Rheological and physicochemical characterization of alpha-tocopherol loaded lipid nanoparticles in thermoresponsive gel for topical application

Abstract

Features of a thermoresponsive gel is advantageous in topical application. Lipid nanoparticles is incorporated as a carrier for hydrophobic active ingredient which is not stable in the aqueous gel system. In this work, a thermoresponsive gel mixture consists of carboxymethyl cellulose (CMC) and iota-carrageenan (ι-C) was prepared. Nanostructured lipid carriers (NLC) made of fatty acids and lecithin was incorporated into the gel formulation as a carrier for alpha-tocopherol. Temperature effect on rheological behavior of the prepared gel mixture was investigated. The NLC was evaluated for its mean particle size, zeta potential, morphology, encapsulation efficiency and in vitro drug release. Physicochemical characterization showed that alpha-tocopherol loaded NLC being stored at 4 ˚C was stable for 1 month and encapsulation efficiency of alpha-tocopherol was more than 90 % for all formulations due to its hydrophobicity to stay in the lipid matrix. In vitro release studies proved that NLC was able to provide slow release of loaded alpha-tocopherol. On the other hand, the phase transition from gel-like to liquid-like of the formulated gel mixture was proven to be activated by temperature changes. The rheological gelling point of the gel mixture was represented by the crossover point of storage modulus, G’ and loss modulus, G’’ which was obtained in the vicinity of body temperature 37 ˚C. This property is useful in topical application for its better spreadability on skin upon usage and hence better penetration for the alpha-tocopherol loaded NLC across skin barrier. Prolong release of alpha-tocopherol with enhanced stability is favored as alpha-tocopherol is commonly known for its potent antioxidant activities. These results suggested that gel mixture of CMC and ι-C is a good candidate to be developed as a thermoresponsive gel while lipid nanoparticles is a promising carrier system for alpha-tocopherol in topical use.