This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUC_brain/AUC_blood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy.

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.

The aim of this research is to formulate a lecithin–chitosan based nanoparticulate system loaded with berberine (BER-LC-CTS-NPs) that could be integrated into a topically applied formulation and assessed for healing wounds in a diabetic animal model. In order to formulate BER-LC-CTS-NPs, soybean lecithin, isopropyl myristate, and berberine dispersed in ethanolic solution were added into an aqueous solution of chitosan dropwise with sonication. We assessed the influence of lecithin amount, chitosan amount, and isopropyl myristate concentration on particle diameter, zeta potential, and entrapment and employed a Box–Behnken statistical design. The resulting optimized BER-LC-CTS-NPs had a mean size of 168.4 nm, a surface charge of 33.1 mV, and entrapment of 82.3%. The optimized BER-LC-CTS-NPs showed a sustained in vitro release profile. Furthermore, the potential of the optimized BER-LC-CTS-NPs integrated into a topical gel formulation for wound healing in streptozocin-induced diabetic rats was assessed. Our findings show that combining chitosan and berberine in the nanoparticles produces a synergistic effect when it comes to wound healing. The optimized nanoparticulate system works by reducing inflammation, inducing blood vessels and fibroblast proliferation, and promoting mature collagen fibers deposition. Based on the experimental results, lecithin–chitosan nanoparticles loaded with berberine have evolved as a promising strategy for accelerating wound the healing process in diabetic patients. However, the clinical merits of the developed system need to be investigated in diabetic patients.

Purpose: This study aimed to formulate citicoline-loaded chitosan-coated liposomes (CT-CS-LPs) for topical administration and evaluated for wound healing in a diabetic animal model. Methods: CT-LPs were formulated via a thin-film hydration approach and coated with chitosan (CS). Box-Behnken statistical design investigated the effects of lipid amount, chitosan concentration, and cholesterol amount on vesicle diameter, surface charge, and entrapment efficiency. The potential of the optimized CT-CS-LPs gel for wound healing was further evaluated in streptozocin-induced diabetic rats. The different healing stages were evaluated by several techniques, including general and special staining techniques, in addition to antibody immunohistochemistry. Results: The optimized CT-CS-LPs obtained had a mean size of 211.6 nm, a 50.7% entrapment efficiency, and a positive surface charge of 32.1 mV. In addition, the optimized CT-CS-LPs exhibited in vitro sustained release behavior. The in vivo experiments revealed that treatment with the optimized CT-CS-LPs boosts the healing process of the skin wound in diabetic rats by reducing inflammation, accelerating re-epithelization, angiogenesis, fibroblast proliferation, and connective tissue remodeling, leading to rapid wound closure. Conclusion: Chitosan-coated liposomes containing citicoline have emerged as a potential approach for promoting the healing process in diabetic rats. However, the therapeutic effectiveness of the suggested approach in diabetic patients needs to be investigated.