Psidium guajava L. phenolic compound-reinforced lamellar scaffold for tracheal tissue engineering.

The aim of this work was to develop a dense lamellar scaffold, as a biomimetic material with potential applications in the regeneration of tracheal tissue after surgical tumor resection. The scaffolds were produced by plastic compression technique, exploiting the use of total phenolic compounds (TPC) from Psidium guajava Linn as a potential cross-linking agent in a polymeric mixture based on collagen (COL), silk fibroin (SF), and polyethylene glycol 400 (PEG 400). Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) confirmed the chemical interactions between the polymers and the cross-linking of TPC between COL and SF. Morphological analyses showed scaffolds with porosity, interconnectivity, and a porous surface structure with a gyroid-like geometry. The analysis of the anisotropic degree resulted in anisotropic structures (0.1% TFC and 0.3% TFC) and an isotropic structure (0.5% TFC). In the mechanical properties, it was evidenced greater resistance for the 0.3% TFC formulation. The addition of TPC percentages did not result in a significant difference (p > 0.05) in swelling capacity and disintegration rate. The results confirmed that TPC were able to modulate the morphological, morphometric, and mechanical properties of scaffolds. Thus, this study describes a potential new material to improve the regeneration of major tracheal structures after surgical tumor removal.

Curcumin encapsulation in nanostructures for cancer therapy: A 10-year overview.

Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages.

Cachexia: Pathophysiology and Ghrelin Liposomes for Nose-to-Brain Delivery.

Cachexia, a severe multifactorial condition that is underestimated and unrecognized in patients, is characterized by continuous muscle mass loss that leads to progressive functional impairment, while nutritional support cannot completely reverse this clinical condition. There is a strong need for more effective and targeted therapies for cachexia patients. There is a need for drugs that act on cachexia as a distinct and treatable condition to prevent or reverse excess catabolism and inflammation. Due to ghrelin properties, it has been studied in the cachexia and other treatments in a growing number of works. However, in the body, exogenous ghrelin is subject to very rapid degradation. In this context, the intranasal release of ghrelin-loaded liposomes to cross the blood-brain barrier and the release of the drug into the central nervous system may be a promising alternative to improve its bioavailability. The administration of nose-to-brain liposomes for the management of cachexia was addressed only in a limited number of published works. This review focuses on the discussion of the pathophysiology of cachexia, synthesis and physiological effects of ghrelin and the potential treatment of the diseased using ghrelin-loaded liposomes through the nose-to-brain route.

Properties, Extraction Methods, and Delivery Systems for Curcumin as a Natural Source of Beneficial Health Effects.

This review discusses the impact of curcumin-an aromatic phytoextract from the turmeric (Curcuma longa) rhizome-as an effective therapeutic agent. Despite all of the beneficial health properties ensured by curcumin application, its pharmacological efficacy is compromised in vivo due to poor aqueous solubility, high metabolism, and rapid excretion that may result in poor systemic bioavailability. To overcome these problems, novel nanosystems have been proposed to enhance its bioavailability and bioactivity by reducing the particle size, the modification of surfaces, and the encapsulation efficiency of curcumin with different nanocarriers. The solutions based on nanotechnology can improve the perspective for medical patients with serious illnesses. In this review, we discuss commonly used curcumin-loaded bio-based nanoparticles that should be implemented for overcoming the innate constraints of this natural ingredient. Furthermore, the associated challenges regarding the potential applications in combination therapies are discussed as well.

Bilayer Mucoadhesive Buccal Film for Mucosal Ulcers Treatment: Development, Characterization, and Single Study Case.

The formation of mucosal ulcers is an end result of epithelial damage, and it occurs due to some specific causes, such as trauma, aphthous stomatitis, lichen planus and lichenoid reactions, cytotoxic effects of chemotherapy and radiation, and drug-induced hypersensitivity reactions and malignant settings. This study focused on films for target drug delivery with respect to the treatment of the diseases of the oral mucosa, specifically mucositis. The results of a single clinical study as a pre-experimental design was performed and followed up to the outcome until 30 days. The polymeric film was prepared in a mucoadhesive bilayer structure: the basal layer with lidocaine HCl had a faster release than the apical layer with benzydamine HCl and N-acetyl-cysteine. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and SEM characterized the physical-chemical and morphological properties. The cell viability and cytotoxicity were evaluated in cell line MCF7. The transport mechanism of the solvent (swelling) and the drugs in the basal or apical layer (drug release) was explained with mathematical models. To evaluate the effect of movement inside the mouth, the folding endurance was determined. The mucoadhesive bilayer film is biologically safe and stimulates cellular proliferation. A single study in vivo demonstrated the therapeutic effect of the mucoadhesive bilayer film in buccal mucositis.

