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.

Objective: One of the greatest challenges drug formulation is facing is poor bioavailability via oral route. In this regard, nasal drug delivery has been commonly used as an alternative route to improve drug bioavailability. Nefopam hydrochloride (NF) is an analgesic drug that suffers from poor bioavailability due to extensive metabolism in liver. Accordingly, the goal of the present study was to improve NF bioavailability via niosomal-based formulation designed for intranasal delivery. Materials and methods: Vesicles were developed by mixing surfactants (Span 20, Span 40, Span 80, and Span 85) at four molar ratios of 1:1, 1:2, 1:3, and 1:4 of cholesterol to surfactant. Entrapment efficiency, particle size, zeta potential, release percentage, ex-vivo permeation parameters, and niosomes’ stability were determined. Also, the pharmacokinetic parameters of the optimized formula in in-situ gel base were measured in rats. Results: Niosomes showed entrapment efficiency >80%, particle size <550 nm, and zeta potential ranging from -16.8±0.13 to -29.7±0.15. The produced vesicles showed significantly higher amounts of drug permeated across nasal mucosa (2.5 folds) and prolonged NF release compared with NF solution. Stability studies of optimum formula showed nonsignificant changes in niosomes parameters over a storage period of 6 months. The in-vivo studies showed a 4.77-fold increase in bioavailability of optimized nasal niosomes compared with oral solution of drug. Conclusion: The obtained results revealed the great ability of the produced NF-loaded niosomes to enhance drug penetration through nasal mucosa and improve its relative bioavailability compared with NF oral solution.

Chronic wounds are a serious problem that could cause severe morbidity and even death. The ability of statins including rosuvastatin calcium (RVS) to enhance wound healing was well reported. However, RVS is poorly soluble and has low bioavailability. Thus, this study aimed to prepare and evaluate RVS-loaded nanocubics to enhance its skin performance. In addition, silver nanoparticles (AgNPs) exhibited potent antimicrobial activity, thus, the optimum RVS-loaded nanocubics was capped with AgNPs to evaluate its effect in wound management. Box–Behnken design was adopted to prepare RVS nanocubics. The design investigated the effect of lecithin, poloxamer 407 concentrations and hydration time on vesicle size, zeta potential (ZP), entrapment efficiency (EE%) and in vitro drug release%. Optimum formulation capped with AgNPs was incorporated into a gel base and examined for wound healing efficiency using different pharmacological tests in rats. Nanocubics have shown a mean diameter between 167.2 ± 7.8 and 408 ± 18.4 nm, ZP values ranging from −20.9 ± 1.9 to −53.5 ± 4 mV, EE% equivocated between 31.6 ± 1.4 and 94.4 ± 8.6 and drug release after 12 h between 17.9 ± 1.9 and 68.0 ± 4.0%. The histopathological studies and serum tumour necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels confirmed the greater efficacy of RVS nanocubics capped with AgNPs gel in wound healing when compared with gentamicin ointment. RVS-loaded nanocubic vesicles and AgNPs-loaded hydrogel could be considered as a promising platform to enhance the wound healing and tissue repair processes.

Eradication of ophthalmic infections depends on increasing transcorneal permeation and localizing antibiotics at ocular surface. This study aimed at formulating lomefloxacin HCl (LF) in the form of niosomes and evaluating the in vivo performance of best formula in rabbits’ eyes. Vesicles were developed by mixing three surfactants at three molar ratios of 1:1, 1:2 and 1:3 of surfactant to cholesterol. Size, zeta potential, release percentage, transcorneal permeation parameters, stability studies, cytotoxicity and antibacterial activity of niosomes were determined. Niosomes showed encapsulation efficiency of more than 78%, particle size below 500 nm and zeta potential below −43.6. The produced vesicles showed significantly higher amounts of drug permeated across cornea (166%) compared to LF solution. The in vivo study showed 2–5 folds increase in drug concentration in ocular fluids and tissues following administration of niosomes compared to marketed formula (from 3.75 to 10.31 mcg/mL in the cornea). Microbiological studies showed 35 folds increase in the antibacterial activity of LF niosomes compared to free drug; where MBC decreased from 31.25 mcg/mL in case of LF solution to 0.97 mcg/mL for niosomal gel. The formulated niosomes enhanced the ocular bioavailability of LF through increasing transcorneal permeation and localizing drug at site of action.

Burn wound healing is a complex process that involves the repair of injured tissues and the control of infection to diminish the scar formation, pain, and discomfort associated with such injuries. The aim of this research was to formulate and optimize a self-nanoemulsion drug delivery system based on the use of coconut oil and loaded with simvastatin. Coconut oil possesses antiinflammatory and antibacterial activity, and simvastatin has interesting properties for promoting the wound-healing process because it increases the production of the vascular endothelial growth factor at the site of injury. The Box–Behnken design was employed for the optimization of the coconut oil–simvastatin self-nanoemulsion drug delivery system. The prepared formulations were characterized according to globular size and their activity in the healing of burn wounds by assessing the mean wound diameter and level of interlukin-6 in experimental animals. Additionally, the antimicrobial activity of the prepared formulations was assessed. The nanoemulsion was considered adequately formed when it had droplets of between 65 and 195 nm. The statistical design proved the important synergistic effect of coconut oil and simvastatin for burn wound management in their synergistic potentiation of wound closure and their anti-inflammatory and antimicrobial effects. The optimum formulation achieved up to a 5.3-fold decrease in the mean burn wound diameter, a 4.25-fold decrease in interleukin-6 levels, and a 6-fold increase in the inhibition zone against Staphylococcus aureus when compared with different control formulations. Therefore, the designed nanoemulsions containing a combination of coconut oil and simvastatin could be considered promising platforms for the treatment of chronic and burn wounds.

Duloxetine HCl (DXH) is a reuptake inhibitor of serotonin and norepinephrine used to treat the major depressive disorder. Following its extensive hepatic metabolism, acid-labile nature, and limited aqueous solubility, DXH has poor oral bioavailability (40%). The rectal route has been suggested as another route of administration to surmount such challenges. The present study aimed to prepare DXH-loaded glycerosomal (DXH-GLYS) in situ gel for rectal administration to increase DXH permeability and improve its bioavailability. Box–Behnken design (BBD) was adopted to prepare and optimize nanoglycerosomes. The impact of Phospholipon 90G (PL90G), Tween 80 concentrations, and glycerol percentage on encapsulation efficiency, nanoglycerosomal size, % cumulative DXH released, and the cumulative DXH permeated per unit area after 24 h were studied by the design. The pharmacokinetic and pharmacodynamic behavior of optimized formulation was investigated in rats. The formulated DXH-GLYS had a vesicle size ranging between 135.9 and 430.6 nm and an entrapment efficiency between 69.11 and 98.12%. The permeation experiment revealed that the optimized DXH-GLYS in situ gel increased DXH permeation by 2.62-fold compared to DXH solution. Pharmacokinetics studies disclosed that the DXH-GLYS in situ rectal gel exhibited 2.24-times increment in DXH bioavailability relative to oral DXH solution. The pharmacodynamic study revealed that the DXH-GLYS rectal treatment significantly improved the behavioral analysis parameters and was more efficacious as an antidepressant than the oral DXH solution. Collectively, these findings demonstrate that GLYS can be considered a potentially valuable rectal nanocarrier that could boost the DXH efficacy. Graphical abstract