The formulation and in vitro evaluation of WS Biotin, a novel encapsulated form of D-Biotin with improved water solubility for hair and skin treatment applications.

OBJECTIVE: To develop and evaluate the efficacy of WS Biotin, a novel water-soluble form of D-Biotin, for cosmetic use. METHODS: A new encapsulated form of D-Biotin was developed with the purpose of improving the water solubility of biotin. This novel form of encapsulated biotin was characterized by its physicochemical properties: particle size, D-Biotin content and solubility in water. Also, proliferation and gene expression in vitro tests in cell culture were performed to evaluate its effectiveness in promoting hair growth, an ELISA test was conducted for hair keratinization and skin lightening property was tested by analysing the intracellular melanin content. RESULTS: The developed WS Biotin microcapsules exhibit a particle size range of 2-30 µm with D-Biotin content of ~50% (w/w). The water solubility of WS Biotin was found to be 20-fold greater than free biotin. The obtained in vitro results indicated that WS Biotin enhances the expression of hair-related keratins in hair follicle keratinocytes, as well as the expression of hair growth-promoting genes in dermal papilla cells. Moreover, the melanin content in UVA-exposed epidermal melanocytes was reduced upon exposure to WS Biotin. CONCLUSION: In this work, a novel form of encapsulated biotin, WS Biotin, was developed in order to improve the water solubility of free biotin and was found to be effective for cosmetic use in both hair and skin applications.

OBJECTIF: Développer et évaluer l'efficacité de la WS Biotin, une nouvelle forme hydrosoluble de D-biotine, à usage cosmétique. MÉTHODES: Une nouveau format gélules de D-biotine a été développé dans le but d'améliorer la propriété d'hydrosolubilité de la biotine. Ce nouveau format de gélules de biotine a été caractérisé pour ses propriétés physicochimiques : taille des particules, teneur en D-biotine et solubilité dans l'eau. En outre, des tests in vitro de prolifération et d'expression génique en culture cellulaire ont été réalisés pour évaluer son efficacité à favoriser la croissance des cheveux, un test ELISA a été réalisé pour la kératinisation des cheveux et la propriété d'éclaircissement de la peau a été testée en analysant la teneur en mélanine intracellulaire. RÉSULTATS: Les microgélules de WS Biotin développées présentent une plage de tailles de particules de 2 à 30 micromètres avec une teneur en biotine D d'environ 50 % (p/p). L'hydrosolubilité de WS Biotin s'est avérée 20 fois plus élevée que celle de la biotine libre. Les résultats in vitro obtenus ont indiqué que WS Biotin améliorait l'expression des kératines capillaires dans les kératinocytes des follicules pileux, ainsi que l'expression des gènes favorisant la croissance dans les cellules papillaires dermiques. En outre, la teneur en mélanine dans les mélanocytes épidermiques exposés aux UVA a été réduite lors de l'exposition à WS Biotin. CONCLUSION: Dans ce travail, une nouvelle forme de biotine en gélule, WS Biotin, a été développée afin d'améliorer l'hydrosolubilité de la biotine libre et s'est avérée efficace pour une utilisation cosmétique dans les applications capillaires et cutanées.

Anti-HER2 cationic immunoemulsion as a potential targeted drug delivery system for the treatment of prostate cancer.

Present management of metastatic prostate cancer, which includes hormonal therapy, chemotherapy, and radiotherapy, are frequently palliative. Taxanes, and specifically docetaxel, are being extensively investigated to improve the survival of metastatic prostate cancer patients. Although paclitaxel exhibits a wide spectrum of antitumor activity, its therapeutic application is limited, in part, due to its low water solubility that necessitates the use of Cremophor EL, which is known to induce hypersensitivity reactions. Therefore, the objective of this present study was to assess the efficiency of paclitaxel palmitate-loaded anti-HER2 immunoemulsions, a targeted drug delivery system based on cationic emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a well-established in vivo pharmacologic model of metastatic prostate cancer that overexpresses the HER2 receptor. It was clearly noted that the cationic emulsion and immunoemulsion did not activate the complement compared with the commercial and paclitaxel palmitate hydroalcoholic formulations. In addition, 10 mg/kg of paclitaxel palmitate-loaded immunoemulsion once weekly over 3 weeks inhibits the tumor growth in severe combined immunodeficient mice much more than the cationic emulsion (P < 0.05) and the paclitaxel palmitate formulation (P < 0.01). The histopathologic analysis suggested a therapeutic improvement trend in favor of the immunoemulsion. However, there was no significant difference in antimetastatic activity between the emulsion and the immunoemulsion despite the affinity of the immunoemulsion towards the HER2 receptor. Although the tumor growth was not fully inhibited, the actual results are encouraging and may lead to an improved therapeutic strategy of metastatic prostate cancer treatment.

The design and evaluation of a novel targeted drug delivery system using cationic emulsion-antibody conjugates.

In an attempt to design a targeted drug delivery system to tumors' over-expressing H-ferritin specifically recognized by a monoclonal antibody, AMB8LK, a cationic emulsion - AMB8LK conjugate was prepared. A novel cross-linker molecule bearing maleimide group was synthesized and added to cationic emulsion formulation for AMB8LK Fab' fragment covalent coupling. NMR spectroscopy confirmed the cross-linker synthesis and the preservation of the active maleimide function. SDS gel-electrophoresis results corroborated the formation of the Fab' fragment. Different densities of Fab' fragments (10-200 Fab'/oil droplet) were conjugated to emulsion droplet interface and no changes in the physico-chemical properties were observed ( approximately 120 nm size and zeta potential of approximately +30 mV). The coupling efficiency ranged from 55% to 70% and was visualized by TEM showing gold particles attached to the droplet interface. Cell culture studies demonstrated specific binding to cells as confirmed by the occurrence of the marked reduction in binding when free AMB8LK Mab was incubated before adding the AMB8LK-emulsion conjugate to the cells. The coupling of AMB8LK Fab' fragment to the cationic emulsion increased the cells uptake by 50% as compared to non-conjugated respective cationic emulsion. Appropriate conditions were, thus, identified for coupling AMB8LK Fab' fragment to cationic emulsion without altering the specificity and affinity of the Mab fragment to the tumor antigen.

Extensive surface studies help to analyse zeta potential data: the case of cationic emulsions.

The present study is aimed to characterize the electrostatic parameters of oil in water emulsion droplets composed of MCT (medium chain triglycerides), PL (phospholipids) and Poloxamer and containing increasing concentrations of the cationic lipid oleylamine (OA), in Hepes 20 mM pH 7.4. The initial zeta-potential data suggesting saturation of the droplet surface at high OA concentrations were completed by supplementary analysis: the distribution of the oleylamine within the droplet was determined by reacting the amino groups with the hydrophilic TNBS (trinitrobenzenesulfonic acid), the method being initially standardised with vesicles. In addition, surface potential and pH at the droplet surface were monitored by the pH-sensitive fluorophore 4-heptadecyl-7-hydroxycoumarin. Our results demonstrate that almost all the OA is localised and fully ionised at the droplet surface for all concentrations and that the observed plateau in the zeta-potential values obeys the Gouy-Chapman theory of ion condensation. It is also shown that the slipping plane separation as estimated by the Eversole-Boardman equation is higher that the expected values of 0.2 nm as a result of the relative position of the fluorophore and the outer boundary of the lipid interface thickness and the Poloxamer anchored at the interface only plays a minor role.