PLGA nanoparticles coated either with macrophage-derived microvesicle proteins or red blood cell membrane proteins and loaded with tacrolimus | Active (surface receptors) | 130nm |
In vitro HUVECs In vivo rats (CIA RA model) |
In vitro binding of the microvesicle coated particles was greater than controls. The microvesicle coated particles also showed greater therapeutic impact in CIA model than controls. | [159] |
AIA = Antigen-induced arthritis; CIA = Collagen Induced Arthritis; HUVEC = Human umbilical vein endothelial cells; IL-1Ra = Interleukin 1 Receptor Antagonist; LPS = Lipopolysaccharide; MPCM = Mouse peritoneal cavity macrophages; PEG = poly (ethylene glycol); PLGA = poly (lactic co-glycolic acid); RA = Rheumatoid Arthritis; RAW 264.7 = Macrophage-like cell line derived from tumors induced in male BALB/c mice by the Abelson murine leukemia virus; RGD = arginine-glycine-aspartic acid; VEC = Vascular Endothelial Cells.