Thermoresponsive Gels

Abstract

Thermoresponsive gelling materials constructed from natural and synthetic polymers can be used to provide triggered action and therefore customised products such as drug delivery and regenerative medicine types as well as for other industries. Some materials give Arrhenius-type viscosity changes based on coil to globule transitions. Others produce more counterintuitive responses to temperature change because of agglomeration induced by enthalpic or entropic drivers. Extensive covalent crosslinking superimposes complexity of response and the upper and lower critical solution temperatures can translate to critical volume temperatures for these swellable but insoluble gels. Their structure and volume response confer advantages for actuation though they lack robustness. Dynamic covalent bonding has created an intermediate category where shape moulding and self-healing variants are useful for several platforms. Developing synthesis methodology-for example, Reversible Addition Fragmentation chain Transfer (RAFT) and Atomic Transfer Radical Polymerisation (ATRP)-provides an almost infinite range of materials that can be used for many of these gelling systems. For those that self-assemble into micelle systems that can gel, the upper and lower critical solution temperatures (UCST and LCST) are analogous to those for simpler dispersible polymers. However, the tuned hydrophobic-hydrophilic balance plus the introduction of additional pH-sensitivity and, for instance, thermochromic response, open the potential for coupled mechanisms to create complex drug targeting effects at the cellular level.

Keywords: LCST; UCST; drug delivery; hydrogel; micelle; multi-stimulus; organogel; thermoresponsive.

Figure 1

Gelling of injection below its upper critical solution temperature (UCST).

Figure 2

The UCST detail showing spinodal and binodal curves.

Figure 3

Relationship of the polymer form with temperature for a polymer showing UCST behaviour.

Figure 4

UCST, glass transition (Tg) and Berghmans point.

Figure 5

Gelatin coil and helix ‘crystalline’ regions.

Figure 6

Related EC-g-copolymer aqueous micelle systems that gel when aggregated beyond LCST or UCST respectively. Adapted from [124].

Figure 7

Dually responsive (i.e., two sequential stages LCST) micelle formation from poly(mPEGV₄₆₆)₁₈-b-PNIPAm₆₀ in water. Adapted from [145].

Figure 8

Unified LCST and USCT showing both theta points.

Figure 9

Hourglass pattern of some combined LCST and UCST behaviours.

Figure 10

Schizophrenic (reverse) PDEGEA-PMA micelles in ethanolic solution. Adapted from [152].

Figure 11

Swelling characteristics of hydrogels.