Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation.

Abstract:

UNLABELLED:The novel concept of modifying and enhancing the properties of existing functional micelles through self-complementary interactions has significant potential. In this study, a practical approach to living polymerization of functionalized thermoresponsive monomers enabled the incorporation of self-constituted multiple hydrogen bonded groups into micelles that have potential as supramolecular drug-delivery systems. Phase transitions and morphological studies in aqueous solution showed that the microstructure can be controlled to achieve well-defined vesicle-like micelles with respect to the strength of the hydrogen bond segment. Thus, the resulting micelles have a very low critical micellization concentration and very high loading capacity (16.1%), making the loading process extremely stable and efficient. Incorporation of the anticancer drug doxorubicin (DOX) affected the micellization process in aqueous solution and enabled fine-tuning of drug loading and precise control of drug release rate with excellent sensitivity. Release studies in vitro showed that DOX-loaded micelles exerted dose-dependent cytotoxicity against human liver carcinoma (HepG2) cells at the physiological temperature of 37°C. In addition, DOX-loaded micelles were efficiently endocytosed by the cancer cells, which may enable the micelles to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. This newly developed material may provide a potential route towards next-generation drug delivery vehicles. STATEMENT OF SIGNIFICANCE:A breakthrough innovation in water-based thermo-responsive polymers has enabled significant progress in developing smart stimuli-responsive nanocarriers by generating novel "supramolecular polymeric micelles" via self-complementary hydrogen-bonding interactions. These newly developed micelles exhibit extremely high micellar stability and drug loading capacity (up to 16%), excellent thermo-responsive behavior and precise control of drug release rate due to hydrogen-bond-induced physical cross-linking. In addition, doxorubicin-loaded micelles were efficiently endocytosed by the cancer cells, which allows them to serve as suitable vehicles for effective delivery of anticancer drugs to primary tumors and metastatic disease. Thus, this work provides a potential route for the development of next generation multifunctional nanocarriers that have improved safety and to increase the therapeutic efficacy of anticancer therapy.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Cheng CC,Chang FC,Kao WY,Hwang SM,Liao LC,Chang YJ,Liang MC,Chen JK,Lee DJ

doi

10.1016/j.actbio.2016.01.018

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

194-202

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(16)30018-6

journal_volume

33

pub_type

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