Tunable Upper Critical Solution Temperatures for Acrylamide Copolymers with Bile Acid Pendants

Abstract

Acrylamide derivatives of bile acids are chosen as a hydrophobic comonomer to copolymerize with acrylamide via reversible addition and fragmentation chain transfer (RAFT) polymerization to afford a series of copolymers of P(AAm-co-CAA). These copolymers exhibit a sharp and reversible insoluble-soluble transition in water upon heating to a mixing temperature (T) related to the upper critical solution temperature (UCST). T of these copolymers can be conveniently tuned to a practical temperature range, around 37 °C for biomedical applications. T rises with increasing molar fraction of the bile acid-based acrylamide and increasing concentration of the aqueous solution of the copolymers. The addition of a natural host molecule β-cyclodextrin lowered the T. The insoluble-soluble transition of the copolymers was also evidenced by dynamic light scattering and transmission electron microscopy. The biocompatible nature of the bile acids and β-cyclodextrins may make these copolymers potentially useful for biomedical applications.

Thermoresponsive polymer nanocarriers for biomedical applications

“…For the latter, it would be of interest to synthesize it from vinyl monomers instead of modifying a pre-existing polymer and comparing the two synthetic routes in terms of UCST tuning. Poly(acrylamide-co-cholic acid acrylamide), P(AAm-co-CAA), was copolymerized from a modified acrylamide monomer and yielded a copolymer exhibiting a concentration dependent UCST: 48 °C at 10 mg/mL down to 24 °C at 1 mg/mL in water [123]. Rather than having a copolymer, Seuring and Agarwal also showed that polymethacrylamide (PMAAm) has a UCST in water but only reported one example with the critical temperature at 57 °C at 10 mg/mL with a broad hysteresis [114].…”

Playing construction with the monomer toy box for the synthesis of multi‐stimuli responsive copolymers by reversible deactivation radical polymerization protocols

“…The three steps, however, were carried out in three different solvents, so the procedure was not one‐pot. UCST‐type responsive copolymers were obtained by RAFT polymerization of monomers functionalized with bile acid, 92 zwitterionic sulfobetaines, nitrile, diacetone acrylamide 93 . Multiple hydrogen bond forming monomers were polymerized using a PEG‐based CTA to obtain double hydrophilic block copolymers affording core‐stabilized, thermoresponsive micelles 94 .…”

Advances in thermo-responsive polymers exhibiting upper critical solution temperature (UCST)

“…Tpt of this copolymer can be easily tuned between 5 to 85°C by varying the molar fraction of bile acid monomer in the copolymers. Further, authors also demonstrate that the UCST of copolymer could also be controlled by using β-cyclodextrin (β-CD) as an additive in water [36]. Käfer et al [4] utilized poly(ethylene glycol) (PEG, M n2 000 g/mol) as a macro-azoinitiator to impart dual thermoresponsive property in P(AAm-co-AN) copolymer.…”

“…(CMDT -cyanomethyl dodecyl trithiocarbonate, AIBN -2,2′-Azoisobutyronitrile). Reproduced with permission from[36], Copyright © 2017 American Chemical Society.…”