Development and In Vitro Evaluations of a Lipid Nanoparticle Formulation Containing Tretinoin

Abstract

Tretinoin has shown its effectiveness in the treatment of several skin diseases, such as acne vulgaris, photoaging, psoriasis, and epithelial skin cancer. Nevertheless, formulation of effective delivery systems of tretinoin is challenging due to its poor solubility as well as high chemical- and photo-instability. Furthermore, skin irritation cause by tretinoin upon topical application is also a concern. In addition, sustained and prolonged drug release is required at the disease site for effective treatment. Keeping all these in mind, we hypothesized that encapsulation of tretinoin in solid lipid nanoparticles (SLNs) will avoid the above mentioned drawbacks associated with tretinoin. Additionally, SLNs are expected to penetrate into skin due to its nano size and provide sustained and prolonged drug release due to solid matrix of SLNs. Thus, SLNs containing tretinoin were developed by varying different formulation parameters, such as types of lipids, types of surfactants, lipid concentration, surfactant concentration, drug concentration, homogenization time, and sonication time. Emulsification-ultrasonification method was adopted to prepare SLNs. Particle size, polydispersity index (PI), and zeta potential (ZP) were measured by photon correlation spectroscopy. Surface morphology and shape of SLNs were checked by cryogenic scanning electron microscopy (cryo-SEM). Encapsulation efficiency (EE) of the SLNs was determined by HPLC. Drug release study was performed in 10 mM phosphate buffer containing 2% Tween® 80 (pH 7.4). Further, short-term stability study was also performed to check the stability of SLNs. Formulation parameters exhibited significant impact on the size, PI, ZP, and EE. The developed SLNs demonstrated 113.50±0.89 nm particle size, 0.182±0.007 PI, -38.70±0.56 mV ZP, and 78.18±4.26% EE. Cryo-SEM image revealed smooth and spherical SLNs. SLNs were stable during storage at 4°C. In vitro drug release study showed sustained and prolonged drug release from SLNs. Hence, the developed tretinoin-loaded SLNs can be incorporated into a gel formulation for topical application.