LIPID-BASED BARRIERS FOR DRUG RELEASE FROM NANOPARTICLES

Abstract

Forming and manipulating nanoparticles as drug carriers is a rapidly expanding field in pharmaceutics. Past work using flash nanoprecipitation of the hydrophilic drug polymyxin B and oleic acid produced unusual results. These nanoparticles did not show the expected continuous release of the drug, but rather a single initial release. It was suspected that a lamellar liquid crystal phase is formed around the polymyxin B due to the interaction of pure oleic acid with water. If oleic acid behaves the same way with less hydrophilic drugs, then there would be more prospective drugs for targeted drug release by pH and salt. However, oleic acid did not behave the same way with two hydrophobic drugs, cinnarizine and clofazimine. Excess oleic acid stabilized polymyxin B, whereas excess oleic acid destabilized cinnarizine and had no stability effect on clofazimine, the most hydrophobic drug. No correlation was presented between hydrophobicity and oleic acids effect on stability, but there may be a correlation between pKa and oleic acids effects. Excess oleic acid stabilized the drug as pKa increased. This hypothesis would have to be tested in further studies. In this project, variables that could affect clofazimine-oleate nanoparticle size was also explored. It was determined that salty and acidic environments have little effect on changing clofazimine-oleate nanoparticle size. This result shows potential for using these particles for targeting acidic and salty environments of the body, an unexplored approach to drug delivery.