ABSTRACT
Photodynamic therapy (PDT) is a medical treatment in which a combination of a photosensitizing drug and visible light produces highly cytotoxic reactive oxygen species (ROS) that leads to cell death. One of the main drawbacks of PDT for topical treatments is the limited skin penetration of some photosensitizers commonly used in this therapy. In this study, we propose the use of polymeric microneedles (MNs) prepared from silk fibroin and poly(vinyl alcohol) (PVA) to increase the penetration efficiency of porphyrin as possible applications in photodynamic therapy. The microneedle arrays were fabricated from mixtures in different proportions (1:0, 7:3, 1:1, 3:7, and 0:1) of silk fibroin and PVA solutions (7%); the polymer solutions were cast in polydimethylsiloxane (PDMS) molds and dried overnight. Patches containing grids of 10 × 10 microneedles with a square-based pyramidal shape were successfully produced through this approach. The polymer microneedle arrays showed good mechanical strength under compression force and sufficient insertion depth in both Parafilm M and excised porcine skin at different application forces (5, 20, 30, and 40 N) using a commercial applicator. We observe an increase in the cumulative permeation of 5-[4-(2-carboxyethanoyl) aminophenyl]-10,15,20-tris-(4-sulphonatophenyl) porphyrin trisodium through porcine skin treated with the polymer microneedles after 24 h. MNs may be a promising carrier for the transdermal delivery of photosensitizers for PDT, improving the permeation of photosensitizer molecules through the skin, thus improving the efficiency of this therapy for topical applications.
Subject(s)
Fibroins , Animals , Needles , Photosensitizing Agents , Polyvinyl Alcohol , Singlet Oxygen , SwineABSTRACT
Graphene nanoplatelets (GNP) and carbon nanotubes (CNT) are used to enhance electrical and mechanical properties of epoxy-based nanocomposites. Despite the evidence of synergetic effects in the hybrid GNP-CNT-epoxy system, there is still a lack of studies that focus on the influence of different dispersion methods on the final properties of these ternary systems. In the present work, direct and indirect ultrasonication methods were used to prepare single- and hybrid-filled GNP-CNT-epoxy nanocomposites, varying the amplitude and time of sonication in order to investigate their effect on electrical and thermomechanical properties. Impedance spectroscopy was combined with rheology and electron microscopy to show that high-power direct sonication tends to degrade electrical conductivity in GNP-CNT-epoxy nanocomposites due to damage caused in the nanoparticles. CNT-filled samples were mostly benefitted by low-power direct sonication, achieving an electrical conductivity of 1.3 × 10-3 S·m-1 at 0.25 wt.% loading, while indirect sonication was not able to properly disperse the CNTs and led to a conductivity of 1.6 ± 1.3 × 10-5. Conversely, specimens filled with 2.5 wt. % of GNP and processed by indirect sonication displayed an electrical conductivity that is up to 4 orders of magnitude higher than when processed by direct sonication, achieving 5.6 × 10-7 S·m-1. The introduction of GNP flakes improved the dispersion state and conductivity in hybrid specimens processed by indirect sonication, but at the same time impaired these properties for high-power direct sonication. It is argued that this contradictory effect is caused by a selective localization of shorter CNTs onto GNPs due to strong π-π interactions when direct sonication is used. Dynamic mechanical analysis showed that the addition of nanofillers improved epoxy's storage modulus by up to 84%, but this property is mostly insensitive to the different processing parameters. Decrease in crosslinking degree and presence of residual solvent confirmed by Fourier-transform infrared spectroscopy, however, diminished the glass transition temperature of the nanocomposites by up to 40% when compared to the neat resin due to plasticization effects.