Thermoresponsive Random Poly(ether urethanes) with Tailorable LCSTs for Anticancer Drug Delivery

Abstract

A new class of thermoresponsive random polyurethanes is successfully synthesized and characterized. Poly(ethylene glycol) diol (Mn = 1500 Da) and 2,2-dimethylolpropionic acid are reacted with isophorone diisocyanate in the presence of methane sulfonic acid catalyst. It is found that these polyurethanes are thermoresponsive in aqueous media and manifest a lower critical solution temperature (LCST) that can be easily tuned from 30 °C to 70 °C by increasing the poly(ethylene glycol) content. Their sharp LCST transitions make these random polyurethanes ideal candidates for stimuli-responsive drug delivery applications. To that end, the ability of these systems to efficiently sequester doxorubicin (up to 36 wt%) by means of a sonication/dialysis method is successfully demonstrated. Additionally, it is also demonstrated that accelerated doxorubicin release kinetics from the nanoparticles can be attained above the LCST.

Thermoresponsive Polyurethane Bearing Oligo(Ethylene Glycol) as Side Chain Without Polyol at Polymer Backbone Achieved Excellent Hydrophilic and Hydrophobic Switching

“…In other words, the hydrophilic and hydrophobic switching ability of the conventional polyurethane is still lower than that of the typical thermoresponsive polymers such as PNIPAM and POEGMA. Recently, a combination PEG‐based linear polyurethane with cationic or anionic groups successfully achieved sharp LCST, although the presence of ionic groups made the polyurethane sensitive to external stimuli such as pH and salt . Therefore, a gold standard structure of thermoresponsive polyurethane is yet to be attained.…”

Thermo‐responsive polyurethane hydrogels based on poly(ethylene glycol) and poly(caprolactone): Physico‐chemical and mechanical properties

“…By alternating hydrophilic PEG and hydrophobic segments, auto‐organized structures are formed as a consequence of micellization or sol–gel transitions in aqueous media, which is of great interest for biomedical applications . Sardon et al . reported a series of non‐crosslinked polyurethane copolymers composed of PEG as hydrophilic segment, isophorene diisocyanate as hydrophobic aliphatic isocyanate, and 2,2‐bis(hydroxymethyl)propionic acid as chain extensor.…”

Non-Isocyanate Polyurethane Soft Nanoparticles Obtained by Surfactant-Assisted Interfacial Polymerization

“…Finally, the incorporation of functional monomers in the NIPU nanoparticles was demonstrated as a means to sequester doxorubicin, a model anticancer drug. 12 Comparative study of different acyclic activated bis--carbonates reactivity towards PEG diamine. Acti-vated acyclic carbonates are ideal candidates for the prep-aration of NIPUs in aqueous media, since, despite their high reactivity towards primary amines, they are stable for up to 24 hours in aqueous media.…”