Metronidazole-loaded gold nanoparticles in natural rubber latex as a potential wound dressing.

Gold nanoparticles (AuNPs) have shown interesting properties and specific biofunctions, providing benefits and new opportunities for controlled release systems. In this research, we demonstrated the use of natural rubber latex (NRL) from Hevea brasiliensis as a carrier of AuNPs and the antibiotic metronidazole (MET). We prepared AuNP-MET-NRL and characterized by physicochemical, biological and in vitro release assays. The effect of AuNPs on MET release was evaluated using UV-Vis and Laser-Induced Breakdown Spectroscopy (LIBS) techniques. AuNPs synthesized by Turkevich and Frens method resulted in a spherical shape with diameters of 34.8 ± 5.5 nm. We verified that there was no emergence or disappearance of new vibrational bands. Qualitatively and quantitatively, we showed that the MET crystals dispersed throughout the NRL. The Young's modulus and elongation values at dressing rupture were in the range appropriate for human skin application. 64.70% of the AuNP-MET complex was released within 100 h, exhibiting a second-order exponential release profile. The LIBS technique allowed monitoring of the AuNP release, indicating the Au emission peak reduction at 267.57 nm over time. Moreover, the dressing displayed an excellent hemocompatibility and fibroblast cell viability. These results demonstrated that the AuNP-MET-NRL wound dressing is a promising approach for dermal applications.

Human Mesenchymal Stem Cells Seeded on the Natural Membrane to Neurospheres for Cholinergic-like Neurons.

This study aimed to differentiate human mesenchymal stem cells (hMSCs) from the human umbilical cord in cholinergic-like neurons using a natural membrane. The isolation of hMSCs from Wharton's jelly (WJ) was carried out using "explant" and mononuclear cells by the density gradient from umbilical blood and characterized by flow cytometry. hMSCs were seeded in a natural functional biopolymer membrane to produce neurospheres. RT-PCR was performed on hMSCs and neurospheres derived from the umbilical cord. Neural precursor cells were subjected to a standard cholinergic-like neuron differentiation protocol. Dissociated neurospheres, neural precursor cells, and cholinergic-like neurons were characterized by immunocytochemistry. hMSCs were CD73+, CD90+, CD105+, CD34- and CD45- and demonstrated the trilineage differentiation. Neurospheres and their isolated cells were nestin-positive and expressed NESTIN, MAP2, ßIII-TUBULIN, GFAP genes. Neural precursor cells that were differentiated in cholinergic-like neurons expressed ßIII-TUBULIN protein and choline acetyltransferase enzyme. hMSCs seeded on the natural membrane can differentiate into neurospheres, obtaining neural precursor cells without growth factors or gene transfection before cholinergic phenotype differentiation.

Ibuprofen-loaded biocompatible latex membrane for drug release: Characterization and molecular modeling.

The incorporation of drugs and bioactive compounds in the natural rubber latex (NRL) matrix has been an alternative for the development of transdermal release membranes. Ibuprofen (IBF) is known to be used to treat inflammatory diseases, but when administered orally, high concentrations can cause some adverse problems. In this work, the incorporation of IBF in the NRL membranes was evaluated by physical-chemical, in vitro permeation, hemocompatibility and molecular modeling assays. In addition, the in vitro release profile of IBF in acid and basic media was analyzed during 96 h. The IBF-NRL membrane exhibited the absence of intermolecular bonding that could hinder drug release and presented compatible mechanical properties for applications as a cutaneous adhesive (0.58 and 1.12 MPa to Young's modulus and rupture tension, respectively). The IBF-NRL system did not present a significant hemolysis degree (1.67%) within 24 h. The release test indicated that in the first hours of the study, 48.5% IBF was released at basic pH and 22.5% at acidic pH, which is characteristic of a burst effect. Then, a stable release profile was observed until the end of the assay, with total IBF release of 60% in alkaline medium and 50% in acidic medium. The drug permeation results indicated that the IBF-NRL membranes can be used for the local skin treatment with permeation of 3.11% of IBF. Dynamic Molecular simulations indicated a pronounced electric dipole in the ionized form of IBF, which suggests a more effective interaction with water, explaining the efficient drug release in alkaline solutions. In general, the results demonstrate that the IBF-NRL membrane has great potential for a new adhesive that can be used for the treatment of inflammatory processes and injuries.

