Desenvolvimento de membranas inteligentes para liberação de fármacos com potencial para aplicação em tratamento de câncer de pele

Abstract

This work aimed to develop an intelligent membrane platform for controlled release with potential application in topical skin treatments, including cutaneous cancer. Gold nanoparticles (AuNPs) were synthesized via two routes: the Turkevich method (sodium citrate) and a green route (tannic acid). Both approaches successfully produced AuNPs, as confirmed by UV–Vis SPR bands in the 520–550 nm range (≈533 nm for citrate and ≈529 nm for tannic acid). Transmission electron microscopy (TEM) showed predominantly spherical, monodisperse nanoparticles, with mean diameters of 19.8 ± 2.34 nm (citrate) and 9.56 ± 2.66 nm (tannic acid). FTIR spectra indicated functional groups consistent with the reducing/stabilizing agents, revealing distinct surface chemistries between the two syntheses. In antimicrobial susceptibility assays, AuNPs showed no antibacterial activity under the tested conditions (2.5 µg/mL). In cell assays, tannic-acid-reduced AuNPs displayed higher biocompatibility (~85.89% viability), whereas citrate-derived AuNPs were more cytotoxic (~40.56% viability), supporting the selection of the green-route AuNPs for subsequent steps. The feasibility of microRNA functionalization was indicated by a shift in the SPR peak after conjugation. AuNPs were then encapsulated in PNIPAm, with indirect evidence from the attenuation/disappearance of the SPR band in UV–Vis spectra and confirmation by TEM, which revealed nanoparticle aggregates surrounded by a polymeric matrix; optimization studies were suggested to reduce aggregation. Thermoresponsive behavior assessed between 31 and 37 °C showed an increase in the plasmonic band with temperature and stabilization near 37 °C, consistent with PNIPAm responsiveness and relevant to physiological conditions. In parallel, poly(ε-caprolactone) (PCL) membranes were produced by electrospinning, yielding uniform fibers and good reproducibility. Ozone sterilization was effective (no microbial contamination) and preserved wettability (~123°), chemical composition (FTIR/Raman), thermal behavior (TGA/DSC), and mechanical performance. The membranes exhibited excellent biocompatibility with MRC-5 fibroblasts (>97% viability) and supported cell adhesion. Finally, PCL membranes incorporating PNIPAm(AuNP) by ex situ and in situ approaches were evaluated by UV–Vis at 37 °C, indicating progressive release; the in situ approach showed a more uniform profile. Overall, the PCL/PNIPAm(AuNP) system represents a promising platform for local delivery of drugs and biomolecules (including microRNAs), with potential applications in complex wound management and targeted therapies for cutaneous neoplasms.