Self-assembled hyaluronic acid-testosterone nanocarriers for delivery of anticancer drugs
Sprache des Titels:
The present research aims at controlled delivery of anticancer drugs camptothecin and doxorubicin through encapsulation in self-assembled hyaluronic acid (HA)-testosterone conjugates. The conjugates were obtained by functionalization of either natural sodium hyaluronate or hydrazide-modified HA derivatives with testosterone hemisuccinate. From 2.0 to 7.7% of HA disaccharide units were linked to testosterone via two types of linkers of different length. Fourier transform infrared and proton nuclear magnetic resonance spectroscopies confirmed modification of HA. Conjugation of hydrophobic testosterone to hydrophilic backbone of HA resulted in the self-assembly of amphiphilic HA-testosterone conjugates in aqueous medium and the formation of stable and negatively charged nanoparticles with hydrodynamic diameter ranging from 172 to 380?nm and ?-potential ranging from ?37 to ?26?mV, as evidenced from dynamic light scattering measurements. Examination of the dried conjugates by transmission electron microscopy revealed almost spherical particles of 50?100?nm size. Entrapment of camptothecin and doxorubicin in the hydrophobic core of HA-testosterone nanoparticles was performed with the drugs content of ca. 2.8?wt% and 3.5?wt% respectively. The sustained release of the anticancer drugs over 96?h was observed in phosphate buffered saline at pH 7.4. Cytotoxicity of camptothecin- and doxorubicin-loaded HA-testosterone nanoparticles against MCF-7 cancer cell line was found to be similar to the cytotoxicity of the free anticancer drugs. Based on the results of the in vitro studies, we can conclude that the developed HA-testosterone nanoparticles are promising candidates in chemotherapy treatments of cancers.