Gentamicin encapsulated within a biopolymer for the treatment of Staphylococcus aureus and Escherichia coli infected skin ulcers.

Skin wound infection requires carefully long-term treatment with an immense financial burden to healthcare systems worldwide. Various strategies such as drug delivery systems using polymer matrix from natural source have been used to enhance wound healing. Natural rubber latex (NRL) from Hevea brasiliensis has shown angiogenic and tissue repair properties. Gentamicin sulfate (GS) is a broad-spectrum antibiotic which inhibits the growth of a wide variety of microorganisms and, because of this, it has also been applied topically for treatment of local infections. The aim of this study was to develop a GS release system using NRL as matrix for Staphylococcus aureus and Escherichia coli infected skin ulcers treatment, without changing drug antibiotic properties. The matrix did not change the GS antimicrobial activity against S. aureus and E. coli strains. Moreover, the NRL-GS biomembrane did not exhibit hemolytic activity, being non-toxic to red blood cells. The eluates of NRL-GS biomembranes and GS solutions did not significantly reduce the survival of Caenorhabditis elegans worms for 24 h at any of the tested concentrations. Thus, these results emphasize that the NRL-GS biomembrane proved to be a promising biomaterial for future studies on the development of dressings for topical uses, inexpensive and practicable, keeping drug antibiotic properties against pathogens and to reduce the side effects.

Novel polymeric dressing to the treatment of infected chronic wound.

Natural rubber latex (NRL) is a natural polymer which has arisen large interest in the biomedical field, mostly, due to its ability to facilitate angiogenesis and therefore, tissue repair. Moxifloxacin (MXF) is a broad-spectrum antibiotic orally administrated. Considering the biological properties of the NRL and its ability to deliver a wide range of compounds, the present study aimed to develop a novel device for infected chronic wound treatment. MXF-loaded NRL was obtained by a casting method. The results demonstrated that the incorporation of MXF in NRL did not promote any molecular interaction, preserving the integrity of the compounds. The mechanical properties of the biomaterial did not show any significant change, indicating enough elasticity for dermal application. The microbiological assays confirmed the ability of the polymer to deliver the drug without influencing its pharmacological properties. Moreover, it has expressed activity against major bacterial strains presented in wound infections. Finally, the biomaterial shown biocompatibility from the in vitro study. Thus, the present work has shown that MXF-loaded NRL membrane is a promising biomaterial to infected wound treatment.

Natural rubber latex membranes incorporated with three different types of propolis: Physical-chemistry and antimicrobial behaviours.

Natural Rubber Latex (NRL) is a biocompatible material with demonstrated capacity to induce vascularisation and tissue regeneration. Propolis is a complex resinous product prepared by Apis mellifera with the aim of protecting beehives against infectious microorganisms. It is flora-dependent and its antimicrobial activity can vary according to its geographical origin. This study compares the incorporation of three different types of propolis into an NRL membrane aiming at optimal controlled release of propolis potential antimicrobial compounds towards Candida albicans whilst keeping NRL mechanical characteristics desirable for wound healing bandage purposes. The propolis samples were classified as red, green and poplar propolis according to their chemical composition determined by ultra-high performance liquid chromatography coupled in series with both UV spectrophotometry and high-resolution mass spectrometry. The Minimum Inhibitory Concentrations (MIC) towards C. albicans were determined before their incorporation into NRL membranes. The release of NRL-propolis components in Simulated Body Fluid (SBF) was monitored by UV-Vis spectroscopy. The antimicrobial activity and the effects of the materials released on mouse fibroblasts were assessed. FTIR analyses were carried out in order to verify the formation of new chemical bonds that might prevent the release of propolis components from the NRL membrane. The mechanical characteristics of the NRL membranes remained adequate after the incorporation of the three types of propolis investigated whilst allowing the release of the red, and poplar propolis most active compounds against C. albicans. At 30 and 50% the released materials (eluates) from the NRL membranes incorporated with red and poplar propolis types were not toxic to fibroblast cells. These results suggest that red and poplar propolis can be incorporated into NRL membranes for the preparation of wound healing dressing.

