Nano Milk Protein-Mucilage Complexes: Characterization and Anticancer Effect.

The anticancer activity of natural compounds has recently attracted multidisciplinary research. In this study, the complexation of milk proteins (MP) with Isabgol husk mucilage (IHM) and Ziziphus spina-christi mucilage (NabM) was investigated. In this context, the physicochemical properties of milk protein mucilage complexes (MPMC) including pH, Carr's index, water solubility, and water absorption indices were measured, and the flow behavior was studied. In addition, the amino acid profile, protein digestibility, and phenolic and flavonoids content of MPMC were explored, and the microstructure of the complexes was visualized using transmission electron microscopy. The antioxidant and anticancer potencies of MPMC against two cancerous cell lines, human liver cancer HEPG-2 and breast cancer MCF-7, in comparison with two normal cell lines, namely, Bj-1 and MCF-12F, were tested using neutral red uptake assay. The results revealed that MPMC had scavenging activity against DPPH, ABTS, and HS radicals. Moreover, MPMC has the potential to prevent DNA damage induced by oxidative stress in Type-Fenton's reaction. The results of the neutral red assay showed significant growth inhibition of both HEPG-2, MCF-7, whereas no significant cytotoxic effect was detected against Bj-1 and MCF-12F. RT-qPCR results indicated MPMC stimulated apoptosis as revealed by the upregulation of the pro-apoptosis gene markers Casepase-3, p53, Bax. Meanwhile, the anti-apoptosis Bcl-2 gene was downregulated. However, no significant difference was observed in normal cell lines treated with MPMC. In conclusion, MPMC can be considered as a promising anticancer entity that can be used in the development of novel cancer therapeutics with comparable activity and minimal side effects compared to conventional cancer chemotherapies.

Scalable flibanserin nanocrystal-based novel sublingual platform for female hypoactive sexual desire disorder: engineering, optimization adopting the desirability function approach and in vivo pharmacokinetic study.

Flibanserin (FLB) was approved by FDA for the treatment of pre-menopausal female hypoactive sexual desire disorder (HSDD). FLB suffers from low oral bioavailability (33%) which might be due to hepatic first-pass metabolism in addition to its poor aqueous solubility. The sublingual route could be a promising alternative for FLB due to the avoidance of enterohepatic circulation. However, the drug needs to dissolve in the small volume of saliva in order to be absorbed through the sublingual mucosa. Therefore, FLB nanocrystals were prepared by sono-precipitation technique according to 23 full factorial design. FLB-nanocrystals were formulated using two surfactants (PVP K30 and PL F127) in two different amounts (200 and 400 mg) and the volume of ethanol was either 3 or 5 mL. Nanocrystal formulation was optimized according to the desirability function to have a minimum particle size, zeta potential, polydispersity index, and maximum saturated solubility. The optimized formula had a particle size of 443.12 ± 14.91 nm and a saturated solubility of 23.27 ± 4.62 mg/L which is five times the saturated solubility of FLB. Nanocrystal dispersion of the optimized formula was solidified by freeze-drying and used to prepare rapidly disintegrating sublingual tablets containing Pharmaburst® as superdisintegrant. Sublingual tablet formulation with the shortest disintegration time (36 s) was selected for the in vivo study. FLB nanocrystal-based sublingual tablets exhibited a two-fold increase in bioavailability with a faster onset of action compared to the commercially available oral formulation. These findings prove the potential application of FLB nanocrystal-based sublingual tablets in the treatment of HSDD.

Microenvironmental pH-modified Amisulpride-Labrasol matrix tablets: development, optimization and in vivo pharmacokinetic study.

