Optimization of topical curcumin spanlastics for melanoma treatment.

The aim of the study was to enhance curcumin skin permeability through the preparation of spanlastics. Spanlastics were prepared using the ethanol injection technique through a central composite design using Span 60 concentration (X1), edge activator type (X2), and its concentration (X3) as the independent variables. The spanlastics were characterized for particle size (PS), encapsulation efficiency (EE), and dissolution efficiency (%DE24h). Formulae with the highest desirability (FN1 and FN2) were prepared and further characterized. They were elastic, spherical, nonirritant, and compatible with the used excipients. They had particle sizes of 147 and 198 nm, encapsulation efficiencies of 84.00% and 89.63%, zeta potential values of -45.50 and -39.10 mV, permeation enhancement ratios of 11.51 and 8.34 folds, and amounts retained of 7.25 and 10.44 µg/cm2 after 24 h, respectively. Formulae FN1 and FN2 showed cytotoxic effects after 48 h on human melanoma A375 with IC50 of 10.9 and 75.6 µg/mL, respectively. They increased the apoptotic effect confirming the success of the spanlastics to be a potential delivery for melanoma treatment.

Application of mathematical modelling to alginate chitosan polyelectrolyte complexes for the prediction of system behavior with Venlafaxine HCl as a model charged drug.

Purpose: This work aimed to develop and analyze the performance of chitosan/alginate polyelectrolyte complex (PEC). Multiple regression and Lab fit curve fitting were applied to derive empirical models for the prediction of zeta potential of plain systems as a function of alginate chitosan ratio. Venlafaxine-HCl was loaded as a model charged drug and empirical models for prediction of its release as a function of time were also derived. Methods: Coacervation method was used for the preparation of green PECs. Preliminary studies were conducted to optimize the preparation method. Pre-adjustment of the pH of alginate and chitosan sols enabled the formation of PECs at alginate/chitosan ratios starting from 1:9 to 9:1. On mixing of alginate and chitosan sols, equal volume dilution method produced spherical particles, while direct mixing method gave fibrous particles. Twenty-seven PECs nanoparticle formulae were prepared using nine alginate/chitosan ratios and three levels of total polymer concentrations. Results: Statistical analysis showed that Zeta potential of the nanoparticle was significantly dependent on alginate/chitosan ratio, while particle size was a function of total polymer concentration. Nine fiber formulae were prepared and evaluated for their appearance and zeta potential. Venlafaxine-HCl release followed anomalous transport mechanism. FT-IR and DSC studies confirmed complexation at the carboxylate and amine site at alginate and chitosan respectively. Conclusion: Chitosan/alginate PECs were successfully obtained without a cross-linker and empirical equations were obtained to help finding the best composition for loading charged drugs and to predict their release profiles.

Formulation of Convenient, Easily Scalable, and Efficient Granisetron HCl Intranasal Droppable Gels.

Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously and orally at the same dose. The prepared formulas gelled instantaneously in simulated nasal fluid and the obtained gels sustained their shear thinning and thixotropic behavior up to 48 h. Polymer type and concentration had significant effects on the apparent viscosities and the in vitro release profile of granisetron from the prepared gels. The drug release data best fitted a modified Higuchi equation with initial burst and followed Fickian diffusion mechanism. A 0.5% gellan-gum-based formula sustained the in vitro drug release up to 3 h and enhanced the drug permeation without need for an enhancer. The histopatholgical study revealed the safety of the tested formula. Intranasal delivery recorded double the drug bioavailabilty in comparison to the oral route. It had an absolute bioavailability of 0.6539 and the maximum plasma drug concentration reached after 1.5 h. The developed formula could be promising for the management of chemotherapy-induced nausea and vomiting regarding its improved bioavailability, patient acceptability, and ease of production.