Isotretinoin-loaded solid lipid nanoparticles with skin targeting for topical delivery

Abstract

The purpose of this study was to construct isotretinoin-loaded SLN (IT-SLN) formulation with skin targeting for topical delivery of isotretinoin. PRECIROL ATO 5 was selected as the lipid of SLN. Tween 80 and soybean lecithin were used as the surfactants to stabilize SLN. The hot homogenization method was performed to prepare the drug-loaded SLN. The various formulations were characterized by photon correlation spectroscopy and all the SLN formulations had low average size between 30 and 50 nm. Transmission electron microscopy studies showed that the IT-SLN formulation had a spherical shape. All the formulations had high entrapment efficiency ranging from 80% to 100%. The penetration of isotretinoin from the IT-SLN formulations through skins and into skins were evaluated in vitro using Franz diffusion cells fitted with rat skins. The in vitro permeation data showed that all the IT-SLN formulations can avoid the systemic uptake of isotretinoin in skins, however the control tincture had a permeation rate of 0.76 ± 0.30 μg cm⁻² h⁻¹ through skins. The IT-SLN consisting of 3.0% PRECIROL ATO 5, 4.0% soybean lecithin and 4.5% Tween 80 could significantly increased the accumulative uptake of isotretinoin in skin and showed a significantly enhanced skin targeting effect. The studied IT-SLN showed a good stability. These results indicate that the studied IT-SLN formulation with skin targeting may be a promising carrier for topical delivery of isotretinoin.

Introduction

Isotretinoin, a derivative of retinoic acid (13-cis-retinoic acid), has been commonly used for the treatment of severe acne and the other dermatological diseases (Katsambas and Papakonstantinou, 2004). However, it has obvious adverse side effects by oral administration. The launched topical preparations such as cream also show systemic absorption and significant skin irritation (Queille-Roussel et al., 2001). So, it is necessary to improve the skin uptake and reduce systemic absorption of isotretinoin using a carrier with an ability of skin targeting.

During the past several years, solid lipid nanoparticles (SLN) began to act as a topical carrier not only for pharmaceutical molecules, but also for cosmetic products (Müller et al., 2002). Compared with conventional carriers such as cream, tincture and emulsion, SLN combine their advantages such as controlled release, in vivo good toleration and protection of active compounds (Müller et al., 2000, Sylvia et al., 2003). Especially, SLN can favor drug penetration into the skins (Jenning et al., 2000, Wissing and Müller, 2003), maintain a sustained release to avoid systemic absorption (zur Mühlen et al., 1998), act as a UV sunscreen system (Wissing and Müller, 2002), reduce irritation (Maia et al., 2000, Sivaramakrishnan et al., 2004).

Recently, the research activities on SLN has gradually focused on the cosmetic and topical product, SLN as a topical carrier were used for topical delivery of several drugs including clotrimazole, prednicarbate and betamethasone 17-valerate and SLN was reported to have a skin targeting potential (Maia et al., 2000, Sivaramakrishnan et al., 2004, Souto et al., 2004, Song and Liu, 2005). SLN was found to have a skin targeting which can result in a high accumulation of podophyllotoxin in skin (Chen et al., 2006). The skin targeting of SLN for topical delivery aroused our interest. In this work, SLN was used for topical delivery of isotretinoin and the long-term aim is to explore a novel formulation with skin targeting effect for the treatment of severe acne. The present study focused on the preparation, characterization and skin targeting evaluation of the isotretinoin-loaded SLN (IT-SLN).