Docetaxel in cationic lipid nanocapsules for enhanced in vivo activity

• Published in: Pharmaceutical development and technology Vol. 21; no. 1; pp. 76 - 85
• Main Authors: Jain, Ankitkumar S., Makhija, Dinesh T., Goel, Peeyush N., Shah, Sanket M., Nikam, Yuvraj, Gude, Rajiv P., Jagtap, Aarti G., Nagarsenker, Mangal S.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.01.2016
• Subjects: Animals; Anti-tumor; cationic nanocapsule; Cations; docetaxel; Female; Lipids - administration & dosage; Lipids - chemistry; Lipids - pharmacokinetics; Melanoma, Experimental - drug therapy; Melanoma, Experimental - metabolism; Mice; Mice, Inbred C57BL; Nanocapsules - administration & dosage; Nanocapsules - chemistry; non-everted rat-intestinal sac; Particle Size; Rats; Taxoids - administration & dosage; Taxoids - chemistry; Taxoids - pharmacokinetics; zebra fish; Zebrafish; zebra fish; non-everted rat-intestinal sac; cationic nanocapsule; Anti-tumor; docetaxel
• ISSN: 1083-7450; 1097-9867
• DOI: 10.3109/10837450.2014.971374

The usefulness of Docetaxel (DT) as an anti-cancer agent is limited to parenteral route owing to its very poor oral bioavailability. Thus, to improve its oral efficacy, DT was loaded in novel cationic lipid nanocapsules (DT CLNC). The DT CLNC possessed size of 130-150 nm, zeta potential of +72mV, adequate DT loading and over 95% encapsulation efficiency. TEM revealed capsular structure of DT CLNC. Lipolysis study indicated improved solubilization of DT by nanocapsules in comparison to DT solution. DT CLNC exhibited significantly higher release of DT in comparison to DT solution during in vitro permeation studies employing non-reverted rat-intestinal sac. Superior uptake of DT in zebra fishes exposed to DT CLNC resulted in greater apoptosis-based cell death as compared to those exposed to DT solution. This correlated well with the significantly superior (p < 0.05) anti-angiogenic activity of DT CLNC system over DT solution, in zebra fish model. DT CLNC also inhibited tumor growth in melanoma cell line induced tumors in C57BL/6 mice significantly, as compared to DT solution (p < 0.05). The DT CLNC system demonstrated adequate stability, with tremendous potential to improve oral efficacy of DT and can serve as an alternative to existing DT formulations available commercially for parenteral use.