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CC BY 4.0 · Pharmaceutical Fronts 2022; 04(03): e188-e196
DOI: 10.1055/s-0042-1757511
Original Article

Novel Docetaxel-Loaded Micelles Based on all-trans-Retinoic Acid: Preparation and Pharmacokinetic Study in Rats

Ya-Ni Yang   #
1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jia-Jia Cheng   #
1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jun He
1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Wei-Gen Lu
1   National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
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Abstract

Docetaxel (DTX) is a poorly soluble drug. The purpose of this study was to explore a DTX-loaded micelle delivery system using N-(all-trans-retinoyl)-L-cysteic acid methyl ester sodium salt (XMeNa) as the carrier materials. In this study, amphiphilic surfactant XMeNa was synthesized. Then, the blood biocompatibility and the value of critical micelle concentration (CMC) were assessed by a hemolysis test and pyrene-based fluorescent probe techniques, respectively. The XM-DTX micelles were prepared using the method of thin-film hydration, and characterized by dynamic light scattering and transmission electron microscopy (TEM). The entrapment efficiency (EE) and drug loading efficiency (DLE) were assessed by the ultrafiltration method. In vitro release and pharmacokinetic behaviors of XM-DTX micelles were performed in rats using Taxotere (a commercialized DTX injection) as a control. Our data confirmed the excellent blood biocompatibility of XMeNa as a carrier. XMeNa can self-assemble into micelles in aqueous media with a very low CMC (6.2 μg/mL). The average size and zeta potential of the XM-DTX micelles were 17.3 ± 0.2 nm, and −41.6 ± 0.3 mV, respectively. EE and DLE reached up to 95.3 ± 0.7% and 22.4 ± 0.2%, respectively, which may account for the high solubility of DTX in normal saline. The micelles were spherical in TEM with good dispersion and no aggregation and adhesion, and exhibited good stability after reconstitution over 8 hours. Results from in vitro release assay suggested a much slower release behavior of XM-DTX micelles in comparison to Taxotere. Additionally, XM-DTX micelles prolonged DTX retention in blood circulation, increased the area under the curve by 2.4-fold, and significantly decreased the clearance of the drug. Given above, the XM-DTX micelles could improve the solubility and the release of DTX. The amphiphilic surfactant XMeNa also exhibited great potential as a vehicle for exploring delivery of poorly water soluble drugs in the future.

Keywords

micelles - docetaxel - all-trans-retinoic acid - pharmacokinetic - surfactant

# These authors contributed equally to this work.




Publication History

Received: 17 April 2022

Accepted: 16 June 2022

Article published online:
19 September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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