A pH- and thermo-responsive poly(amino acid)-based drug delivery system

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2015-12, Vol.136, p.562-569
• Main Authors: Liu, Na, Li, Bingqiang, Gong, Chu, Liu, Yuan, Wang, Yanming, Wu, Guolin
• Format: Article
• Language: English
• Subjects: Amino Acids - chemistry; Amino Acids - pharmacokinetics; Backbone; Copolymers; Doxorubicin; Drug delivery; Drug Delivery Systems; Hydrazones; Hydrogen-Ion Concentration; Nanoparticles; pH-sensitive; Poly(amino acid); Proton Magnetic Resonance Spectroscopy; Self assembly; Spectroscopy, Fourier Transform Infrared; Stacking; Stimuli-responsive; Thermo-responsive
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.09.057

[Display omitted] •Nanoparticles show sensitivities to both temperature and pH environment.•With a pH-sheddable hydrophilic corona.•DOX was successfully loaded via hydrophobic interaction and π–π stacking.•The drug release profiles displayed a pH and temperature-dependent behavior.•Readily taken up by cells due to shell shedding and the protonation of side tertiary amine groups induced positively charged surface. A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π–π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed.