NIPAAm-containing amphiphilic block copolymers with tailored LCST: Aggregation behavior, cytotoxicity and evaluation as carriers of indomethacin, tetracycline and doxorubicin

Abstract

Nanocarriers based on amphiphilic block copolymers, with tailored temperature and pH responsiveness, were prepared. The hydrophilic blocks consist of temperature-sensitive [N-isopropylacrylamide (NIPAAm)] or NIPAAm plus pH-sensitive units [5-methacryloyloxy pentatonic acid (5MPA) or 4-methacryloyloxy benzoic acid (4MBA)], while the hydrophobic block is composed of n-hexyl acrylate (HA) or styrene (ST). Particle sizes were within the suitable range for the desired application (30–182 nm). Drug loading was achieved via an organic solvent-free method and a THF-buffer method leading to drug loadings of indomethacin, tetracycline and doxorubicin of up to 11, 11 and 60 wt%, respectively. In vitro release kinetics were performed under simulated physiological conditions (pH 7.4 and 37 °C; pH 6.0 and 40 °C) and show differences depending on the copolymer composition. The average kinetic data were well fitted to the mathematical model of Peppas. NIPAAm-containing copolymers were slight or non-cytotoxic for rat primary hepatocytes at concentrations less than 200 µg mL⁻¹. Some of the polymeric aggregates prepared may find application as pharmaceutical carriers.

Keywords:

• Polymeric drug delivery systems
• pH-sensitive
• cytotoxicity
• nanocapsules
• doxorubicin

Acknowledgements

This investigation was supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT) of Mexico under grants CB-2012/178709 and INFR-2016/26955; furthermore by the Universidad Autónoma de Sinaloa under grant PROFAPI2014/156. Technical support by Y. Cristerna-Madrigal (UAS), M. Díaz-Duarte and I.A. Rivero (IT-Tijuana) is gratefully acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.