Amisulpride (AMS) is atypical antipsychotic with a weak basic nature (pKa 9.37), which results in low solubility in the high pH of the intestine. It is also recognized as a substrate of P-glycoprotein efflux pump. Both factors lead to its low oral bioavailability (48%). The daily dose of AMS is between 200 and 1200 mg to be taken in divided doses which compromise patient compliance. Therefore, controlled release formulation of AMS is of clinical significance. AMS was formulated into matrix tablets containing Labrasol, P-glycoprotein efflux inhibitor, and a penetration enhancer, using direct compression technique. The tablets were prepared according to 21·41 factorial design using two polymers, namely, HPMC and Carbopol 934 at four concentrations (20%, 30%, 40%, 50%). Percentage AMS released after 2 h (Q2hr%) and 8 h (Q8hr%) were chosen as dependent variables. Two acidic pH modifiers (fumaric acid and tartaric acid) at two levels (15% and 30%) were incorporated in the tablet according to 22 factorial design. All formulae with acidic pH modifier had similarity factor (f2) ≥ 50 proving the pH independent release of AMS. The pharmacokinetic study in rabbits revealed 30% enhancement of the oral absorption AMS imparted by the pH-modified matrix tablet containing Labrasol. Graphical abstract.

Correction to: Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study.

The second author's name was incorrectly published as "Niha F. Younes". The correct name is "Nihal Farid Younes" as shown above in the list of authors.

Enhanced Oral Absorption of Amisulpride Via a Nanostructured Lipid Carrier-Based Capsules: Development, Optimization Applying the Desirability Function Approach and In Vivo Pharmacokinetic Study.

Amisulpride (AMS), a second generation antipsychotic, suffers from low oral bioavailability (48%). This might be due to its pH-dependent solubility or being a substrate of P-glycoprotein efflux pump. Nanostructured lipid carriers (NLCs) were proposed in this study to enhance the oral absorption of AMS. AMS-NLCs were prepared by solvent evaporation technique according to (21.41.31) factorial design, whereas the type of solid lipid (tripalmitin or Gelucire® 43/1), lipid to drug ratio (7:1, 10:1, or 13:1) and type of external suspending medium (double distilled water, 0.5% TSP pH 12, 1% HPMC or 2.5% glycerin) were the independent variables. The average entrapment efficiency, particle size, polydispersity index, and zeta potential of the prepared formulations ranged from 29.01 to 69.06%, 184.9 to 708.75 nm, 0.21 to 0.59, and - 21 to - 33.55 mV, respectively. AMS-NLCs were optimized according to the desirability function to maximize the entrapment efficiency and minimize the particle size. Formulae G12, G10, and G7 with the highest desirability values of 0.915, 0.84, and 0.768, respectively, were chosen for further investigations. Novel AMS-NLCs capsules were prepared from the lyophilized formulations (TG7 and MG10) to enhance stability and increase patient compliance. The capsules were evaluated in terms of weight variation, content uniformity, and in vitro release pattern. The pharmacokinetics of AMS-NLCs capsules (formula TG7) were tested in rabbits compared to the commercial Amipride® tablets. The relative bioavailability of AMS-NLCs capsules was found to be 252.78%. In conclusion, the NLC-based capsules show potential to improve the oral bioavailability of AMS.

Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats.

Traditional azole antifungal formulations suffer from poor retention in the vaginal cavity, irritation and burning of the vaginal area. In the present work, we aim at the development of a novel miconazole (MCZ) microsponges gel as an attractive dosage form for vaginal candidiasis. The proposed formula has the potential to minimize the local side effects of the drug due to the controlled release characteristic, which increases patient compliance. Moreover, the mucosal retention effect of the microsponges in addition to the bioadhesion property of Carbopol gel prolongs the retention of the dosage form in the vagina and consequently improves the therapeutic efficiency. MCZ microsponges were prepared applying Quasi emulsion method using Eudragit RS100. The effect of formulation factors, namely, drug:polymer ratio (1:1, 2:1 and 4:1), the amount of poly vinyl alcohol (PVA) (25, 50 and 75mg) and the volume of organic solvent (2.5, 5, 10mL) on the characteristics of MCZ microsponges has been investigated. The microsponges were optimized regarding the production yield (68.8±6.4%), particle size (78.2±2.1µm), entrapment efficiency (92.9±1.9%) and release rate (Q150 51.8±2.5%). The selected formula was further evaluated for its, flowability, porosity and surface morphology. MCZ microsponges were incorporated into Carbopol gel, then the viscosity and bioadhesion were examined. The in vitro antifungal activity of MCZ microsponges gel was comparable to the market product. In vivo, MCZ microsponges vaginal gel was more effective than the market product (p<0.05) in eradicating Candida infection in rats, which was supported by the histopathological findings.