Tuning the properties of carboxymethylchitosan-based porous membranes for potential application as wound dressing.

Wound repair is a complex process that calls for strategies to allow a rapid and effective regeneration of injured skin, which has stimulated the research of advanced wound dressings. Herein, highly porous membranes of N,O-carboxymethylchitosan (CMCh), and poly (vinyl alcohol) (PVA) were successfully prepared via a green and facile freeze-drying method of blend solutions containing CMCh/PVA at weight ratio 25/75. Membranes composed only by CMCh were also prepared and genipin was used for crosslinking. Different contents of TiO2 nanoparticles were incorporated to both type of membranes, which were characterized in terms of morphology, porosity (Φ), swelling capacity (S.C.), mechanical properties, susceptibility to lysozyme degradation and in vitro cytotoxicity toward human fibroblast (HDFn) and keratinocytes (HaCaT) cells. Larger apparent pores were observed in the surface of the genipin-crosslinked CMCh membrane, which resulted in higher porosity (Φ ≈ 76%) and swelling capacity (S.C. ≈ 1720%) as compared to CMCh/PVA membrane (Φ ≈ 68%; S.C. ≈ 1660%). The porosity of both types of membranes decreased upon the addition of TiO2 nanoparticles while swelling capacity increased. Due to their high porosity and swelling capacity, adequate mechanical properties, controlled degradability, and cytocompatibility, such carboxymethylchitosan-based membranes are potentially useful as wound dressings.

MAL-associated methyl nicotinate for topical PDT improvement.

Photosensitization of all tissue in sufficient quantity to generate damage is one of the limiting factors for Photodynamic Therapy (PDT) efficiency. Methyl nicotinate (MN) is a thermogenic and vasodilating substance that facilitates the topical tissue penetration of some compounds. The topical MAL (methyl aminolevulinate) PDT is commonly used as a precursor of protoporphyrin IX (PpIX). This study investigates the safety of topical use in NM, as well as its ability to improve the efficiency of topical PDT. For this, we investigate the cytotoxicity of MN, as well as its actions in increasing cellular metabolism and vasodilation. Besides, its ability to optimize the formation of PpIX in the tissue when associated with MAL cream was investigated, besides assessing the severity of necrosis obtained by treatments. The cytotoxicity of MN was tested for concentrations of 0, 0.1, 0.25, 0.5, 0.75 and 1% in cell culture. For the concentration of 0.5%, the cellular metabolism was evaluated using confocal microscopy to calculate the redox rate. In the Chorioallantoic Membrane Model, vasodilation was evaluated for concentrations of 0.5 and 1% MN during 1 h of incubation. In the animal model, the healthy skin of Wistar rat was used to evaluate the production of PpIX in the tissue and the degree of necrosis obtained by Photodynamic therapy when using NM associated with methyl aminolevulinate. It was observed the non-cytotoxicity in vitro of MN in the concentration used (0.5%) and its ability to increase cellular metabolism. In a chorioallantoic model, the MN vasodilation power was demonstrated for different caliber of vessels. In vivo studies are showing that the incorporation of MN in the MAL cream increases the amount of PpIX produced in the tissue causing a higher effect on the epidermis after PDT. This improvement of the protocol may make the procedure more effective both in the destruction of tumor tissue and in the treatment of deeper cells decreasing possible recurrence, in addition to allowing improvements in the protocol, such as reducing the cream's incubation time.

Luminescent nanohybrids based on silica and silylated Ru(II)-Yb(III) heterobinuclear complex: new tools for biological media analysis.

