In-Situ Thermoreversible Gelation of Block and Star Copolymers of Poly(ethylene glycol) and Poly(N-isopropylacrylamide) of Varying Architectures

Abstract

We report the development of a new gelation mechanism and a new family of polymers that self-assembles to form gels in a thermoreversible fashion. The polymers are block or star copolymers with a central hydrophilic poly(ethylene glycol) (PEG) segment (A) and temperature responsive poly(Nisopropylacrylamide) (PNIPAAm) terminal segments (B). Copolymers of various architectures, AB, A(B) 2, A(B)4, and A(B)8, were synthesized to investigate the structures and properties relationship. At 5 °C, the viscosities of 20 wt % solutions were between 700 and 950 cP, and they could be easily injected through a 25 G needle. Upon warming to body temperature, A(B)2, A(B)4, and A(B)8 formed a strong associative network gel with aggregates of PNIPAAm segments acting as physical cross-links, whereas AB formed a weaker gel by micellar packing and entanglement. The values of elastic modulus, loss tangent, and yield strength were 1000-2500 Pa, 0.24-0.62, and 200-860 Pa, respectively. The gelation kinetic was fast; a typical gelation time for a solution of 5 mL in volume was less than a minute. No significant syneresis was observed after 2 months at 37 °C. DSC results indicated that the thermal behavior of material was completely reversible even after 30 heat-and-cool cycles. These materials are promising candidates for in-situ gelation applications such as injectable drug delivery, tissue engineering scaffolds, and anatomical barriers.

A polymeric micelle system with a hydrolysable segment for drug delivery

“…The formed solid was dissolved in distilled water to form 100 mg/ml solution and centrifuged 0.5 hour (10,000 rpm, Eppendorf 5415C) at 40°C to separate the unreacted PEO. Colorimetric analysis was carried out with Ce(IV) as a colorimetric reagent to verify that no unreacted PEO remained [11]. The precipitated copolymer products were dried under reduced pressure.…”

Smart hydrogels based on responsive star-block copolymers

“…reported on linear and star-shaped block copolymers of PEO and PNiPAAm and found that (PEO-PNiPAAm) 4 showed a sol-gel transition to a strong gel at 37 °C and exhibited the highest moduli compared to the other polymers. 71 Fechler et.al. reported 4-arm stars with PEO inner blocks and P(DEGMA-co-OEGMA) outer blocks, which formed fully reversible free-standing hydrogels at 15 wt% upon heating.…”

“…68 Second, using multi-arm (AB) x type copolymers lowers the critical gelation concentration by eliminating the micelle formation step. [69][70][71] This will be discussed below.…”

The Use of Ultrasound and Micelles in Cancer Treatment

“…In their experiments, they used a label (Lysosensor Green) that fluoresces more strongly in a lysosome or an endosome, where the pH is more acidic (about 4.8), compared to a pH of 7.1 outside these compartments (83,84). Flow cytometry was then used to analyze cells exposed to US and P105 micelles with Lysosensor Green.…”