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Quantification of voriconazole (VCZ) by visible spectrophotometry based on the VCZ-induced reduction of thionine (red) to leucothionine (colorless) under alkaline conditions.

Pigments are among the most fascinating molecules found in nature and used by human civilizations since the prehistoric ages. Although most of the bio-dyes reported in the literature were discovered around the eighties, the necessity to explore novel compounds for new biological applications has made them resurface as potential alternatives. Prodigiosin (PG) is an alkaloid red bio-dye produced by diverse microorganisms and composed of a linear tripyrrole chemical structure. PG emerges as a really interesting tool since it shows a wide spectrum of biological activities, such as antibacterial, antifungal, algicidal, anti-Chagas, antiamoebic, antimalarial, anticancer, antiparasitic, antiviral, and/or immunosuppressive. However, PG vehiculation into different delivery systems has been proposed since possesses low bioavailability because of its high hydrophobic character (XLogP3-AA = 4.5). In the present review, the general aspects of the PG correlated with synthesis, production process, and biological activities are reported. Besides, some of the most relevant PG delivery systems described in the literature, as well as novel unexplored applications to potentiate its biological activity in biomedical applications, are proposed., Centro de Investigación y Desarrollo en Fermentaciones Industriales, Instituto de Investigaciones Bioquímicas de La Plata

Nitric oxide (NO) is an important endogenous molecule that plays several roles in biological systems. NO is synthesized in human skin by three isoforms of nitric oxide synthase (NOS) and, depending on the produced NO concentration, it can actuate in wound healing, dermal vasodilation, or skin defense against different pathogens, for example. Besides being endogenously produced, NO-based pharmacological formulations have been developed for dermatological applications targeting diverse pathologies such as bacterial infection, wound healing, leishmaniasis, and even esthetic issues such as acne and skin aging. Recent strategies focus mainly on developing smart NO-releasing nanomaterials/biomaterials, as they enable a sustained and targeted NO release, promoting an improved therapeutic effect. This review aims to overview and discuss the main mechanisms of NO in human skin, the recent progress in the field of dermatological formulations containing NO, and their application in several skin diseases, highlighting promising advances and future perspectives in the field.

Every year the incidence of cancer and the death rate are increasing worldwide. The drug 8-hydroxyquinoline platinum(II) [PtCl(8-O-quinoline)(dmso)] (8HQ-Pt) has been identified as a promising antitumor complex. Nanostructured lipid carriers (NLC) are second-generation drug nanocarrier systems that have superior advantages over other kinds of colloidal carrier systems. 8HQ-Pt compound loaded NLC formulations of cetyl esters (SS) were synthesized via ultrasonication in the presence of two different liquid oils: capric triglyceride, or olive oil. The physicochemical and microscopic characterizations of NLC were analyzed via dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray diffraction analysis (XRD). In vitro drug release and cytotoxicity, cell uptake and apoptosis assays against the human colon cancer cell line HT-29 were investigated. The results showed that NLCs indicated a narrow size distribution and a mean particle diameter in the range of 136–159 nm. The thermal characteristic analysis confirmed the stability of NLCs up to 185 °C. Encapsulation efficiencies of the 8HQ-Pt compound in NLCs were about 80% and the 8HQ-Pt compound in the formulations showed a controlled release profile during 72 h. The release profiles of these two different formulations and the antitumor effect on the HT-29 cell line were compared with those of the free 8HQ-Pt compound. The cellular uptake of two different NLC groups was proved by fluorescence microscopy and the presence of capric triglyceride liquid oil in the formulation increased the intracellular drug delivery capacity when compared with olive oil.

In the global context of emerging pathogens associated with respiratory diseases, novel nanostructured lipid carriers (NLCs) having both antioxidant and antimicrobial properties produced by α-tocopherol (αT) and levofloxacin (LV), respectively, were developed. The hybrid NLCs were made of solid lipid esters and liquid αT as the central core, plus chitosan (Chi) and poloxamer 188 as surface stabilizers. Three formulations were rationally designed considering lipids with different physicochemical properties: cetyl ester (SS), glyceryl dibehenate (CO) and glyceryl tristearate (DY). The properties and stability of the nanoformulations were studied by dynamic light scattering considering the effects of the homogenization time, surfactant concentration, and initial lipid amount on the mean size, polydispersity index (PDI) and zeta potential of the nanoparticles. The effect of αT on the nanostructuration of the lipid matrix was demonstrated by X-ray diffraction, differential scanning calorimetry, and thermogravimetry analysis. The potential ability of the NLCs to interact with the mucosa was studied by rheological methods, demonstrating a reduction in mucin cohesiveness and elasticity due to the mucoadhesive properties of NLCs coated with chitosan. Solid lipid nanoparticles (SLNs) of SS, CO and DY encapsulated 58.0 ± 3.2, 25.7 ± 7.1, and 27.9 ± 1.5% LV, respectively, while the NLC formulations were able to encapsulate 80–90% LV and allowed controlled release of the drug. The enhanced antimicrobial properties of the SLNs/NLCs against Pseudomonas aeruginosa and Staphylococcus aureus were confirmed. The presence of αT in the formulations provided the antioxidant properties of the NLCs. Finally, no acute toxicities of the formulations were observed in two human lung cell lines (A549 and Calu-3).

