Sustained release docetaxel-incorporated lipid nanoparticles with improved pharmacokinetics for oral and parenteral administration

• Published in: Journal of microencapsulation Vol. 34; no. 3; pp. 250 - 261
• Main Authors: Qureshi, Omer Salman, Kim, Hyung-Seo, Zeb, Alam, Choi, Jin-Seok, Kim, Hoo-Seong, Kwon, Jung-Eun, Kim, Myung-Sic, Kang, Jong-Ho, Ryou, Chongsuk, Park, Jeong-Sook, Kim, Jin-Ki
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-04-2017
• Subjects: Administration, Oral; Antineoplastic Agents - pharmacokinetics; bioavailability; Delayed-Action Preparations; docetaxel; Drug Carriers - chemistry; Humans; Lipid nanoparticles; Lipids - chemistry; MCF-7 Cells; Nanoparticles - chemistry; pharmacokinetics; sustained release; Taxoids - administration & dosage; Taxoids - pharmacokinetics; pharmacokinetics; bioavailability; docetaxel; sustained release; Lipid nanoparticles
• ISSN: 0265-2048; 1464-5246
• DOI: 10.1080/02652048.2017.1337247

The aim of this study was to develop docetaxel-incorporated lipid nanoparticles (DTX-NPs) to improve the pharmacokinetic behaviour of docetaxel (DTX) after oral and parenteral administration via sustained release. DTX-NPs were prepared by nanotemplate engineering technique with palmityl alcohol as a solid lipid and Tween-40/Span-40/Myrj S40 as a surfactants mixture. Spherical DTX-NPs below 100 nm were successfully prepared with a narrow particle size distribution, 96% of incorporation efficiency and 686 times increase in DTX solubility. DTX-NPs showed a sustained release over 24 h in phosphate-buffered saline and simulated gastric and intestinal fluids, while DTX-micelles released DTX completely within 12 h. The half-maximal inhibitory concentration (IC
50
) of DTX-NPs against human breast cancer MCF-7 cells was 1.9 times lower than that of DTX-micelles and DTX solution. DTX-NPs demonstrated 3.7- and 2.8-fold increase in the area under the plasma concentration-time curve compared with DTX-micelles after oral and parenteral administration, respectively.