Olanzapine (OL) is atypical antipsychotic drug which suffers from an extensive hepatic metabolism and poor bioavailability. In addition, it has low brain permeability due to efflux by P-glycoproteins. In the current investigation, surface modified niosomes containing OL were prepared for brain targeting of drug through nasal route. Spans were mixed with cholesterol at ratios of 1:1, 1:2, 1:3 and 1:4 of cholesterol to surfactant respectively to prepare niosomes. Chitosan (CS) coated vesicles were prepared by mixing optimum niosomal formula with CS solution (0.6%). Physicochemical and stability parameters and confocal laser scanning microscopy (CLSM) of developed vesicles were determined. Also, the brain targeting properties of the optimized formula were measured in rats. Niosomes had Entrapment efficiency (EE %) more than 90% and particle size (PS) ranging from 201.3 ± 2.4 nm to 1446 ± 9 nm. TEM photomicrographs of developed vesicles showed a clear shell surrounding the coated vesicles. The produced vesicles exhibited 2.46 folds increase in the amount of drug that permeated nasal mucosa and prolonged OL release compared to drug solution. Coated niosomes further improved drug permeation. CLSM of coated optimum formula showed high permeation across the nasal mucosa. Stability studies revealed non-significant changes in the physicochemical parameters of optimum formula over the storage period. The optimized nasal CS coated niosomes showed a three folds increase in OL concentration in the brain compared to the intranasal solution of the drug. In conclusion, the developed vesicles were efficient in nasal delivery of OL into the brain.

Background: The present study describes glycerosomes (vesicles composed of phospholipids, glycerol and water) as a novel drug delivery system for topical application of celecoxib (CLX) and cupferron (CUP) compound. Aim: The goal of this research was to design topical soft innovative vesicles loaded with CLX or CUP for enhancing the efficacy and avoiding systemic toxicity of CLX and CUP. Methods: CLX and CUP loaded glycerosomes were prepared by hydrating phospholipid-cholesterol films with glycerol aqueous solutions (20–40%, v/v). Box–Behnken design, using Design-Expert® software, was the optimum choice to statistically optimize formulation variables. Three independent variables were evaluated: phospholipid concentration (X₁), glycerol percent (X₂) and tween 80 concentration (X₃). The glycerosomes particle size (Y₁), encapsulation efficiency percent (Y₂: EE %) and drug release (Y₃) were selected as dependent variables. The anti-inflammatory effect of CLX and CUP glycerosomal gel was evaluated by carrageenan-induced rat paw edema method followed by histopathological studies. Results: The optimized formulations (CLX2* and CUP1*) showed spherical morphology under transmission electron microscopy, optimum particle size of 195.4 ± 3.67 nm, 301.2 ± 1.75 nm, high EE of 89.66 ± 1.73%, 93.56 ± 2.87%, high drug release of 47.08 ± 3.37%, 37.60 ± 1.89% and high cumulative amount of drug permeated in 8 h of 900.18 ± 50.24, 527.99 ± 34.90 µg.cm⁻² through hairless rat skin, respectively. They also achieved significant remarkable paw edema inhibition in comparison with the control group (p < .05). Conclusion: Finally, the administration of CLX2* and CUP1* loaded glycerosomal gel onto the skin resulted in marked reduction of edema, congestive capillary and inflammatory cells and this approach may be of value in the treatment of different inflammatory disorders.

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.