Biopolymeric blends based on bacterial cellulose (BC) films modified with low molecular weight chitosan (Chi) were developed for controlled release of ciprofloxacin (Cip). Biophysical studies revealed a compatible and cooperative network between BC and Chi including deep structural changes in the BC matrix shown by spectroscopic and thermal analyses (SEM, roughness analysis, FTIR, XRD, TGA, mechanical properties and water vapor transmission rate). Incorporation of chitosan to BC matrix generated a thickening scaffold with high permeability to water vapor from 0.7 to 3.2 g mm/m2 h. Cip loaded onto the BC-Chi film showed a hyperbolic release profile with a 30% decrease in antibiotic release mediated by the presence of Chi. BC-Chi blend films containing Cip tested against Pseudomonas aeruginosa and Staphylococcus aureus showed a synergic effect of chitosan on Cip antimicrobial activity. Besides, in vitro studies revealed the lack of cytotoxicity of BC-Chi-Cip films in human fibroblasts.

Nanoparticles composed of solid lipids and their hybrid formulations containing polymers, peptides, proteins, and inorganic compounds are valuable materials for the future development of therapeutic devices. Hybrid lipid carriers are multipurpose, and they can be formulated for the delivery of hydrophobic as well as hydrophilic drugs. Among their main advantages are high payload and stability, established controlled release kinetics, easy targeting, simple production and scale-up, a wide range of administration routes.

Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment. However, VitE is poorly soluble in aqueous environments. Here, VitE encapsulation into solid lipid nanoparticles (SLN) composed of myristil myristate to improve its bioavailability was proposed. A 99.9 ± 0.1% encapsulation efficiency with a drug/lipid ratio of 500 µg/mg and 478 higher VitE solubility was obtained. The antioxidant properties of VitE after encapsulation were maintained. SLN-VitE showed a 228.2 nm mean diameter with low polidispersitivity (0.335), and negative Z potential (ζ ≈ -9.0 mV). The SLN were well-dispersed, displayed spherical and homogeneous morphology by TEM. A controlled release of VitE from SLN was found. The XRD and FTIR analyses revealed the presence of a nanostructured architecture of SLN after VitE incorporation. We probed the safety of SLN-VitE after contact with three in vitro cell models: erythrocytes, lymphocytes and HepG2 cells. The cell viability in presence of SLN, SLN-VitE, and their combinations with iron was not affected. The comet assay demonstrated that the DNA damage caused by iron administration was decrease in presence of SLN-VitE.

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein’s action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries., Centro de Investigación y Desarrollo en Fermentaciones Industriales

Candida auris, which is one of the causative agents of candidiasis, has been detected in several individuals with immune deficiency worldwide, mainly in different American countries, since 2012. C. auris infections are at risk of becoming epidemic because this species shows multi-drug resistance to several antifungal drugs available in the market; thus, since the current public health condition at global scale is threatened by the SARS-CoV-2 pandemic, C. auris infections could lead to high mortality rates. Different strategies, such as drug repurposing and the combination of antifungal drugs to other biocide molecules, were developed. However, they are time-limited strategies since drug resistance has increased due to C. auris pathologies. As an alternative, the recent development of nanotechnological devices has opened room for the efficient treatment of C. auris infections. Most specifically, the biocide effect of nanoparticles combined to/capped with antifungal drugs in different platforms seems to be an affordable technology to stop invasive C. auris infections.

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein's action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.

Lipid nanoparticles are so far among the most successful nanodelivery systems, considering the significant proportion of marketed nanocarriers that correspond to this category. High loading capacity, biocompatibility, and environmentally friendly obtention techniques can be mentioned among their most prominent specific advantages. The current research topic on Lipid Nanoparticles as a Novel Strategy to Deliver Bioactive Molecules encompasses original and review articles on a wide range of lipid nanoparticle-related topics, from encapsulation of gene therapies to novel characterization approaches. The collection of articles also expresses the increasing versatility of these nanosystems, owing to the use of hybrid and functionalized carriers., Facultad de Ciencias Exactas, Laboratorio de Investigación y Desarrollo de Bioactivos, Centro de Investigación y Desarrollo en Fermentaciones Industriales

The widespread and increased use of silver nanoparticles (AgNPs) as antimicrobial, antifungal, and antiviral agents results in an unknown release and accumulation into the aquatic environment and consequently in the trophic chain. In this chapter, different methods for AgNP synthesis, use, and applications; environmental concentration; potential mechanisms of toxicity; and the involved physicochemical factors are discussed. Also, the chapter provides an overview of the toxicity effects on key components of aquatic ecosystems: microalgae, plants, freshwater invertebrates, and fish. Final remarks aim to contribute to a better understanding of how this emerging pollutant may pose a risk in the immediate to long term to aquatic environments.

