Thermosensitive and photocleavable polyaspartamide derivatives for drug delivery

Abstract

The development of novel thermo‐ and photo‐dual‐responsive biodegradable polymeric micelles based on amphiphilic polyaspartamide derivatives (NB‐g‐PHPA‐g‐mPEG) for anticancer drug delivery is reported. The obtained polymers containing hydrophobic photocleavable o‐nitrobenzyl groups exhibit thermo‐ and photosensitivity. The micelles and paclitaxel‐loaded micelles based on the thermo‐ and photo‐dual‐sensitive polymers were prepared by a quick heating method without using toxic organic solvent. The paclitaxel release from the drug‐loaded micelles can be triggered under photoirradiation. Enhancement of the anticancer activity against HeLa cells was observed for paclitaxel‐loaded NB‐g‐PHPA‐g‐mPEG micelles after light irradiation, while the empty NB‐g‐PHPA‐g‐mPEG micelles with or without irradiation did not show any toxicity. Therefore, the thermo‐ and photo‐dual‐responsive NB‐g‐PHPA‐g‐mPEG micelles have a promising future applied as a light controlled drug delivery system for anticancer drugs. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2855–2863

Stimulus-Responsive Polymers Based on Polypeptoid Skeletons

“…O-nitrobenzyl group is stable in an acidic and alkaline environment and has highly controllable photochemical properties [ 96 , 97 ]. Li et al synthesized a diblock copolymer PEG-b-poly (n-(s- (o-nitrobenzyl)-thioethyl) glycine) (PEG-b-PNSN) by ring-opening polymerization.…”

Stimuli-Responsive Poly(aspartamide) Derivatives and Their Applications as Drug Carriers

“…Interestingly, the reaction product of PSI with NH 2 C 5 OH, denoted as PHPA, was completely soluble in water; while the reaction product of PSI with NH 2 C 6 OH was insoluble in water (test temperature: 0-100 • C). Since then, more and more temperature-responsive PASPAm derivatives containing alkanolamides moieties were designed and synthesized [33][34][35]. For instance, adopting the similar strategy of Kobayashi's group, Chu [36].…”

“…For designing lightresponsive polymers, photo-cleavage groups such as o-nitrobenzyl [92] were generally introduced. For instance, o-nitrobenzyl (NB) alcohol [35] was first activated by N,Ncarbonyldiimidazole and then grafted onto the pendant pentanolamide moieties of PHPA. When the obtained light-responsive NB-g-PHPA was treated under UV light at 365 nm for 30 min, the photo-cleavage o-nitrobenzyl carbonate ester linkage was broken and byproduct o-nitrosobenzaldehyde was detected.…”

“…The process of preparing drug-loaded nanoparticles from the temperature-responsive polymer aqueous solution is called the quick heating method. For example, Jiang et al reported that PTX was successfully loaded into micelles formed by temperature-responsive PASPAm derivatives through quick heating method, avoiding the use of toxic organic solvents [35,96,97]. Using temperature-responsive PEGylation phe-g-PHPA as drug carrier, the PTX-loading capacity was high, up to 29%, with a high loading efficiency of 99% [97].…”

Temperature Responsive Nanoparticles Based on PEGylated Polyaspartamide Derivatives for Drug Delivery

“…Up to now, three polyaspartamide anti-tumor formulations derived from L -aspartic acid (NK105 [ 17 ], NK911 [ 18 ] and NC6300 [ 19 , 20 ]) have been approved for clinical trials. The ring-opening reaction between poly(succinimide) (PSI) and amine compounds is an convenient strategy to synthesize polyaspartamide based polymers [ 21 , 22 ], and the stimuli responsiveness can be introduced by further modification of their side chains [ 23 , 24 , 25 ]. For example, the temperature responsive polyaspartamide based polymer phe-g-PHPA was prepared successfully by introducing phenyl alcohol (phe) to the side chains of PHPA, which was synthesized by the ring-opening reaction between PSI and 5-hydroxypentylamine, although the grafting efficiency of phe to PHPA was less than 50% [ 26 , 27 ].…”