Lower critical solution temperature versus volume phase transition temperature in thermoresponsive drug delivery systems

Abstract

Abstract. One of the most subtle problem in the characterization of thermoresponsive polymers is the evaluation of the relationship between the lower critical solution temperature (LCST) of the linear polymer and the volume phase transition temperature (VPTT) of the corresponding hydrogel. Here, the LCST and the onset temperature of linear poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) has been determined under pseudo-physiological conditions by cloud point (CP) measurements and by microcalorimetric analysis. The LCSTs, as well as the onset temperatures, determined by the CP method, decrease with increasing the concentration of the polymer solution. On the contrary, microcalorimetric analyses give almost the same values for LCSTs and the onset temperatures regardless of polymer concentration. The VPTT of the hydrogel, determined by the blue dextran method, was found to be closely similar to the LCST of the concentrated polymer solution (10%, w/v), determined by the CP method. In fact, the hydrogel could be considered as a concentrated polymer solution whose concentration could be related to the amount of water retained by the hydrogel. Hydrogel microspheres have been also reported to release diclofenac, a drug model system, in a pulsating way at temperatures slightly below and above the VPTT.

Smart poly(oligo(propylene glycol) methacrylate) hydrogel prepared by gamma radiation

“…1a, it is evident that the LCST value determined by the CP method decreases with increasing OPGMA concentration. This is consistent with other studies regarding LCST behaviour [24,48]. The obtained LCST values clearly show some differences with pH.…”

“…1c), confirms that radiation induced polymerisation and crosslinking of OPGMA involves the breaking of terminal carbon-carbon double bonds [57]. One of the most subtle problems in the characterisation of thermoresponsive polymers is evaluating the relationship between the lower critical solution temperature (LCST) of the linear polymer and the volume phase transition temperature (VPTT) of the corresponding hydrogel [48]. Namely, small organic compounds as well as polymeric structures can undergo a transition from a soluble to an insoluble phase upon heating.…”

“…In general, physically and chemically crosslinked hydrogels used in biomedical applications are prepared starting from more concentrated polymer solutions (at least 5-10 wt%) [48]. In the case of a aqueous OPGMA solution with a concentration of 10 wt%, the solution cannot be turned from clear to turbid since the aqueous OPGMA solution is very turbid irrespective of temperature (insert 1 in Fig.…”

“…The LCST profile was determined from the absorbance at 650 nm [24]. Similar to previous reports, the temperature at a normalised absorbance value of 0.5 was defined as being the LCST [3,9,48]; strictly speaking this is the cloud point (CP) of the solution.…”

“…The VPTT values of thermoresponsive hydrogels are generally determined by the standard equilibrium swelling ratio method [48][49][50]. However, this method, which allows the water retained at different temperatures to be determined, is unreliable since the gel is removed from solution at room temperature during weight measurements.…”