Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release

Abstract

The objective of this study was to prepare the CHS-mPEG/CHS-dFdC nanoformulation could be administrated through intravenous injection in nude mice. Particularly, CHS-mPEG was selected to co-assemble with CHS-dFdC to improve the prodrug concentration and enhance the stability of nanoformulation. The nanoformulation could be prepared by codissolution–coprecipitation. All of the nanoformulations kept stable in PBS at 4 °C or simulative human plasma at 37 °C. As molar ratios of CHS-mPEG₁₉₀₀/CHS-dFdC increased from 0.1/1 to 2/1, the weight concentration of CHS-dFdC increased from 2.5 to 15 mg/mL. It was found the optimal CHS-mPEG₁₉₀₀/CHS-dFdC nanoformulation displayed controlled drug release in simulative lysosome condition. The amount of released dFdC reached up to 90% within 10 h. It also exhibited enhanced cellular uptake ability, 7-folds higher than that of dFdC during 2.5 h incubation. And it showed superior cytotoxicity resulted from the enhanced cellular uptake ability on BxPC-3 cells.

Keywords:

• CHS-mPEG
• CHS-dFdC
• intracellular drug controlled release
• enhanced cellular uptake
• nanoformulation

Acknowledgements

The research work was supported by the National Natural Science Foundation of China (51573050), the Fundamental Research Funds for the Central Universities (XDJK2016C033 and XDJK2016A017).

Disclosure statement

No potential conflict of interest was reported by the authors.