Praziquantel-Solid Lipid Nanoparticles Produced by Supercritical Carbon Dioxide Extraction: Physicochemical Characterization, Release Profile, and Cytotoxicity.

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~-28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release of Curcumin.

AIMS AND BACKGROUND: The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801). MATERIALS AND METHODS: SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR. RESULTS: The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. CONCLUSION: Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties.

Production, stabilisation and characterisation of silver nanoparticles coated with bioactive polymers pluronic F68, PVP and PVA.

The increasing and alarming panorama of bacterial infections and associated morbidities that occur during medical and hospital procedures makes the development of technologies that aid in controlling such bacterial infections of utmost importance. Recent studies have shown that formulations with metal nanoparticles exhibit good antibacterial properties against a broad spectrum of microorganisms. Moreover, it was demonstrated that some biologically active polymeric materials, when applied in combination with chemical antimicrobial agents, enhance the therapeutic action of the latter. The research effort entertained herein aimed at the physico-chemical characterisation of silver nanoparticles obtained by chemical reduction, stabilised by bioactive polymers polyvinyl alcohol and polyvinylpyrrolidone, and further co-stabilised by pluronic F68. Scanning electron microscopy images of the nanoparticles produced, coated with different stabilisers, have shown that the chemical nature of the stabilisation effect promoted incorporation of pluronic in the nanoparticles and was closely related to an increase in the silver concentration in the nanoparticle samples obtained via energy-dispersive X-ray spectroscopy. The study described herein also shows that the nature of the stabiliser favours the interaction of pluronic F68 with samples containing silver nanoparticles.

Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence.

Cigarette smoking is a serious public health problem. According to data from the World Health Organization, it is estimated that currently more than 1.2 billion people worldwide do tobacco use and that smoking-related diseases are responsible for about 6 million deaths each. With attention to this, it is necessary to seek preventive and prognostic of trying to reduce these numbers and alert the public in general about the danger and the harm caused by its use. Thus, the objective of the research work undertaken was to evaluate and compare the chemical composition of collected saliva samples of smokers and nonsmokers by X-ray Fluorescence analyses. 32 individuals were selected, 16 of which used cigarette on a daily basis and the other 16 had never smoked. Saliva was collected with the help of a (sterile) disposable Pasteur pipette and samples sent to the Applied Nuclear Physics Laboratory at UNISO (LAFINAU), where analyzes were carried out. Individuals who agreed to participate in the study answered a questionnaire to define their profile of inclusion and signed an informed consent form (CEP Protocol no. 831.753 of 09/10/2014). The results clearly showed that there are differences in the concentrations of chemical elements in the saliva of smokers and non-smokers. The biggest discrepancies were found at concentrations of the chemical elements Sulfur, Phosphorus, Chlorine and Potassium, and smaller differences in the concentration of the elements Calcium, Manganese, Iron, Copper, Titanium, Vanadium and Nickel. In only one saliva sample, and in quite low amounts, arsenic was detected. The results indicate that smoking produces more significant changes in the saliva of women than in men, increasing the concentration of some elements in the saliva of female smokers, much more than in the male smokers. The cigarette usage time also appears to exert a greater influence on the composition of the saliva of women than in men, indicating that the damage caused by cigarette use may in fact be higher in women than in men.

Alternatives to overcoming bacterial resistances: State-of-the-art.

