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With the purpose of reducing side effects in anticancer therapy, the micelles of a novel reduction-activated copolymer with biomimicking phosphorylcholine, poly(ε-caprolactone)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-ss-PMPC) are developed. The well-suitable nanosize of micelles with good physiological stability (approximately 50 nm, 2.5 μg/mL) can be quickly internalized into cells due to bioinspired phosphorylcholine property and mainly located in endo/lysosomes. The reduction response of micelles is confirmed by size change and accelerated drug release under reducing environment, proved as better anticancer efficacy in comparison to insensitive micelles. Pharmacokinetics and in vivo studies demonstrate that redox-activated polymeric micelles can prolong blood transportation, facilitate passive target and accumulate in tumor site, and prompt drug release in cytoplasmic redox environment, behaving as much better antitumor efficiency than control and positive DOX·HCl groups. More importantly, the DOX-loaded micelles considerably reduce side effects and systematic toxicity. Therefore, this work fabricated an innovative bioinspired nanosystem via a facile strategy to achieve effective anticancer therapy., (Copyright © 2018. Published by Elsevier B.V.)

In order to prepare pH and redox sensitive micelles, amphiphilic copolymers of poly (epsilon-caprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) (PCL-PDEA) and disulfide-linked poly(ethyl glycol)-poly(epsilon-caprolactone) (mPEG-SS-PCL) were synthesized. The double-sensitive micelles were prepared simply by solvent-evaporating method with the mixed two copolymers. The pH sensitivity of the mixed micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic lighting scattering (DLS) and the redox sensitivity of the mixed micelles was testified by the change of micellar morphous observed by scanning electron microscope (SEM). In vitro drug release showed that drug-loaded mixed micelles (mass ratio 5:5) could achieve above 90% of drug release under low pH and reducing condition within 10h. Moreover, the drug-loaded mixed micelles (mass ratio 5:5) showed the largest cellular toxicity compared with other drug-loaded micelles, while blank mixed micelles exhibited no toxicity. These results meant that the mixed micelles composed by the two amphiphilic copolymers can enhance intracellular drug release. It is concluded that the newly developed mixed micelles can serve as a potential drug delivery system for anticancer drugs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Internalization of drugs by cancer cells is a crucial factor to impact cancer treatment effect. Curcumin, having inhibitory effect on a variety of cancers, was encapsulated into micelles of six-arm star-shape poly(ε-caprolactone)-b-poly(2-methacryloyloxyethylphosphorylcholine) (6sPCL-PMPC) in order to enhance its concentration in blood and cellular uptake. Micelles and curcumin-loaded micelles were prepared by the solvent-evaporation method. Drug-loading content and drug-loading efficiency could be achieved as high as 18.9 and 98%. MTT results showed that these curcumin-loaded micelles displayed significant cell cytotoxicity, while these blank micelles were noncytotoxic. The curcumin-loaded 6sPCL-PMPC micelles showed higher efficiency to kill HeLa cells than that of curcumin-loaded PCL-PEG micelles. The cellular uptake study indicated that the curcumin encapsulated into 6sPCL-PMPC micelles was ingested more by HeLa cells than the curcumin encapsulated into PCL-PEG micelles. In conclusion, the micelles with phosphatidylcholine (PC) groups as their exterior can greatly enhance the uptake by HeLa cells and the cytotoxicity of curcumin due to excellent internalization by cancer cells.

Polymer micelles for anticancer drug delivery have shown many advantages. In this study, poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL-PMPC) with bio-inspired structure self-assembled into small and uniform micelles as traditional poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-PEG). The in vitro and in vivo anti-tumor efficiency of PCL-PMPC and PCL-PEG micelles were detailedly evaluated. The both micelles were able to load DOX with high efficiency. PCL-PMPC micelles exhibited faster drug release at pH 5.5 than that of PCL-PEG micelles. Confocal laser scanning microscopy and flow cytometry results showed that PCL-PMPC micelles were more effectively internalized by tumor cells. DOX-loaded PCL-PMPC micelles presented higher cytotoxicity to tumor cells. PCL-PMPC micelles displayed not only longer circulation time in pharmacokinetics investigation, but also higher accumulation at the tumor site in in vivo imaging study in comparison with PCL-PEG micelles. More importantly, in a tumor model DOX-loaded PCL-PMPC micelles showed better therapeutic efficacy than DOX-loaded PCL-PEG micelles along with mild side effects. Therefore, PCL-PMPC micelles are deemed to be promising drug carriers for cancer therapy. [ABSTRACT FROM AUTHOR]

Polymeric micelles are one important class of nanoparticles for anticancer drug delivery, but the impact of hydrophobic segments on drug encapsulation and release is unclear, which deters the rationalization of drug encapsulation into polymeric micelles. This paper focused on studying the correlation between the characteristics of hydrophobic segments and encapsulation of structurally different drugs (DOX and β-carotene). Poly(ϵ-caprolactone) (PCL) or poly( l -lactide) (PLLA) were used as hydrophobic segments to synthesize micelle-forming amphiphilic block copolymers with the hydrophilic methoxy-poly(ethylene glycol) (mPEG). Both blank and drug loaded micelles were spherical in shape with sizes lower than 50 nm. PCL-based micelles exhibited higher drug loading capacity than their PLLA-based counterparts. Higher encapsulation efficiency of β-carotene was achieved compared with DOX. In addition, both doxorubicin and β-carotene were released much faster from PCL-based polymeric micelles. Dissipative particle dynamics (DPD) simulation revealed that the two drugs tended to aggregate in the core of the PCL-based micelles but disperse in the core of PLLA based micelles. In vitro cytotoxicity investigation of DOX loaded micelles demonstrated that a faster drug release warranted a more efficient cancer-killing effect. This research could serve as a guideline for the rational design of polymeric micelles for drug delivery. [ABSTRACT FROM AUTHOR]