Correlation between the composition of PLA-based folate targeted micelles and release of phosphonate derivative of betulin

Abstract

There are increasing numbers of developed nanocarriers for anticancer drug delivery in the aim to avoid side effects of the conventional chemotherapy. Filomicelles with folic acid (FA) as a targeting moiety are a novel approach that can potentially maximize therapeutic efficacy while minimizing side effects. The aim of this study was to analyze the influence of composition of PLA-based micelles functionalized with folic acid on their drug encapsulation and release properties as well as cytotoxic activity against cancer cells. Micelles were obtained from combination of poly (l-lactide)-Jeffamine-folic acid (PLA-Jeff-FA) and poly (l-lactide)-poly (ethylene glycol) (PLA-PEG) or poly (l-lactide)-poly (ethylene glycol)-folic acid and PLA-PEG. E−29-diethoxyphosphoryl-28-O-propynoylbetulin as an anticancer agent was encapsulated into micelles. The in vitro biocompatibility of drug-free micelles was confirmed as well as cytotoxicity of E−29-diethoxyphosphoryl-28-O-propynoylbetulin loaded micelles against FR-positive SK-BR-3 cells. The micelles provided a release of an active agent for over 260 h. However, the micelles characterized differences in morphology, drug loading and release properties. The hydrophobic block length has been identified as a factor that may be used to control inter- and intramolecular interactions and, in consequence, micelle's properties, e.g. drug encapsulation efficiency and release rate.