Elastic cationic liposomes for vitamin C delivery: Development, characterization and skin absorption study.

The influence of hydrophilic surfactants acting on the membrane elasticity of liposomes on the skin absorption of vitamin C is investigated. The purpose of encapsulation inside cationic liposomes is to improve the skin delivery of vitamin C. The properties of elastic liposomes (ELs) are compared to that of conventional liposomes (CLs). ELs are formed by the addition of the "edge activator" Polysorbate 80 to the CLs composed of soybean lecithin, cationic lipid DOTAP (1,2-dioleoyl-3-trimethylammoniopropane chloride), and cholesterol. The liposomes are characterized by dynamic light scattering and electron microscopy. No toxicity is detected in human keratinocyte cells. Evidences of Polysorbate 80 incorporation into liposome bilayers and of the higher flexibility of ELs are given by isothermal titration calorimetry and pore edge tension measurements in giant unilamellar vesicles. The presence of a positive charge in the liposomal membrane increases the encapsulation efficacy by approximately 30% for both CLs and ELs. Skin absorption of vitamin C from CLs, ELs and a control aqueous solution measured in Franz cells shows a high delivery of vitamin C into each skin layer and the acceptor fluid from both liposome types. These results suggest that another mechanism drives skin diffusion, involving interactions between cationic lipids and vitamin C depending on the skin pH.

Supercritical carbon dioxide solubility measurement and modelling for effective size reduction of nifedipine particles for transdermal application.

Nifedipine (NIF) is a Class II drug of the Biopharmaceutical Classification System (BCS) with low oral bioavailability, low dissolution rate and significant hepatic drug metabolism. The transdermal route using supersaturated systems could be considered. For this purpose, physicochemical properties of NIF such as its dissolution rate, may be a limiting factor and must be improved. Crystallization processes assisted by supercritical carbon dioxide (scCO2) and particularly the Rapid Expansion of Supercritical Solution (RESS) process may improve drug bioavailability by reducing particle size and consequently increasing surface area. This study addresses the reduction of NIF particle size using scCO2-RESS as crystallization process. Experimental solubility studies were performed at different temperature (308 and 318 K) and pressure ranges (9-24 MPa). Solubility data were correlated with two thermodynamic models in order to predict NIF solubility in scCO2. Optimized operating conditions, identified by thermodynamic modelling, allowed the production of thinner NIF particles and a size reduction up to ten fold. Particle size reduction improved NIF dissolution kinetics in aqueous medium: after 90 min, 42 % of raw NIF was released against 80 % for crystallized NIF. The scCO2-RESS process is a solvent free process, that can produce micronized or nanosized crystals able to improve physicochemical properties of poorly water-soluble drugs.

Stabilization of vitamin C in emulsions of liquid crystalline structures.

Emulsified systems are widely used for topical delivery with the aim of optimizing cutaneous absorption and offering a pleasant sensory. They also may provide a protection of the active molecule against oxidation and/or degradation. The oil phase of o/w emulsions may consist of liquid crystalline structures, especially lamellar structures which are similar to those found in the stratum corneum lipids. In the present work, o/w emulsions containing liquid crystals of mixed cetyl alcohol and Polysorbate 60 were developed for topical delivery of vitamin C, a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. In addition to the well-documented lipid supplementation of the stratum corneum, the liquid crystal emulsions provide a significant chemical stabilization of vitamin C against its degradation. Emulsions were characterized by X-ray diffraction, polarized optical microscopy, and transmission electron microscopy. The stability of vitamin C in the formulations was evaluated upon storage in different conditions of temperature. The emulsions contain a complex colloidal structure, consisting of lamellar liquid crystalline (Lα) and crystalline lamellar gel (Lß) phases, that provide a very efficient protection of vitamin C against its degradation.

Inorganic ions in the skin: Allies or enemies?

Skin constitutes a barrier protecting the organism against physical and chemical factors. Therefore, it is constantly exposed to the xenobiotics, including inorganic ions that are ubiquitous in the environment. Some of them play important roles in homeostasis and regulatory functions of the body, also in the skin, while others can be considered dangerous. Many authors have shown that inorganic ions could penetrate inside the skin and possibly induce local effects. In this review, we give an account of the current knowledge on the effects of skin exposure to inorganic ions. Beneficial effects on skin conditions related to the use of thermal spring waters are discussed together with the application of aluminium in underarm hygiene products and silver salts in treatment of difficult wounds. Finally, the potential consequences of dermal exposure to topical sensitizers and harmful heavy ions including radionuclides are discussed.

Ultrasound assisted crystallization of a new cardioactive prototype using ionic liquid as solvent.

This work deals with the antisolvent crystallization of LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) assisted by ultrasound. An ionic liquid (IL), 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] was used as solvent and water as antisolvent. The influence of the following parameters on crystals properties (size distribution, morphology, residual solvent and in vitro dissolution) were studied with two mixing mode (quick and dropwise) of solution with antisolvent. The impact of washing and drying process was also evaluated. Comparative studies of conventional crystallization conditions (without ultrasound) were also performed. The effect of ultrasound on LASSBio-294 recrystallized properties was influenced by the add mode, water/IL ratio and drug solution concentration. As example, US promoted the formation of small crystals with high residual IL under the following conditions: quick addition, high drug solution concentration and high water/IL ratio. However, despite the decrease of elementary particle size, ultrasound did not avoid crystals agglomeration. The drug dissolution rate was affected by the physical structure of agglomerates. When employed as drying process of washed crystals, spray drying reduced this agglomeration and improved the dissolution of LASSBio-294 crystals.