Skin is considered the most accessible organ of the body because of its underlying capillary network. However, stratum corneum (SC), the upper most layer of skin, represents major diffusional barrier for most drugs. Hence, the use of edge activators (EAs) in designing novel elastic vesicles is hypothesized to impart their lipid bilayer with ultra-flexibility to trespass SC by high self-optimizing deformability. To confirm this hypothesis, this work aimed at developing novel bilosomes by modulating conventional niosomal composition using different bile salts as EAs and investigating their superiority over niosomes for transdermal delivery of diacerein (DCN), as model drug. Bilosomes were prepared by thin film hydration (TFH) technique according to full 3.2 factorial design to select the optimal formulation using Design-Expert software. The optimal bilosomes (B6) showed nanosized vesicles (301.65 ± 17.32 nm) and 100.00 ± 0.00 % entrapment efficiency. Ex vivo permeation studies and in vivo evaluation revealed that B6 exhibited superior permeation and drug retention capacity compared to the conventional niosomal formulation and drug suspension. Furthermore, B6 was subjected to in vivo histopathological study using male Wistar rats which ensured its safety for topical application. Overall, the results confirmed the hypothesized superiority of bilosomes over niosomes for enhancing DCN flux across the skin.

Diacerein (DCN) is a hydrophobic osteoarthritis (OA) drug with short half-life and low oral bioavailability. Furthermore, DCN oral administration is associated with diarrhea which represents obstacle against its oral use. Hence, this article aimed at developing elastosomes (edge activator (EA)-based vesicular nanocarriers) as a novel transdermal system for delivering DCN efficiently and avoiding its oral problems. For achieving this goal, elastosomes were prepared according to 41.21 full factorial design using different EAs in varying amounts. The prepared formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and deformability index (DI). Desirability function was employed using Design-Expert® software to select the optimal elastosomes (E1) which showed EE% of 96.25 ± 2.19%, PS of 506.35 ± 44.61 nm, PDI of 0.46 ± 0.09, ZP of −38.65 ± 0.91 mV, and DI of 12.74 ± 2.63 g. In addition, E1 was compared to DCN-loaded bilosomes and both vesicles exhibited superior skin permeation potential and retention capacity compared to drug suspension. In-vivo histopathological study was performed which ensured the safety of E1 for topical application. Furthermore, the pharmacokinetic study conducted in albino rabbits demonstrated that there was no significant difference in the rate and extent of DCN absorption from topically applied E1 compared to oral suspension. Multiple level C in-vitro in-vivo correlation showed good correlation between in-vitro release and in-vivo drug performance for E1 and DCN oral suspension. Overall, results confirmed the admirable potential of E1 to be utilized as novel carrier for transdermal delivery of DCN and bypassing its oral side effects.

Results revealed that a transdermal niosomal system was successfully prepared and evaluated using central composite design which will result in delivering diacerein efficiently, avoiding its oral problems.

Fungal keratitis (FK) is a devastating ocular disease that can cause corneal opacity and blindness if not treated effectively. Tolnaftate (TOL) is a selective fungicidal drug against Aspergillus spp. which are among the most common causes of mycotic keratitis. TOL is lipophilic drug with low water solubility and permeation which act as obstacles for its clinical ocular efficacy. Hence, this study aimed to statistically optimize a novel polymeric pseudorotaxanes (PSRs) containing TOL for enhancing its ocular permeability and antifungal effect. For achieving this goal, a full 3 1 .2 2 factorial design was fashioned for preparing and optimizing TOL-PSRs using film hydration technique. Three formulation variables were studied: drug amount (X 1 ), weight ratio of Pluronics to HPβCD (X 2 ) and Pluronic system (X 3 ). Entrapment efficiency percent (EE%) (Y 1 ), particle size (PS) (Y 2 ) and zeta potential (ZP) (Y 3 ) were set as dependent variables. The selected optimal TOL-PSRs (PSR1) showed EE% of 71.55 ± 2.90%, PS of 237.05 ± 12.80 nm and ZP of −32.65 ± 0.92 mV. In addition, PSR1 was compared to conventional polymeric mixed micelles (PMMs) and both carriers significantly increased the drug flux and resulted in higher amount permeated per unit area in 8 h compared to drug suspension. The histopathological studies assured the safety of PSR1 for ocular use. The in vivo susceptibility testing using Aspergillus niger confirmed that PSR1 displayed sustained antifungal activity up to 24 h. The obtained results revealed the admirable potential of PSR1 to be used as novel nanocarriers for promoting TOL ocular delivery.

Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 32 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 31.21 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery.

Background: Many people nowadays are suffering from mental or behavioral disorders. The Egyptian community is complaining from an increase in the appearance of mental disorders with a lot of treatment options. Increasing prevalence of psychiatric disorders is not limited to adults, but also appears in children and adolescents. The treatment of psychiatric disorders as schizophrenia, depression, bipolar disorder and autism usually involve the long-term taking of antipsychotic drugs. Therefore, the uses of antipsychotics have increased. Two main drugs are used quetiapine and aripiprazole. Aripiprazole has been used with satisfactory results. It is known to-act on the dopaminergic receptors which have been detected in the germinal cells. Aim of work: To detect the histological changes induced by aripiprazole on the structure of the seminiferous tubules of albino rats and the possible recovery of the tubules after drug withdrawal. Material and Methods: Twenty four prepubertal male albino rats were used in this study aged two weeks and weighed forty grams. The rats were divided into the following groups: Group (I): Control group: included twelve rats. Six rats were left without any medication throughout the experiment (group IA). The other six rats received 0.2 ml of 0.9% NaCl via oral gavage daily for 45 days (group IB). Group (II): Aripiprazole group: included twelve rats which received aripiprazole at a dose of 2 mg/kg B.W/day dissolved in 5 ml of 0.9% NaCl taken via oral gavage for 45 days. After this period (immediately after stoppage of drug administration), six of the rats in the group were sacrificed (group IIA). The other six were sacrificed after another 45 days (they were left without taking any drugs and considered group IIB i.e. a withdrawal period). After scarification, dissection of the testes was done. Specimens from both testes of all groups were taken and processed for light microscopic study. Results: The testes of all groups showed that the seminiferous tubules lost their normal architecture pattern. Multiple vacuolations replaced the cellular elements. Focal depletions or generalized cellular loss occurred. The lumen was empty in most of the tubules. Irregularity of the basement membrane of the tubules was a common finding as well as congestion of the blood vessels and exudation in between the tubules. The withdrawal group of aripiprazole still showed damage of the seminiferous tubules. Conclusion: The adverse effect of aripiprazole on the seminiferous tubules was evident and there was no significant improvement after withdrawal of the drug.