Nanotechnology has recently emerged as a promising tool in biomedicine research. An important branch of nanotechnology is drug delivery (DD) and drug targeting using a wide range of biomaterials with promising potential applications in many diseases. The aim of this chapter is to provide an overview of the evolution of nanotechnology in controlled pulmonary DD, exemplified by the myriad of applications in cancer, infectious diseases, asthma, and chronic pulmonary disease. Particular attention will be focused on the formulation strategies for improving systemic bioavailability of inhaled drugs and macromolecules, the formulation strategies for improving local targeting in the lung (airways versus alveoli), the formulation strategies for delivering drug and macromolecules, including siRNA and DNA into cells, and the formulation strategies with improved dose consistency. Recent nanoformulations and the biomaterials that are under investigation for controlled pulmonary DD, including preclinical and clinical studies, are included in this chapter.

Bacterial cellulose (BC) is a natural polymer that has fascinating attributes, such as biocompatibility, low cost, and ease of processing, being considered a very interesting biomaterial due to its options for moldability and combination. Thus, BC-based compounds (for example, BC/collagen, BC/gelatin, BC/fibroin, BC/chitosan, etc.) have improved properties and/or functionality, allowing for various biomedical applications, such as artificial blood vessels and microvessels, artificial skin, and wounds dressing among others. Despite the wide applicability in biomedicine and tissue engineering, there is a lack of updated scientific reports on applications related to dentistry, since BC has great potential for this. It has been used mainly in the regeneration of periodontal tissue, surgical dressings, intraoral wounds, and also in the regeneration of pulp tissue. This review describes the properties and advantages of some BC studies focused on dental and oral applications, including the design of implants, scaffolds, and wound-dressing materials, as well as carriers for drug delivery in dentistry. Aligned to the current trends and biotechnology evolutions, BC-based nanocomposites offer a great field to be explored and other novel features can be expected in relation to oral and bone tissue repair in the near future., Facultad de Ciencias Exactas

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.

Enzymes exhibit a tremendous potential due to the catalytic activity in response to physiological conditions and specific microenvironments. Exploiting these properties in combination with the versatility of biopolymers, a fascinating field for the rational development of a new class of "smart" delivery systems for therapeutic molecules is proposed. Many strategies have been recently developed to produce matrices with the desirable properties of molecular release, and enzymes could be playing a relevant role in modify the chemical composition of the polymers, the porosity and surface area of the matrices and modulate the kinetic of controlled release. Enzyme based computational systems have appeared as a relevant complementary tool to design novel smart bioactive matrices for programmable drug delivery. The present review is reporting the recent advances and projections of smart biopolymeric matrices activated by enzymes for sustained release of therapeutic molecules, highlighting various applications in the area of advanced drug delivery.

The discovery of new alternatives for the treatment of infectious diseases has become the focus of burgeoning global interest. The complexation of the wide-spectrum antibiotic nalidixic acid (NA) with oxidovanadium(IV) ion and its incorporation into hybrid nanoparticulate systems were explored. The V-NA complex proved to be a stronger antimicrobial agent against E. coli, B. cereus, S. aureus and P. aeruginosa than NA, based on inhibition experiments. Myristyl myristate nanostructured lipid carriers (NLCs) and polymeric nanoparticles of Eudragit NE30D (EuNPs) were hybridized with chitosan (chi) to increase their stability and mucoadhesivity. They showed V-NA encapsulation of 97.8 ± 0.5% and 96.1 ± 0.1% respectively. TEM and DLS characterization ascertained the presence of spherical positive charged NPs ranging from 170 to 330 nm. Controlled release of V-NA from NPs was observed with 30–40% release in 3 days. A considerable potentiation of V-NA antimicrobial activity from 5 to 10 times was elucidated against P. aeruginosa with MIC values of 59.3 and 129.9 μM for NLC/chi and EuNPs/chi respectively, in comparison with 625 μM of the free complex. Hybrid NPs were able to interfere with the quorum sensing of the reporter Chromobacterium violaceum. Cytotoxicity on mouse fibroblast L929 cells was evaluated in the range of 29.7–519 μM by MTT assay showing that, NLC/chi particles supported cell growth in the range of at 29.7–60 μM while Eu/chi do not exert cytotoxicity between 29.7 and 120 μM. These results suggest that nanoparticles are suitable systems for drug delivery applications.

