Construction of novel pH-sensitive hybrid micelles for enhanced extracellular stability and rapid intracellular drug release. Issue 107 (7th November 2016)

• Record Type: Journal Article
• Authors: Yin, Shaoping; Chang, Liang; Li, Tie; Wang, Guangji; Gu, Xiaochen; Li, Juan
• Is Part Of: RSC advances. Volume 6:Issue 107(2016)
• Page Start: 105957
• Page End: 105968
• Publication Date: 2016-11-07
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra23050d
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Novel pH-sensitive hybrid micelles with high entrapment efficiency were constructed to realize rapid intracellular drug release without premature release. Abstract : It is still a major challenge for successful cancer chemotherapy to design drug delivery systems with desirable extracellular stability and intracellular drug release. Here, novel pH-sensitive hybrid micelles were constructed by introducing positively charged arginine (Arg) into negatively charged micelles formed from a ternary graft copolymer (mPAL) comprising poly(acrylic acid) (PAA) as the backbone and methoxy poly(ethylene-glycol) (mPEG) and poly(lactide) (PLA) as the grafts to balance the extracellular stability and intracellular drug release. Paclitaxel (PTX) loaded hybrid micelles (PTX@mPAL/Arg) exhibited a desirable particle size (62.8 ± 2.9 nm), and a high entrapment efficiency (93.3 ± 2.9%). AFM and TEM images demonstrated the smooth surface and distinct spherical shape of the micelles. PTX@mPAL/Arg displayed high stability against dilution and serum, impeded drug release at physical conditions, and accelerated PTX release in mildly acidic medium. Blank micelles possessed satisfactory compatibility and would be safe for biomedical applications. PTX@mPAL/Arg micelles demonstrated much higher antitumor activity with low IC50 values of 0.67 and 0.20 μg mL −1 for A549 and HepG2 cells following 48 h incubation, respectively. A cellular internalization experiment indicated that the micelles could deliver and release cargo into the cytoplasm of HepG2 cells. Pharmacokinetic study in rats proved that PTX loaded micelles enhanced the AUC of PTX and prolonged circulation time in comparison to Taxol. These intelligent micelles with improved stability and drug release could be further studied as a promising delivery carrier for anticancer agents to improve therapeutic efficacy and to minimize adverse effects.