Table 2.
Lipid nanostructures encapsulating natural compounds with anti-inflammatory activity.
| Natural Compound |
Lipid Nanostructure |
Composition | Administration | Activity [Reference] |
|---|---|---|---|---|
| Polysaccharides | ||||
| GLU | Liposomes | DSPC:GLU 8:2 (molar ratio) |
In vitro studies in primary mouse chondrocytes | Accelerated cell viability and proliferation; down-regulation of pro-inflammatory cytokines; up-regulation of anabolic components [151] |
| CS | Positive Liposomes | PC:DOPE:Chol:SA 4:2:3:1 (molar ratio) Size—170.3 nm; PDI—0.218; ζ—10.44 mV |
In vitro studies in stressed L929 mouse fibroblasts | Protective effect against oxidative damage and decrease of pro-inflammatory cytokines production [152] |
| CS | Positive liposomes embedded in type I collagen and freeze-dried | PC:DOPE:Chol:SA 4:2:3:1 (molar ratio) E.E.—68.2% Size—523.83 nm; PDI—0.40; ζ—10.44 mV |
L929 mouse fibroblasts injected in sterile freeze-dried matrices | Better control of CS release compared to liposomal CS; allowed cell penetration for regenerative activity [153] |
| CS and GLU | Liposomes | Epikuron 200©, Epikuron 200© SH |
Oral administration to rabbits | High permeation through intestinal mucosa; no histopathological alterations of the intestinal tissue [154] |
| CS and tapentadol | CS surface modified nanovesicles | PC:Chol:SA 7:3:1.5 (molar ratio) |
Sublingual administration in OA-induced Wistar rats | Improved bioavailability and reduction of pain [155] |
| CS and diacerein | CS modified SLN | Lecithin:SA 1:6.25 (mass ratio) |
IA administration in femoro-tibial joint of rat knee | Increased drug bioavailability [156] |
| HA | Liposomes | PC: HA solution (1:1, volume ratio) | Surface force balance measurements | The model suggested that multiple lipid layers formed on the surface increased lubrication, while HA could be complexed by lipids in the synovial fluid [125] |
| HA and celecoxib | Liposomes embedded in HA gel | PC:Chol 5:1 (mass ratio) |
Single IA administration in rabbit OA knee model | Effective in pain control and cartilage protection [157] |
| Proteins | ||||
| Leech saliva extract rich in proteins and peptides | Liposomes | PC:Chol 95:5 (mass ratio) |
Topical administration in human OA patients for 1 month | Enhanced skin absorption; 50% pain relief; reduction of joint inflammation and stiffness [158] |
| Lactoferrin | Positive MVL (Multivesicular liposomes) Liposomes |
DPPE:Chol:SA 5:5:1 (molar ratio) |
IA administration in CIA DBA1 mice | Prolonged the residence time for better reduction of inflammation, compared to free lactofferin; decreased pro-inflammatory cytokines production (TNF-α, IFN-γ); increased anti-inflammatory cytokines (IL-5, IL-10) [23,150] |
| Polyphenols | ||||
| Quercetin and resveratrol |
Liposomes | Lipoid S75:oleic acid 10:1 (mass ratio) |
Oxidative stressed fibroblasts | High cellular uptake and superior ROS scavenging, compared to free polyphenols [159] |
| Resveratrol and curcumin | Lipid-core nanocapsules | Polycaprolactone:seed oil:sorbitan stearate 1:1.65:0.385 (mass ratio) |
In vitro model of human primary chondrocytes treated with nitric oxide-donor to mimic OA joint conditions | Higher dose delivery, protective effect on cell morphology and membrane surface [30] |
| Morin | Mannose decorated Liposomes | DSPC:Chol: F-DHPE 60:35:5 (molar ratio) |
Arthritic rats treated intravenously for 3 days | Preferential internalization into macrophages, inhibited the osteoclastogenesis, pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17), VEGF angiogenic factor and iNOS inflammatory enzyme production; suppressed RANKL and STAT-3 expression, but increased osteoprotegerin expression [160] |
| p-Coumaric acid | Mannose decorated Liposomes | DSPC:Chol:mannose 60:35:5 (molar ratio) |
Ex vivo studies in macrophages; arthritic rats treated intravenously, for 3 days | Targeted synovial macrophages, inhibited osteoclasts differentiation, suppressed expression of MMP-9 and inflammatory cytokines [161] |
| Oxymatrine | Positive MV liposomes | EPC:Chol:DSPE-PEG 4:1:1 (mass ratio) E.E.—73.4%; Size—178 nm; PDI—0.167; ζ—13.30 mV |
Intraperitoneal administration in intervertebral disc degeneration (IVDD) mice model | Reduced the mRNA and protein level of MMP3, MMP-9 and IL-6 [92] |
| Curcumin | Liposomes | PC:Chol 30:70 (molar ratio) |
In vitro studies in 7F2 osteoblasts and RAW 234.7 macrophages | High cellular uptake, favored osteoblast differentiation and mineralization, increased OPG:RANKL ratio and prevented osteoclastogenesis [162] |
| Curcumin | Liposomes | Lecithin:Chol 18:1 (molar ratio) |
Sistemic administration in C57BL/6J mice with hemi-lung radiation | Inhibited NF-kB pathway, down-regulated pro-inflammatory cytokines TNF-α, IL-6 and IL-8, and TGF-β [163] |
| Curcumin | Liposomes | DMPC:DMPG:Chol 7:1:8 (molar ratio) |
In vitro studies of liposomal curcumin in human blood, plasma and culture medium of human lymphocytes, splenocytes and virus-transformed human B-cells | Higher stability and inhibitory effects on concanavalin A-stimulated human lymphocytes, splenocytes and B-cells proliferation; better bioavailability and efficacy, compared to free curcumin, recommending its clinical application [164] |
| Curcumin (curcuminoids) | Exosomes | Exosomes: curcumin 1:2:9 (mass ratio) |
In vitro studies in RAW 264.7 macrophages and in vivo studies in C57BL/6J mice with oral administered or injected system | Increased bioavailability and anti-inflammatory activity of curcumin [165] |
| Dimethyl curcumin | Liposomes | PC:Chol 4:4 (molar ratio) |
IA injections (six times) in CIA rats model | Regulated gelatinases release and cell cycle of spleen lymphocytes [166] |