Worldwide, bacterial resistance to chemical antibiotics has reached such a high level that endangers public health. Presently, the adoption of alternative strategies that promote the elimination of resistant microbial strains from the environment is of utmost importance. This review discusses and analyses several (potential) alternative strategies to current chemical antibiotics. Bacteriophage (or phage) therapy, although not new, makes use of strictly lytic phage particles as an alternative, or a complement, in the antimicrobial treatment of bacterial infections. It is being rediscovered as a safe method, because these biological entities devoid of any metabolic machinery do not possess any affinity whatsoever to eukaryotic cells. Lysin therapy is also recognized as an innovative antimicrobial therapeutic option, since the topical administration of preparations containing purified recombinant lysins with amounts in the order of nanograms, in infections caused by Gram-positive bacteria, demonstrated a high therapeutic potential by causing immediate lysis of the target bacterial cells. Additionally, this therapy exhibits the potential to act synergistically when combined with certain chemical antibiotics already available on the market. Another potential alternative antimicrobial therapy is based on the use of antimicrobial peptides (AMPs), amphiphilic polypeptides that cause disruption of the bacterial membrane and can be used in the treatment of bacterial, fungal and viral infections, in the prevention of biofilm formation, and as antitumoral agents. Interestingly, bacteriocins are a common strategy of bacterial defense against other bacterial agents, eliminating the potential opponents of the former and increasing the number of available nutrients in the environment for their own growth. They can be applied in the food industry as biopreservatives and as probiotics, and also in fighting multi-resistant bacterial strains. The use of antibacterial antibodies promises to be extremely safe and effective. Additionally, vaccination emerges as one of the most promising preventive strategies. All these will be tackled in detail in this review paper.

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization.

The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 23×31 factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2 ± 2.6) nm and average Zeta potential of (-36.5 ± 0.9) mV, and exhibiting a polydispersity index of 0.206 ± 0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10-12 m2 s-1) as those published by other authors since, typically, diffusion coefficients for molecules range from 10-10 to 10-7 m2 s-1, but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10-12 m2 s-1.

Nanostructured Lipid Carriers as a Strategy to Improve the In Vitro Schistosomiasis Activity of Praziquantel.

Praziquantel (PZQ) is a pyrazinoisoquinoline anthelmintic that was discovered in 1972 by Bayer Germany. Currently, due to its efficacy, PZQ is the drug of choice against all species of Schistosoma. Although widely used, PZQ exhibits low and erratic bioavailability because of its poor water solubility. Nanostructured lipid carriers (NLC), second-generation solid lipid nanoparticles, were developed in the 1990s to improve the bioavailability of poorly water soluble drugs. The aim of this study was to investigate nanostructured lipid carriers as a strategy to improve the efficacy of PZQ in S. mansoni treatment. We prepared NLC2 and NLC4 by adding seventy percent glycerol monostearate (GMS) as the solid lipid, 30% oleic acid (OA) as the liquid lipid and two surfactant systems containing either soybean phosphatidylcholine/poloxamer (PC/P-407) or phosphatidylcholine/Tween 60 (PC/T60), respectively. The carriers were characterized by nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis and Fourier transform-infrared spectroscopy. The safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. The results showed that the encapsulation of PZQ in NLC2 or NLC4 improved the safety profile of the drug. Treatment efficacy was evaluated on the S. mansoni BH strain. PZQ-NLC2 and PZQ-NLC4 demonstrated an improved efficacy in comparison with free PZQ. The results showed that the intestinal transport of free PZQ and PZQ-NLC2 was similar. However, we observed that the concentration of PZQ absorbed was smaller when PZQ was loaded in NLC4. The difference between the amounts of absorbed PZQ could indicate that the presence of T60 in the nanoparticles (NLC4) increased the rigid lipid matrix, prolonging release of the drug. Both systems showed considerable in vitro activity against S. mansoni, suggesting that these systems may be a promising platform for the administration of PZQ for treating schistosomiasis.

Essential oils as active ingredients of lipid nanocarriers for chemotherapeutic use.

Essential oils have increased interest as promising ingredients for novel pharmaceutical dosage forms. These oils are reported to provide synergistic effects of their active ingredients, in parallel with their biodegradable properties. In addition, essential oils may also have therapeutic effects in diabetes, inflammation, cancer and to treat microbial infections. However, there are some physicochemical properties that may limit their use as active compounds in several formulations, such as high volatility, low-appealing organoleptic properties, low bioavailability and physicochemical instability, as result of exposure to light, oxygen and high temperatures. To overcome these limitations, lipid colloidal carriers (e.g. liposomes, solid lipid nanoparticles (SLN), self nanoemulsified drug delivery systems (SNEDDS)) have been pointed out as suitable carriers to improve bioavailability, low solubility, taste, flavor and long-term storage of sensitive compounds. This paper reviews the potential beneficial effects of formulating essential oils in pharmaceutical applications using colloidal carriers as delivery systems.

Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and cell viability studies (Caco-2 & HEPG-2 cell lines).

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens.