What is the fate of multi-lamellar liposomes of controlled size, charge and elasticity in artificial and animal skin?

Multi-lamellar liposomes (MLLs), prepared by shearing a lamellar phase composed of lipids (phosphatidylcholine) and surfactant (Tween 80®), were designed to control their size, charge and elasticity, the key parameters known to influence liposomes penetration through skin. Their size was tuned by the water content of the sheared lamellar phase, and by the surfactant-to-lipid ratio as was their elasticity. Their charge was varied by the incorporation of DPPG and DOTAP to confer a high negative or positive zeta potential, respectively. Couples of MLLs differing solely in one physicochemical parameter, the others kept constant, were compared to discriminate the influence of the key parameters on their penetration through a synthetic membrane, Strat-M™. Using confocal Raman microscopy, the kinetics of MLLs penetration was established for 40 h using a Franz cell dispositive under non-occlusive conditions. From these comparisons, we showed that their transversal diffusion cannot be predicted by one sole parameter but depends on a combination of their physicochemical characteristics that were enlightened. Two types of liposomes designed for topic and systemic diffusion and tested on dog-excised skin exhibited the predicted behavior. Eventually, a mechanism supported by complementary TEM analysis is proposed to shed light on MLLs skin penetration.

Influence of Implants Composition on Melatonin Release from Ethylcellulose Matrix.

BACKGROUND: Melatonin release from Ethylcellulose matrix has never been studied on the whole range of compositions. OBJECTIVE: To perform a comprehensive study about the influence of the melatonin loading on its release from solid ethylcellulose implants, from both a kinetic and structural point of view. METHOD: Cylindrical implants differing in their Melatonin:Ethylcellulose ratio were fabricated to cover a large range of compositions. Drug release was assayed by in vitro dissolution tests in CTAB micellar solutions. The 2D imaging of implant chemical composition during Melatonin release was performed by confocal Raman spectroscopy. FT-IR spectroscopy and Karl-Fisher technique were employed to study implants hydration. RESULTS: A drug radial leakage, whatever the implant composition, is imaged. The apparent diffusion coefficient, D of melatonin was evaluated considering Fickian radial diffusion: its value ranges from 2 to 6 10-12 cm2/s depending on the EC content. The variation of the characteristic drug delivery time with composition was non-monotonous and two different regimes were identified. CONCLUSION: A micellar transport of Melatonin was found. The two regimes in drug release were interpreted considering the polymer barrier effect, the initial porosity and M domains connectivity.