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic. However, violacein is insoluble under physiological conditions preventing its potential therapeutic uses. Surface-active ionic liquids (SAILs) based on the cation 1-alkylimidazolium ([C

Violacein (Viol) is a pigment produced by several Gram-negative bacteria with many bioactivities, such as anticancer, virucide, and antiparasitic. However, violacein is insoluble under physiological conditions preventing its potential therapeutic uses. Surface-active ionic liquids (SAILs) based on the cation 1-alkylimidazolium ([CnHim]) with n = 10 to 16 alkyl carbon side chain lengths and acetate, bromide, methanesulfonate (S) or trifluoroacetate (F) as counterions were synthesized and screened to dissolve Viol in micellar aqueous media and for toxicological studies on the human lung carcinoma A549 cell line. Screening allowed the selection of 1.5 × 10−3% (w/v) [C16Him]-S because it combines low cytotoxicity with 71.5% cell viability and good interaction with 95.2% of the violacein kept in micellar solution for at least 48 h. [Viol-([C16Him]-S)] complex was used to develop an efficient hybrid solid lipid nanoparticle (SLN) carrier based on myristyl myristate and poloxamer 188 and tailored with folate to target cancer cells. Cellular SLN uptake was evaluated with fluorescent DiOC18 on A549, HCT-116, and HeLa cell lines expressing or not the folate receptor. The results showed fivefold incorporation of Viol nanoparticles in HCT-116 and HeLa cell cultures, displaying a high level of folate receptor. Biophysical characterization of the hybrid solid lipid carrier containing Viol was performed by dynamic light scattering, Fourier transform infrared, X-ray diffraction and X-ray photoelectron spectroscopies, and by transmission electron and cryo-transmission microscopies., Centro de Investigación y Desarrollo en Fermentaciones Industriales, Instituto de Investigaciones Bioquímicas de La Plata

In this study, the culture conditions necessary for the effective production of kefiran, using whey as a substrate, were evaluated through the one-factor-at-a-time and central-composite design methods. Using the optimal factors (whey supplemented with 15% (w/v) glucose fermented at 30 °C for 10 h without shaking), 0.20 g L−1 h−1 kefir grains composed of 18.57% (w/w) kefiran was obtained. The resulting polysaccharide was analyzed by high-pressure size-exclusion chromatography, gas chromatography-mass spectrometry, nuclear magnetic resonance, Fourier-transform infrared and Raman spectroscopy. Altogether, the results indicated that the purified polymer was homogenous and composed of galactose and glucose. The biocidal properties of the resulting kefiran were assessed, for the first time, using Live/Dead BacLight® real-time analysis, which indicated antimicrobial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium strains. Additionally, the kefiran, when applied to various S. typhimurium strains, showed diverse biocidal results when in the presence of antibiotic multiresistance markers. In summary, these results demonstrated that kefiran can be produced from whey-supplemented media with high productivity and without losing its structural or biocidal properties. Fil: Blandón, Lina M.. Universidade Federal do Paraná; Brasil Fil: Noseda, Miguel D.. Universidade Federal do Paraná; Brasil Fil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Melo Pereira, Gilberto Vinícius de. Universidade Federal do Paraná; Brasil Fil: Thomaz Soccol, Vanete. Universidade Federal do Paraná; Brasil Fil: Soccol, Carlos R.. Universidade Federal do Paraná; Brasil

In situ self-assembly stereo-specific synthesis of silver phosphate (AgP) microparticles (MPs) in one side bacterial cellulose (BC) membrane surface and loading of ciprofloxacin provides BC scaffolds with a broad-spectrum antimicrobial activity against Escherichia coli and Staphylococcus aureus. The BC membranes containing AgP-MPs can be loaded >5 times with ciprofloxacin compared to naked BC. The reuse of ciprofloxacin-loaded AgP-BC scaffolds in fresh cultures of both tested microbes showed high inhibition haloes without any signal of microbial resistance or scaffold activity decay after 30 days of assays. Additionally, microbial biofilms of E. coli and S. aureus were mostly killed by AgP-BC scaffolds loaded with ciprofloxacin in 1 h. The biophysical characterization of the hybrid AgP-BC scaffolds was performed by scanning electron microscopy (SEM), vibrational spectroscopy (FTIR), calorimetric techniques and X-ray diffraction (XRD). SEM images display AgP-MP spheroid structures with a high homogenous distribution on BC scaffold surfaces. The properties of the novel AgP-BC matrices are very promissory for biomedical applications, like a therapeutic dressing patches for the prevention and treatment of microbial infections in skin wounds and burns. Fil: Bayón, Bernardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Cacicedo, Maximiliano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina Fil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentina Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina