Construction and in vitro/in vivo evaluation of 17-allylamino-17-demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers

Abstract

In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were constructed for the intravenous delivery of 17-allylamino-17-demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature using a mixture of glycerol monostearate and PEG₂₀₀₀-stearate as solid lipids, and medium-chain triglyceride as the liquid lipid. The results revealed that the morphology of the NLC was spheroidal. The particle size, zeta potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4 nm, −20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG existed as amorphous structures in the nanoparticles. In the in vitro release study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. In addition, 17AAG-PEG-NLC showed a significantly higher in vitro antitumor efficacy and longer retention time in vivo than 17AAG solution. These results indicated that 17AAG-PEG-NLC may offer a promising alternative to the current 17AAG formulations for the treatment of solid tumors.

• Antitumor
• in vitro drug release
• nanostructured lipid carriers

Declaration of interest

This work was supported by the Scientific Research Foundation of Administration of Traditional Chinese Medicine of Heilongjiang Province to Wang Zhi-yong (ZHY12-Z162), the Scientific Research Foundation of Health and Family Planning Commission of Heilongjiang Province to Wang Jing-hua (2014-280), the Scientific Research Fund of Higher Vocational Colleges of Heilongjiang Provincial Education Department to Yang Song-ling (11555091), and the Scientific Research Fund of Heilongjiang Provincial Education Department to Hou Shu-ying (12541560) and Wang Jing-hua (12541566).

The authors report no conflicts of interest.