Degradable polymeric nanoparticles by aggregation of thermoresponsive polymers and “click” chemistry

Abstract

This study describes a novel approach to the preparation of crosslinked polymeric nanoparticles of controlled sizes that can be degraded under basic conditions. For this purpose thermoresponsive copolymers containing azide and alkyne functions were obtained by ATRP of di(ethylene glycol) monomethyl ether methacrylate (D) and 2-aminoethyl methacrylate (A) followed by post polymerization modification. The amino groups of A were reacted with propargyl chloroformate or 2-azido-1,3-dimethylimidazolinium hexafluorophosphate, which led to two types of copolymers. Increasing the temperature of aqueous solutions of the mixed copolymers caused their aggregation into spherical nanoparticles composed of both types of chains. Their dimensions could be controlled by changing the concentration and heating rate of the solutions. Covalent stabilization of aggregated chains was performed by a "click" reaction between the azide and alkyne groups. Due to the presence of a carbamate bond the nanoparticles undergo pH dependent degradation under mild basic conditions. The proposed procedure opens a route to new carriers for the controlled release of active species.

Thermoresponsive P(HEMA-co-OEGMA) copolymers: synthesis, characteristics and solution behavior

“…The signicant effect of concentration on T cp for polymers based on monomers from the OEGMA group is usually observed. 15,62 P(HEMA-co-OEGMA)s behavior in PBS solution…”

Thermoresponsive Polymer Gating System on Mesoporous Shells of Silica Particles Serving as Smart Nanocontainers

“…There have been numerous examples of nanocarriers composed of thermoresponsive polymers that can be applied for releasing active substances using either temperature-triggered or other types of mechanisms [23][24][25][26][27]. One may observe also a growing interest concerning mechanized silica nanoparticles that utilize supramolecular nanovalves responding to external stimuli for controlled release of encapsulated substances [28][29][30][31][32].…”

Recent Developments in the Area of Click‐Crosslinked Nanocarriers for Drug Delivery

“…Similarly, CuAAC is a general method for the synthesis of click‐crosslinked nanoparticles; that is, viral nanoparticles crosslinked with “clickable” fluorescent crosslinkers at the interface, drug nanocrystals with PEG nanocages as non‐sheddable stabilizers, drug‐conjugated biodegradable nanoparticles by click‐crosslinking in miniemulsion, size‐restricted robust and functionalizable hydrophilic nanocrystals, degradable polymeric nanoparticles built from thermoresponsive polymers, and light‐sensitive dextran‐covered nanoparticles . For example, Cheng et al.…”