Surface-Modified Bilosomes Nanogel Bearing a Natural Plant Alkaloid for Safe Management of Rheumatoid Arthritis Inflammation

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory illness affecting the joints. The characteristic of RA is gradual joint deterioration. Current RA treatment alleviates signs such as inflammation and pain and substantially slows the progression of the disease. In this study, we aimed to boost the transdermal delivery of berberine (a natural product) by encapsulating it in chitosan, surface-modified bilosomes nanogel for better management of the inflammation of RA. The chitosan-coated bilosomes loaded with berberine (BER-CTS-BLS) were formulated according to the thin-film hydration approach and optimized for various causal variables, considering the effect of lipid, sodium deoxycholate, and chitosan concentrations on the size of the particles, entrapment, and the surface charge. The optimized BER-CTS-BLS has 202.3 nm mean diameter, 83.8% entrapment, and 30.8 mV surface charge. The optimized BER-CTS-BLS exhibited a delayed-release profile in vitro and increased skin permeability ex vivo. Additionally, histological examination revealed that the formulated BLS had no irritating effects on the skin. Furthermore, the optimized BER-CTS-BLS ability to reduce inflammation was evaluated in rats with carrageenan-induced paw edema. Our results demonstrate that the group treated with topical BER-CTS-BLS gel exhibited a dramatic reduction in rat paw edema swelling percentage to reach 24.4% after 12 h, which was substantially lower than other groups. Collectively, chitosan-coated bilosomes containing berberine have emerged as a promising therapeutic approach to control RA inflammation.

Bilosomes as a promising nanoplatform for oral delivery of an alkaloid nutraceutical: improved pharmacokinetic profile and snowballed hypoglycemic effect in diabetic rats

“…Bilosomes (BLS) are lipid nanovesicles enriched by bile salts with a superior ability to penetrate biological membranes (Elkomy et al, 2022 ). Bile salts hinder the breakdown of nanocarriers in the gastrointestinal tract (GIT), hence improving penetration, which is advantageous for oral administration (Waglewska et al, 2020 ; Elkomy et al, 2022 ). Furthermore, the inclusion of certain bile salts, such as sodium deoxycholate (SDC), improves the colloidal stability (Elkomy et al, 2022 ).…”

Intranasal Delivery of Granisetron to the Brain via Nanostructured Cubosomes-Based In Situ Gel for Improved Management of Chemotherapy-Induced Emesis

“…Using the plot3D package in R software, 3D surface graphs are plotted [ 24 , 25 ]. The optimization was set to minimum size and maximum surface charge and entrapment to obtain the formula with the maximum desirability [ 26 , 27 ].…”

“…The GS levels in the supernatant portion were estimated spectrometrically at 302 nm. The EE percentage was calculated using the following equation [ 26 , 27 ]: …”

“…The GS levels in the supernatant portion were estimated spectrometrically at 302 nm. The EE percentage was calculated using the following equation [26,27]: EE% = (GS added (10 mg) − Free GS in supernatant) GS added (10 mg) × 100…”

Polysaccharide-Based Transdermal Drug Delivery

“…The positive charge and bioadhesive properties of BER-CTS-BLS allowed the permeability coefficient of BER-CTS-BLS to be 1.5 times higher than that of BER solution, achieving better drug diffusion. BER-CTS-BLS gel significantly decreased the swelling percentage of rat paw edema after 12 h, providing a new therapeutic approach for the treatment of RA [ 196 ]. Cationic starch and poly (vinyl alcohol) (PVA)-based films loaded with MTX were used for the treatment of RA, avoiding the intestinal side effects caused by MTX.…”