فرمولاسیون و ارزیابی نانوذرات لیپیدی جامد کافئین برای دارورسانی پوستی

Abstract

The purpose of this study was to preparecaffeine-loaded Solid lipid nanoparticles (SLN) formulation with skin targeting for treatment of cellulite. Cellulite is dened as a localized metabolic disorder of subcutaneous tissue that provokes an alteration in the female bodyshape. Among the innumerous possibilities to attenuate the cellulite condition, the use of topical products presents easy access, and the cosmetic approach can be conducted by the consumer. Xanthines, like caffeine, are used in anticellulite cosmetics due to their lipolytic activity on fatty cells via inhibition of phosphodiesterase, stimulating -adrenergic receptors and increasing cyclic adenosine monophosphate (AMP) levels.The principal problem of topical products of caffeine is difculties in being absorbed through the skin. SLNs have attracted increasing attention during recent years. It has been claimed that SLN combine the advantages and avoid the disadvantages of other colloidal carriers.Proposed advantages include possibility of controlled drug, release and drug targeting, increased drug stability, high drug payload,incorporation of lipophilic and hydrophilic drugs feasible,no biotoxicity of the carrier, avoidance of organic solvents,no problems with respect to large scale production and sterilization andhigh percutaneous absorption and drug accumulation in skin.Materials and methods Precirol ATO -5 was selected as the lipid of SLN, Poloxamer 407 and Span 20 were used as the surfactants to stabilize SLN. The hot homogenization method was performed to prepare the drug-loaded SLN. The percutaneous absorption of caffeine in SLN and hydrogel formulations were evaluated in vitro using Franz diffusion cells.The in vivo study was performed by applied topically of hydrogel and Caffeine-SLN gel for 7 and 21 days on female rats. The study regarded thehistological aspects by determination of lysis of fatty cells with a lightmicroscope. DSC and XRD studieswere performed to characterize the model ofdrug incorporation into SLN and lipid crystallinity. The formulation stability was assessed during 12 months in the point of size, size distribution and drug encapsulation. ResultThe mean entrapment efficiency and loading efficiencywere 86.23% and 28.74%, respectively.Thein vitro permeation data showed that Caffeine-loaded SLN formulation can avoid the systemic uptake. The caffeine was 1.4 times more in receptor phase than SLN formulation.Caffeine-SLN gel produced significantly higher deposition of Caffeine in skin (12.1%) than hydrogel (0.75%). Caffeine-SLN showed a good stability during the period of 12 months. No significant change of clarity and phase separation was observed. The good stability might derive from theslow transition of lipid in SLN, low particles size and the stericeffect of Poloxamer 407. The in vivo studies shows the completely lysis of adipocytes by utilize caffeine-SLN gel in comparison with no effect of caffeine-hydrogel.ConclusionPrecirol based SLN dispersions containing caffeine have low particle size and long-term physical stability. The results indicate that the preparedcaffeine-loaded SLN has a promising approach for topical treatment of cellulite.The results of DSC and XRD showed that caffeine was dispersed in SLN in an amorphous state. Lipid content and surfactant play an important role in drug entrapment and particle size. WithSLN formulation, a greater quantityof drug remained localized in the skin with lesser amountpenetrating into the receptor compartment in vitro ascompared with conventional gel, thus enabling drug targetingto skin.