Poloxamer/Carboxymethyl Pullulan Aqueous Systems-Miscibility and Thermogelation Studies Using Viscometry, Rheology and Dynamic Light Scattering.

Thermally-induced gelling systems based on Poloxamer 407 (PL) and polysaccharides are known for their biomedical applications; however, phase separation frequently occurs in mixtures of poloxamer and neutral polysaccharides. In the present paper, the carboxymethyl pullulan (CMP) (here synthesized) was proposed for compatibilization with poloxamer (PL). The miscibility between PL and CMP in dilute aqueous solution was studied by capillary viscometry. CMP with substitution degrees higher than 0.5 proved to be compatible with PL. The thermogelation of concentrated PL solutions (17%) in the presence of CMP was monitored by the tube inversion method, texture analysis and rheology. The micellization and gelation of PL in the absence or in the presence of CMP were also studied by dynamic light scattering. The critical micelle temperature and sol-gel transition temperature decrease with the addition of CMP, but the concentration of CMP has a peculiar influence on the rheological parameters of the gels. In fact, low concentrations of CMP decrease the gel strength. With a further increase in polyelectrolyte concentration, the gel strength increases until 1% CMP, then the rheological parameters are lowered again. At 37 °C, the gels are able to recover the initial network structure after high deformations, showing a reversible healing process.

Temperature/pH-Sensitive Double Cross-Linked Hydrogels as Platform for Controlled Delivery of Metoclopramide.

Novel double cross-linked (DC) hydrogels with pH-/temperature-sensitive properties were designed and developed. Therefore, linear pH-sensitive poly(methyl vinyl ether-alt-maleic acid) (P(VME/MA)) macromolecules were absorbed within a thermosensitive poly(N-isopropylacrylamide-co-hydroxyethylacrylamide)-hydrogel (PNH) and, subsequently, cross-linked together through a solvent-free thermal method. As a novelty, double cross-linked hydrogels were obtained from previously purified polymers in the absence of any solvent or cross-linking agent, which are generally harmful for the body. The new DC structures were characterized by FT-IR spectroscopy, SEM, swelling kinetic measurements, and mechanical tests. The resulting scaffolds exhibited interconnected pores and a flexible pattern, compared to the brittle structure of conventional PNH. The swelling kinetics of DC hydrogels were deeply affected by temperature (25 and 37 °C) and pH (7.4 and 1.2). Furthermore, the hydrogels absorbed a great amount of water in a basic environment and displayed improved mechanical properties. Metoclopramide (Met) was loaded within DC hydrogels as a model drug to investigate the ability of the support to control the drug release rate. The results obtained recommended them as convenient platforms for the oral administration of drugs, with the release of the largest part of the active principle occurring in the colon.