Lanthanide (Ln) complexes emitting in the near-infrared (NIR) region have fostered great interest as upcoming optical tags owing to their high spatial and temporal resolution emission as well deeper light penetration in biological tissues for non-invasive monitoring. For use in live-cell imaging, lanthanide complexes with long-wavelength absorption and good brightness are especially critical. Light-harvesting ligands of Ln complexes are typically excited in the ultraviolet region, which in turn trigger simultaneously autofluorescence and long-exposition damage of living systems. The association of d-metalloligands rather than organic chromophores enables the excitation of NIR-emitting Ln complex occurs in the visible region. Taking advantage of the long-lived excited states and intense absorption band in the ultraviolet (UV) to NIR region of Ru(II), we successfully design a dual-emitting (in the visible and NIR region) d-f heterobinuclear complex based on Ru(II) metalloligand and Yb(III) complex. In addition, we developed luminescent nanohybrids by grafting of Ru(II)-Yb(III) heterobinuclear complexes containing silylated ligands on the surface of mesoporous and dense silica matrix. The nanomarkers were successfully applied for imaging of murine melanoma B16-F10 and neonatal human dermal fibroblast HDFn cell cultures by one-photon or two-photon absorption using laser scanning confocal microscopy. Great cellular uptake, low cytotoxicity and the possibility to achieve visible and NIR emission via two-photons excitation show that the nanohybrids are remarkable markers for in vitro and a potential tool for in vivo applications.

Graphene Oxide Mediated Broad-Spectrum Antibacterial Based on Bimodal Action of Photodynamic and Photothermal Effects.

Graphene oxide (GO) with their interesting properties including thermal and electrical conductivity and antibacterial characteristics have many promising applications in medicine. The prevalence of resistant bacteria is considered a public health problem worldwide, herein, GO has been used as a broad spectrum selective antibacterial agent based on the photothermal therapy (PTT)/photodynamic therapy (PDT) effect. The preparation, characterization, determination of photophysical properties of two different sizes of GO is described. In vitro light dose and concentration-dependent studies were performed using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria based on the PTT/PDT effect used ultra-low doses (65 mW cm-2) of 630 nm light, to achieve efficient bacterial decontamination. The results show that GO and nanographene oxide (nGO) can sensitize the formation of 1O2 and allow a temperature rise of 55°C to 60°C together nGO and GO to exert combined PTT/PDT effect in the disinfection of gram-positive S. aureus and gram-negative E. coli bacteria. A complete elimination of S. aureus and E. coli bacteria based on GO and nGO is obtained by using a dose of 43-47 J cm-2 for high concentration used in this study, and a dose of around 70 J cm-2 for low dose of GO and nGO. The presence of high concentrations of GO allows the bacterial population of S. aureus and E. coli to be more sensitive to the use of PDT/PTT and the efficiency of S. aureus and E. coli bacteria disinfection in the presence of GO is similar to that of nGO. In human neonatal dermal fibroblast, HDFs, no significant alteration to cell viability was promoted by GO, but in nGO is observed a mild damage in the HDFs cells independent of nGO concentration and light exposure. The unique properties of GO and nGO may be useful for the clinical treatment of disinfection of broad-spectrum antimicrobials. The antibacterial results of PTT and PDT using GO in gram-positive and gram-negative bacteria, using low dose light, allow us to conclude that GO and nGO can be used in dermatologic infections, since the effect on human dermal fibroblasts of this treatment is low compared to the antibacterial effect.

Nanostructured electrospun nonwovens of poly(ε-caprolactone)/quaternized chitosan for potential biomedical applications.

Blend solutions of poly(ε-caprolactone) (PCL) and N-(2-hydroxy)-propyl-3-trimethylammonium chitosan chloride (QCh) were successfully electrospun. The weight ratio PCL/QCh ranged in the interval 95/5-70/30 while two QCh samples were used, namely QCh1 (DQ¯â€¯= 47.3%; DPv¯â€¯= 2218) and QCh2 (DQ¯â€¯= 71.1%; DPv¯â€¯= 1427). According to the characteristics of QCh derivative and to the QCh content on the resulting PCL/QCh nonwoven, the nanofibers displayed different average diameter (175 nm-415 nm), and the nonwovens exhibited variable porosity (57.0%-81.6%), swelling capacity (175%-425%) and water vapor transmission rate (1600 g m-2 24 h-2500 g m-2 24 h). The surface hydrophilicity of nonwovens increases with increasing QCh content, favoring fibroblast (HDFn) adhesion and spreading. Tensile tests revealed that the nonwovens present a good balance between elasticity and strength under both dry and hydrated state. Results indicate that the PCL/QCh electrospun nonwovens are new nanofibers-based biomaterials potentially useful as wound dressings.