Transdermal delivery system of nanostructured lipid carriers loaded with Celastrol and Indomethacin: optimization, characterization and efficacy evaluation for rheumatoid arthritis

Abstract

Co-encapsulation of drugs provides a convenient means for treating different symptoms of a disease. Celastrol (Cel) shows potent anti-arthritic activity and Indomethacin (Indo) is effective in relieving inflammatory pain. Nanostructured lipid carriers loaded with Celastrol and Indomethacin (Cel-Indo-NLCs) were prepared by emulsification evaporation-solidification method, optimized by the Box-Behnken design and characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) and powder X-ray diffraction analysis (PXRD). Visualization of transdermal translocation of Cel-Indo-NLCs was achieved by confocal laser scanning microscope (CLSM). Further, Cel-Indo-NLCs were incorporated into Carbopol 940 for transdermal delivery. The in vitro studies were evaluated by using the Franz diffusion cells. Cel-Indo-NLCs depicted small particle size (26.92 ± 0.62 nm) and PDI (0.201 ± 0.01), high entrapment efficiency (96.56 ± 1.41%) and drug load (3.65 ± 0.05%). Moreover, Cel-Indo-NLCs showed prominent effect of decreasing paw oedema, inhibiting inflammation and pain by regulating the levels of IL-1b, TNF-a, b-endorphin and Substance P. After the administration of Cel-Indo-NLCs-gel, no skin irritation was observed in rats. There was no difference of gastrointestinal tract between different groups of rats when they were sacrificed. The histological analysis showed no renal and reproductive toxicity. Therefore, it can be concluded that co-encapsulation strategy based NLCs have the potential to provide safe transdermal delivery and are promising in treatment of pain and inflammation associated with rheumatoid arthritis.

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

“…[101,102] Silybin Hepatotoxicity [103,104] Bifendate Hepatitis [105,106] Buprenorphine Analgesic treatment of chronic pain and opioid dependence. [107,108] Dexamethasone acetate Anti-inflammatory [109] Topical Cyproterone acetate Acne vulgaris [110] Acitretin Acne vulgaris and psoriasis [73,111] Psoralen Psoriasis [29,112] Flurbiprofen Rheumatoid arthritis, sunburn and gout [113,114] Ketoprofen Arthritis and skin inflammation [30,115] Celastrol/Indomethacin Arthritis and inflammatory pain [116] Celecoxib Anti-inflammatory [43] Valdecoxib Anti-inflammatory [117] Fluticasone Atopic dermatitis and psoriasis [42] Lidocaine Local anesthetic [118] Benzocaine/Lidocaine Local anesthetic [119] Nanolipid Q 10 CL Anti-aging/cellular antioxidant [58,[120][121][122] Lutein Antioxidant, anti-stress, and blue light filter protect the skin from photo damage [123,124] Meloxicam Osteoarthritis and rheumatoid arthritis [125] Clotrimazole Antifungal [26,126] Octyl-methoxycinnamate UVB absorber, Sunscreen [127,128]…”

Celastrol Niosome Hydrogel Has Anti-Inflammatory Effect on Skin Keratinocytes and Circulation without Systemic Drug Exposure in Psoriasis Mice

“…The EE% and drug loading capacity (DL) of Cel Nio were quantified with ultrafiltration. 16 Briefly, the centrifuge condition of Cel Nio was set at 4000 × g for 30 min in a centrifuge tube with a 30-kDa ultrafilter. The total Cel in the solution of Cel Nio (W total ) and the free Cel (W free ) were diluted in For the investigation of the morphology of Cel Nio, transmission electron microscopy (TEM, Hitachi TEM system, Japan) was used.…”

“…14 TwHF has been reported to have anti-inflammatory and immunosuppressive effects, which has been applied for the therapy of rheumatoid arthritis and psoriasis vulgaris. 15,16 Celastrol (Cel), a triterpenoid obtained from TwHF with a molecular weight of 450.6 g/mol, has anti-inflammatory and anticancer properties, 17 which can limit the production of Th17-related cytokines and chemokines. 18 Despite its promising anti-inflammatory and anticancer effects, Cel has also been reported to induce toxicity, as indicated in the weight loss of treated mice.…”

Celastrol Nanoemulgel Formulation and in Vitro Penetration Test

“…The method was developed into peroral, IP, and topical routes. The study results concluded that Celastrol developed into nanotechnology increased the absorption efficiency (EE) to 98.06% with an average particle size of 89.6±7.3 nm ≤100 nm and zeta potential of 87.8±5.8 mV [4][5][6][7][8].…”