ABSTRACT: In order to develop a novel self-assembly as a means of cancer cell targeting, self-organized nanogels were prepared from acetylated hyaluronic acid with low molecular weight (AC-HA(LM)). Three samples were obtained (AC-HA(LM)1, 2 and 3) with degrees of acetylation, 0.8, 2.1, or 2.6 acetyl groups per unit (2 glucose rings) of HA(LM) to control their hydrophobicity. The mean diameters of AC-HA(LM)2 and 3 were less than 300 nm with unimodal size distribution, while that of AC-HA(LM)1 was above 400 nm. The critical aggregation concentrations (CAC) of the nanogels in distilled water were < 1 x 10(-1) mg/mL. The doxorubicine (DOX) loading efficiencies and loading contents of AC-HA(LM) increased as the degree of acetylation increased, in particular, the loading efficiency of AC-HA(LM)3 reached above 90%. AC-HA(LM)3 nanogels showed IC(50) at 1300 ng/mL of the DOX concentration against HeLa cells (with HA-binding receptors) similar to free DOX. For monitoring of specific interaction with a carcinoma cell line (HeLa cells with HA-binding receptors), AC-HA(LM)3 was labeled with FITC and observed with a confocal microscope. HeLa cells were strongly luminated by interactions with fluorescence-labeled AC-HA(LM)3 nanogels; however, this luminance was significantly decreased by competition inhibition of free HA. This result indicates that modified HA maintains the ability to interact with HA-binding receptors. The selective cytotoxicity and interaction of AC-HA(LM) nanogels may help reduce side effects of anti-cancer drugs in clinical use.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 07/2010; 40(4):367-75. · 2.61 Impact Factor