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Preparation of poly(N-isopropylacrylamide)-block-(acrylic acid)-encapsulated proteinaceous microbubbles for delivery of doxorubicin

Year: 2017

Journal: Colloid Surf. B-Biointerfaces, Volume 154, JUN 1, page 115–122

Authors: Ma, Xiaochen; Liu, Qingxia

Keywords: Proteinaceous microbubbles; BSA; Doxorubicin; Poly(NIPAM-b-AAc); Temperature-controlled releasing; Premature release; Electrostatic interactions

Inspired by theranostic technologies, we electrostatically loaded proteinaceous microbubbles (MBs) with a model drug, doxorubicin (Dox) to couple their utilizations in diagnostic imaging with drug loading. A temperature-sensitive polymer, poly(N-isopropylacrylamide-block-acrylic acid) (poly(NIPAM-b-AAc)) was used to encapsulate the Dox-loaded MBs to prevent premature release and to control the Dox release thermally. An LCST of 39 degrees C, slightly higher than normal body temperatures, enables the release of Dox through a conformational change of the polymer shell upon moderate heating. The successive loadings of Dox and poly(NIPAM-b-AAc) were confirmed by fluorescent confocal laser scanning microscope (CLSM) imaging, zeta potential measurement, Fourier transform infrared spectroscopy (FTIR), and quartz crystal microbalance with dissipation (QCM-D). Without a polymer shell, Dox-loaded MBs showed a poor in vitro retention of Dox at room temperature, releasing similar to 75% within 8 h, whereas the polymer-shelled, Dox-loaded MBs did not show any premature release of Dox. From 37 degrees C to 39 degrees C, the cumulative release of Dox from the polymer-encapsulated MBs was increased from similar to 20 to similar to 90% over a period of 18 h based on in vitro release testing (IVRT). However, the release profiles of Dox from the shell-free, Dox-loaded MBs did not exhibit any similar temperature-controlled behavior, releasing similar to 90% of Dox within 5 h at both 37 degrees C and 39 degrees C. (C) 2017 Elsevier B.V. All rights reserved.