Albumin anchored docetaxel lipid nanoemulsion for improved targeting efficiency – preparation, characterization, cytotoxic, antitumor and in vivo imaging studies

Abstract

The aim was to develop albumin anchored docetaxel lipid nanoemulsion (ALNE) for improving tumor targeted delivery. The O/W lipid nanoemulsion, LNEs were prepared by homogenization and ultrasonication processes. The size of globules and zeta potential were measured by Malvern Zetasizer. Albumin was coupled to stearylamine containing lipid nanoemulsion (SALNE) globules using water soluble EDC reaction. The drug content and entrapment efficiencies for the LNEs were determined by the high-performance liquid chromatography. The in vitro cytotoxic studies of the delivery systems were performed on MCF-7 and Hela cells. The IC 50 values of ALNE on both the cell lines were statistically significant. The in vivo antitumor activity was tested on solid tumors induced in C57BL/6 mice. This study revealed that the percentage tumor inhibition for the groups treated with DLNE, SALNE and ALNE when compared with untreated control was found to be 55.62 ± 5.41%, 54.27 ± 4.85% and 80.01 ± 2.74%, respectively. Furthermore, in vivo distribution studies were carried out in breast cancer MDA-MB231 xenografted Balb/c mice. The LNEs were loaded with fluorescent DiD oil and the distribution in different organs after 6 h was tracked using Caliper life sciences in vivo imaging system. The studies revealed that ALNE was superior in tumor targeting activity when compared with DLNE and SALNE by 3.04 and 2.26 folds, respectively. The average radiance values of ALNE on the tumor tissue were statistically significant when compared with DLNE, SALNE at p < 0.01. In addition, this strategy can become a platform technology for other lipophilic drugs to target tumors.

• Albumin tagged docetaxel lipid emulsion
• antitumor study
• fluorescent imaging study
• improved tumor delivery
• tumor targeting

Acknowledgements

Gift samples of docetaxel were provided from M/s Dr Reddy’s Laboratories, Hyderabad, India and Egg Lecithin from M/s Lipoid, Ludwigshafen, Germany. Dr Y Narsimha Reddy, UCPSc, Kakatiya University, Warangal, Telangana, India for the help in cytotoxic studies. Mrs Ramadevi from NIN, Tarnaka, Hyderabad, India for the help in the iv administration of fluorescent LNEs during the in vivo imaging studies. Mr T. Dinesh and Dr G. Chandraiah, NIPER, Hyderabad, India for their help in animal studies. Mr Gulzaar Hasan from CCMB, Tarnaka, Hyderabad, India for his help in imaging study.

Declaration of interest

First author would like to thank UGC New Delhi for BSR Fellowship and financial support from UGC Major Research Project (F. No. 36-133/2008 (SR) Dated 26-03-2009). The authors would like to declare that they have no conflicts of interest.