Production of drug-loaded lipid nanoparticles based on phase behaviors of special hot microemulsions

Abstract

The phase behaviors of special hot microemulsion were studied and used to realize the controllable production of drug-loaded nanostructured lipid carriers (NLCs). The home-made detection instrument of phase diagram which includes a very important thermostatic unit was applied to monitor the phase change of polyoxyethylene(40)stearate (S40)/polyoxyethylene-b-polyoxypropylene (F68)/glycerol monostearate (GMS)+oleic acid (OA)/water microemulsion system. The several main phase regions, such as oil-in-water (O/W) microemulsion, water-in-oil (W/O) microemulsion, and liquid crystal region, were all founded in the phase diagram of the above-mentioned system. The O/W microemulsion region was the most important region for the preparation of lipid nanoparticles. The drug-free GMS/OA-NLCs and retinoid acid (RA)-loaded RA-GMS/OA-NLCs were produced by direct cooling of hot microemulsions which were obtained according to the component ratio in the corresponding O/W microemulsion region in their phase diagrams. The two obtainable NLC suspensions were all transparent and clear due to the very smaller average diameter of 10.2±0.2nm of both NLCs by means of photon correlation spectroscopy (PCS) measurements. TEM images showed that both SLNs were all irregular spherical particles with the diameter of about 10nm. Zeta potential of both NLCs were in the range of −40.7±0.8mV, showing the good stability of both NLCs. Such NLCs could be used as not only drug carriers, but also other healthy-related products such as nanoscale carriers of nutrients and cosmetics additives.