Precise control of drug release from dually responsive poly(ether urethane) nanoparticles

Abstract

A series of linear poly(ether urethane)s was synthesized based on alternating PEG-diisocyanate of different molecular weight and N-methyldiethanolamine containing ternary amino moieties. The molecular structures of the obtained copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectroscopy and gel permeation chromatography. In aqueous solution, the amphiphilic copolymers could self-assemble into nanoparticles, which showed temperature and pH dual-responsive character. The stimuli-responsive behavior was characterized by light transmission, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. The phase transition temperature (T p ) of the nanoparticles could be modulated by changing the molecular weight of the PEG segments. The encapsulation and release of doxorubicin (DOX) were investigated using the obtained polymeric nanoparticles as carriers. The in vitro experimental results showed that DOX release from the nanoparticles was significantly accelerated when it was conducted at a higher temperature and lower pH value. Importantly, only when the ambient temperature was higher than the corresponding T p , the drug release could be remarkably enhanced by the pH decrease. The system showed a temperaturetriggered pH-dependent drug release. Cell viability and microscopic observation of liver cells (HepG2 cells) treated with the DOX-loaded polymeric nanoparticles demonstrated that the therapeutic activity and the DOX distribution could be precisely controlled by the novel dual-responsive system.

Controlled Release of Protein from Biodegradable Multi-sensitive Injectable Poly(ether-urethane) Hydrogel

“…Polyurethanes are an important class of polymers that have found many applications as biomaterials, owing to their excellent physical properties and good biocompatibility. , A variety of in situ forming temperature- and pH-responsive poly(ether-urethane)-based hydrogels were developed by Lee’s group. − However, most of the copolymers mentioned above are not suitable for short-term drug delivery applications due to their slow biodegradation by enzymes in vivo. Recently, we have reported a series of multi-responsive degradable poly(ether-urethane) nanoparticles with a tunable structure, which are easily prepared by a facile one-pot approach by incorporating functional segments into the poly(ether-urethane) backbone. − As a further demonstration of this approach toward functional and tunable hydrogels, a series of pH, temperature, and redox potential multi-sensitive poly(ether-urethane)s were prepared for in situ forming hydrogels with fast degradation. In this study, (1) different ratios of poly(ethylene glycol) (PEG) and N -methyldiethanolamine (MDEA) possessing a tertiary amine group were used to tune the sol-to-gel window under physiological conditions (37 °C, pH 7.4) in order to prevent clogging during injection; (2) different ratios of 2,2′-dithiodiethanol (DiT) containing a disulfide bond were used to modulate the degradation time of the hydrogels in vivo; (3) insulin was used as a model protein to test its controlled release using the prepared multi-sensitive poly(ether-urethane) hydrogels.…”

PEG–lipid telechelics incorporating fatty acids from canola oil: synthesis, characterization and solution self-assembly

“…Novel polymeric materials have attracted much attention in advanced material science, due to the growing requirements of emerging technologies in slow drug release, [1][2][3] biosensing, 4 or tissue engineering. [5][6][7][8] Copolymers and/or polymeric conjugates containing hydrophilic and hydrophobic segments can form a micellar structure with a hydrophobic inner core and a hydrophilic outer shell in aqueous media as a result of their amphiphilic nature.…”

Shape Memory Polyurethanes Based on Zwitterionic Hard Segments

“…Recently, N -methyldiethanolamine (MDEA), which contains tertiary amine, has been used in the design of stimulus-responsive polyurethanes to have temperature and pH dual-responsive characteristics [ 15 ]. It is well known that the tertiary amine in the MDEA segment can be protonated to become ionic form [ 16 , 17 ].…”