Phase Behavior and Shrinking Kinetics of Thermo-Reversible Poly(N-Isopropylacrylamide-2-Hydroxyethyl Methacrylate)

Abstract

We study the thermodynamic properties of solutions of the physically gelling poly(N-isopropylacrylamide-2-hydroxyethyl methacrylate) [poly(NIPPAm-HEMA)]. We construct its phase diagram and characterize its kinetics of phase separation. This material belongs to a class of thermosensitive, “smart” polymers, that exhibit complex phase behavior. The copolymer studied is liquid at low temperatures and undergoes phase separation near 28°C, with negligible dependence on concentration. Above the transition temperature we observe coexistence between a polymer-dilute solution and a gel. We show that, upon quick heating, liquid solutions form a homogeneous gel that phase separates (shrinks) from a dilute polymer solution. We find that the evolution of the gel volume fraction is well described by a double exponential decay, indicating the presence of two shrinking regimes in a close parallel to the behavior of chemically cross-linked gels. The first stage is characterized by quick water ejection. In the second stage, slower shrinking is observed associated with internal reorganization of the polymers that allows the creation of gel-forming contacts.

A thermodynamic model of physical gels

“…The proposed dynamical description of the connectivity tensor can be incorporated into different schemes that describe the full gel. We note, in addition, that the idea that there exists at least two well differentiated processes during dynamic transformations of gels is well known, for both chemical (Suzuki et al, 1999) and physical gels (Leon et al, 2009). Our proposed scheme identifies explicitly these two different mechanisms as the reconstruction of internal structure and the simpler affined deformations induced by motion of the boundaries of the system.…”

“…We consider, in particular, the case of copolymers with a majority of NIPAAm monomers (Leon et al, 2009) that have been extensively used in drug delivery. For these materials, several prominent features appear in their phase diagrams.…”

“…In the temperaturevolume fraction phase diagram (Fig. 4 in Leon et al, 2009), there exists a critical temperature (i.e., LCST) at which the phase separation of sol and gel is presented. Above the LCST a system decomposes into a mixture of sol and gel states, i.e., coexistence states.…”

Injectable hydrogels

“…46 Usually, solutions are formulated at <30 wt % and deswell such that the final polymer concentration in the gel is about 50%, [47][48][49][50] so a significant fraction of water is lost during gelation. Rapid deswelling and syneresis (i.e., loss of the initially entrapped aqueous liquid) has been shown to be associated with fast drug release on heating above the LCST of NIPAAm-based physical gels.…”

Concanavalin A immobilized magnetic poly(glycidyl methacrylate) beads for antibody purification

“…Effective controlled drug delivery from NIPAAm‐based hydrogels is limited primarily by high burst release following gelation. As a poly(NIPAAm)‐based gel forms as a result of physical crosslinking, a homogeneous polymer‐rich phase (i.e., the gel) separates from a fraction of the original solvent and then tends toward an equilibrium composition 10, 16. Macroscopically, this is observed as shrinking and expulsion of solvent.…”