Natural latex-glycerol dressing to reduce nipple pain and healing the skin in breastfeeding women.

BACKGROUND: Nipple pain is the second most common reason for early weaning, exceeded only by the insufficient milk supply. Nipple fissures can bring other problems, acting also as a portal for bacteria and leading to mastitis. This work proposes the breast protector composite development using materials with tissue repair and moisturizing properties, aligned with a low-cost procedure, aiming not only to relieve pain, but also to heal the nipple fissures caused by breastfeeding. MATERIALS AND METHODS: For the dressings, production was used Natural Latex extracted from the rubber tree and glycerol. The Samples were evaluated chemically and physically by the techniques of Scanning Electron Microscopy, Fourier transform infrared spectroscopy, mechanical traction, and contact angle. The samples were also biologically evaluated by the hemolytic and cytotoxic activity assays. RESULTS: From the physical-chemical assays, the matrix with glycerol has high pore density; the natural latex and glycerol do not covalently interact, indicating that the glycerol can be released; the glycerol addition makes the matrix more elastic but fragile, and increase the wettability. From the biological assays, both materials showed no hemolytic effects; and the cytotoxicity results showed that glycerol did not present cytotoxicity in the fibroblasts, but show a dose-dependent influence in the keratinocytes. CONCLUSION: The material developed for application in breast fissures has mechanical properties similar to those found for materials for dermal applications, present high wettability and pore density. Furthermore, the material showed no cytolytic activity and the tests with skin cell cultures demonstrated the biocompatibility.

Natural rubber latex coated with calcium phosphate for biomedical application.

Natural rubber latex (NRL) is a flexible biomembrane that possesses angiogenic properties and has recently been used for guided bone regeneration, enhancing healing without fibrous tissue, allergies or rejection. Calcium phosphate (Ca/P) ceramics have chemical, biological, and mechanical properties similar to mineral phase of bone, and ability to bond to the host tissue, although it can disperse from where it is applied. Therefore, to create a composite that could enhance the properties of both materials, NRL biomembranes were coated with Ca/P. NRL biomembranes were soaked in 1.5 times concentrated SBF solution for seven days, avoiding the use of high temperatures. SEM showed that Ca/P has been coated in NRL biomembrane, XRD showed low crystallinity and FTIR showed that is the carbonated type B. Furthermore, hemolysis of erythrocytes, quantified spectrophotometrically using materials (Ca/P, NRL, and NRL + Ca/P) showed no hemolytic effects up to 0.125 mg/mL (compounds and mixtures), indicating no detectable disturbance of the red blood cell membranes. The results show that the biomimetic is an appropriate method to coat NRL with Ca/P without using high temperatures, aiming a new biomembrane to improve guided bone regeneration.

Novel sustained-release of Stryphnodendron obovatum leaves extract using natural rubber latex as carrier

Natural rubber latex biomembranes (NRL), obtained from rubber tree Hevea brasiliensis (Willd. ex A. Juss.) Mull. Arg., have been used as sustained drug release of drugs and plant extracts with medicinal properties. The Stryphnodendron obovatum Bench (Fabaceae), popularly known as "barbatimão" has anti-inflammatory and healing properties already described in literature. Thus, the aim of this work were to study the release behavior of the hydroethanolic extract from the leaves of S. obovatum loaded in the NRL by ultraviolet­visible spectroscopy (UV-VIS). The release followed a biexponential pattern and the mechanism of release was Super Case II (n > 1). FTIR analyses did not show reaction between NRL and extract, only intermolecular interaction. From SEM was possible to observe the extract at the surface, responsible for the initial fast release, which the concentrations at 5.0 mg/mL released 2.4% and at 0.1 mg/mL released 96.8%; both reached the plateau in 7 days.