Film-Forming Thermoresponsive Nanogels for Dermal Protein Delivery

VERÓNICA GONZALEZ; LUIS GUGLIOTTA; ANA S. SONZOGNI; ROQUE MINARI

Punta Cana

Congreso; Pólimer Reaction Engineering X; 2018

Thermoresponsive nanogels (NGs) have great potential as nanocarriers because of their high stability in aqueous solutions, elevated biocompatibility, high loading capacity, controlled release of an active component, fast response to temperature change, and design flexibility. In this scenario, a NG dispersion with a film forming ability could be useful for designing a dermal platform for drugs delivery, where the delivering film/patch could be previously obtained or directly formed onto the surface where the release is required. In this work a novel process was designed to synthesize thermoresponsive NGs with film-forming ability. This strategy pursues to synthesize N-vinylcaprolactam (VCL)-based nanogels with a separate phase composed of a random copolymer of VCL-butyl acrylate (BA) that promotes film formation by particle coalescence. The crosslinked poly(VCL) phase, which presents a transition temperature close to the body temperature (32-38°C), provides a reservoir to hold and transport drugs or biomacromolecules. NG dispersion and formed films were fully characterized by standard methods. The presence of both phases in the NGs was corroborated through DSC by observing two Tg corresponding to the crosslinked poly(VCL) and to a random copolymer of VCL-BA. Synthesized NG dispersions showed a minimum film formation temperature lower than 7 ºC, thus allowing film production below room temperature. Figure 1 shows a scheme of the film-forming process and two pictures corresponding to the obtained NG dispersion and the formed film. Also, films presented similar thermoresponsiveness than NGs dispersion (Figure 2). The NGs are well tolerated by human fibroblast, and were also able to load and efficiently release proteins (without modifying their secondary structure) in PBS. Finally, the film capability to release proteins through the skin was demonstrated, by an ovalbumin skin penetration study. These results indicate that the present proposal could be a good candidate for developing a dermal protein delivery platform.