Simone F. Medeiros

Chapter 10 – Nanostructured Hydrogels

Polymer systems can be developed into a variety of functional forms to meet industrial and scientific applications. In general, they are presented in four common physical forms: (1) linear free chains in solution, (2) covalently or physically cross-linked reversible gels, (3) micro and nanoparticles, and (4) chains adsorbed or in surface-grafted form. Hydrogels are polymeric particles consisting of water-soluble polymer chains, chemically or physically connected using, in general, a cross-linking agent. These materials do not dissolve in water but may swell considerably in aqueous medium, demonstrating an extraordinary ability (>20%) to absorb water into the reticulated structure. Such features make these materials promising tools in the biomedical field, especially as controlled drug release systems. This chapter describes recent progress in the development and applications of polymeric nanostructured hydrogels, mainly in the context of biomedical devices. Additionally, it reports the significant advances in synthesis and characterization strategies of these materials. Special attention is devoted to smart or stimuli-responsive bionanogels, which mimic the property of living systems responding to environmental changes such as pH, temperature, light, pressure, electric field, chemicals, or ionic strength, or a combination of different stimuli. Consequently, these bionanogels offer an efficient solution to various biomedical limitations in the field of drug administration.

Thermally-sensitive and Biocompatible Poly(N-vinylcaprolactam): A Kinetic Study of Free Radical Polymerization in Ethanol

Using nuclear magnetic resonance (1H-NMR), a kinetic study on the polymerization of N-vinylcaprolactam (NVCL) was performed under different polymerization conditions. The homopolymers were synthesized by free radical polymerization in ethanol, and azobisisobutyronitrile (AIBN) and 3-mercaptopropionic acid were used as the initiator and chain transfer agent (CTA), respectively. Moreover, the effect of the monomer concentration, initiator concentration and polymerization temperature on the kinetics of the reaction was evaluated. The results revealed that the aforementioned parameters had a significant effect on the polymerization rate (Rp ): as the monomer and initiator concentration increased, an increase in Rp and the overall activation energy was observed. Poly(N-vinylcaprolactam) (PNVCL) is a thermoresponsive and biocompatible polymer that possesses a LCST (low critical solution temperature) near physiological temperature. Thermoresponsive polymers with low molar masses are useful for biomedical applications; thus, the effect of the molar mass on the polymerization rate and the LCST of PNVCL was studied. The number-average molar mass () and the polydispersity of the homopolymers were measured with a gel permeation chromatograph coupled to a triple detector (GPC/SEC/LALS), and the LCST of the PNVCL was determined by UV-visible analyses.

Synthesis and characterization of poly(N-vinylcaprolactam)-based spray-dried microparticles exhibiting temperature and pH-sensitive properties for controlled release of ketoprofen

Abstract Poly(N-vinylcaprolactam) (PNVCL) and poly(N-vinylcaprolactam-co-acrylic acid) (poly(NVCL-co-AA)) were synthesized by solution-free radical polymerization and displayed thermo-responsive behavior, with lower critical solution temperatures (LCSTs) of 35 °C and 39 °C, respectively. The incorporation of AA unities made the poly(NVCL-co-AA) sensitive to both pH and temperature. They were exploited in this work in preparing microparticles loaded with ketoprofen via spray-drying to modulate the drug release rate by changing pH or temperature. The interaction between polymer and drug was studied using X-ray diffractometry, Raman spectrometry and scanning electron microscopy (SEM). The biocompatibility of pure polymers, free ketoprofen as well as the spray-dried particles was demonstrated in vitro by low cytotoxicity and a lack of nitric oxide production in macrophages at concentrations as high as 100 µg/ml. The release profile of ketoprofen was evaluated by in vitro assays at different temperatures and pH values. Drug diffusion out of PNVCL’s hydrated polymer network is increased at temperatures below the LCST. However, when poly(NVCL-co-AA) was used as the matrix, the release of ketoprofen was primarily controlled by the pH of the medium. These results indicated that PNVCL and the novel poly(NVCL-co-AA) could be promising candidates for pH and temperature-responsive drug delivery systems.