Preparation and characterization of lipid emulsions containing styrene maleic acid copolymer for the development of pH-responsive drug carriers.

Lipid emulsions are potential carriers for poorly water-soluble drugs. Previously, we revealed that lipid nanoparticles complexed with styrene maleic acid copolymer (SMA) disintegrate under acidic pH. In the present study, SMA-containing lipid emulsions (SMA emulsions) were prepared and their physicochemical and biological properties were examined to test whether SMA emulsions could be used as a trigger to facilitate drug release in response to pH reduction. By sonicating lipid and SMA mixtures, homogeneously sized SMA emulsion particles were prepared as verified via dynamic light scattering and transmission electron microscopy. Upon the reduction of solution pH, disintegration of SMA emulsions was observed, which may be utilized for drug release at mildly acidic pH. In addition, the sensitivity to pH changes could be controlled by altering the lipid composition. Serum proteins bound to SMA emulsions were analyzed to predict the metabolic fate upon intravenous injection. Predictably, apolipoproteins were abundantly bound, suggesting that SMA emulsions should avoid being recognized as foreign substances. Furthermore, subcellular distribution studies using a human breast cancer cell line (MDA-MB-231) demonstrated that SMA emulsions localize to lysosomes, which have a lower pH. These results suggest that SMA emulsions could be promising pH-responsive drug carriers.