In vitro–in vivo evaluation of hyaluronic acid-based amphiphilic copolymers for tumour targeted delivery: the role of hydrophobic groups

Abstract

Polymeric micelles are widely used as suitable nano-carriers for a variety of therapeutic applications. Exploring the role of hydrophobic groups on the properties of the amphiphilic carrier and micelles were the aim of this study. Using hyaluronic acid (HA), cholesterol (CHOL) and octadecanoic acid (OA), two amphiphilic polymers were prepared and fully characterized by ¹H NMR, FTIR and DSC. Compared with HA–SA–CYS–OA, HA–SA–CYS–CHOL had a lower critical micellar concentration (CMC) producing docetaxel (DTX)-loaded micelles of a smaller particle size, higher encapsulation efficiency (EE) and drug loading (DL%). However, HA–SA–CYS–OA had the greater EE when loaded with coumarin-6 (Cou6), suggesting that hydrophobic groups had a degree of selectivity for drugs. Cellular uptake demonstrated that the two micelles clearly increased the internalization of DTX via CD44 receptor-mediated endocytosis. In vitro cytotoxic experiments showed that HA–SA–CYS–OA micelles were generally more cytotoxic to MCF-7, A549 and S-180 cells on account of the toxicity of octadecanoic acid while in vivo animal experiments confirmed that HA–SA–CYS–CHOL micelles exhibited better tumor-targeting properties and antitumor effects. From these preliminary evaluations, it is possible to conclude that hydrophobic groups not only affect the stability and drug-loading capacity of the amphiphilic carriers, but also influence the distribution, metabolism, excretion and ultimately, the antitumor efficacy of micelles.