Doxorubicin hydrochloride (DOX) is one of the widely used antineoplastic agents in treating various cancers, yet it is always associated with the occurrence of adverse reactions that limit its clinical use. Currently, encapsulating DOX in micelles may represent a promising strategy to reduce toxicity and side effects of the drug. This study aimed to explore a novel acitretin-based surfactant (ACMeNa) with good solid stability to encapsulate DOX to form micelles (ACM-DOX). In this work, ACM-DOX micelles were prepared by a microfluidic method free of organic solvents. The characteristics of ACM-DOX micelles were assessed, including morphology, particle size, stability, entrapment efficiency, and drug loading. An in vitro cytotoxicity experiment of the micelles on MDA-MB-231 (a human breast cancer cell line) was also performed. The micelle formation mechanism suggested that the insoluble ACMeNa/DOX complex was formed by electrostatic interaction, and subsequently encapsulated by self-assembly into micelles. The designed ACM-DOX micelles had an average particle size of 19.4 ± 0.2 nm and a zeta potential of −43.7 ± 2.4 mV, with entrapment efficiency and drug loading efficiency of 92.4 ± 0.5% and 33.4 ± 0.3%, respectively. The ACM-DOX micelles had worm-like structures under a Cryo-transmission electron microscope and exhibited good stability within 8 hours after reconstitution and 4- to 32-fold dilution of its reconstituted solution. ACM-DOX micelles released 80% of DOX within 24 hours in a medium of pH = 5.0, and its drug profile can be described by a first-order model. Moreover, ACM-DOX micelles showed cytotoxicity against MDA-MB-231 in a dose-dependent manner, and displayed a higher antitumor activity as compared with free DOX, with IC50 values of DOX and ACM-DOX micelles being 6.80 ± 0.50 and 4.64 ± 0.32 μg/mL, respectively. Given above, ACMeNa has great application potential as a DOX carrier for the treatment of cancers.
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.
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