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.

A randomized controlled trial to test the effectiveness of two technology-enhanced diabetes prevention programs in primary care: The DiaBEAT-it study.

Objective: To evaluate the effectiveness of two technology-enhanced interventions for diabetes prevention among adults at risk for developing diabetes in a primary care setting. Methods: The DiaBEAT-it study employed a hybrid 2-group preference (Choice) and 3-group randomized controlled (RCT) design. This paper presents weight related primary outcomes of the RCT arm. Patients from Southwest Virginia were identified through the Carilion Clinic electronic health records. Eligible participants (18 and older, BMI ≥ 25, no Type 2 Diabetes) were randomized to either Choice (n = 264) or RCT (n = 334). RCT individuals were further randomized to one of three groups: (1) a 2-h small group class to help patients develop a personal action plan to prevent diabetes (SC, n = 117); (2) a 2-h small group class plus automated telephone calls using an interactive voice response system (IVR) to help participants initiate weight loss through a healthful diet and regular physical activity (Class/IVR, n = 110); or (3) a DVD with same content as the class plus the same IVR calls over a period of 12 months (DVD/IVR, n = 107). Results: Of the 334 participants that were randomized, 232 (69%) had study measured weights at 6 months, 221 (66%) at 12 months, and 208 (62%) at 18 months. Class/IVR participants were less likely to complete weight measures than SC or DVD/IVR. Intention to treat analyses, controlling for gender, race, age and baseline BMI, showed that DVD/IVR and Class/IVR led to reductions in BMI at 6 (DVD/IVR -0.94, p < 0.001; Class/IVR -0.70, p < 0.01), 12 (DVD/IVR -0.88, p < 0.001; Class/IVR-0.82, p < 0.001) and 18 (DVD/IVR -0.78, p < 0.001; Class/IVR -0.58, p < 0.01) months. All three groups showed a significant number of participants losing at least 5% of their body weight at 12 months (DVD/IVR 26.87%; Class/IVR 21.62%; SC 16.85%). When comparing groups, DVD/IVR were significantly more likely to decrease BMI at 6 months (p < 0.05) and maintain the reduction at 18 months (p < 0.05) when compared to SC. There were no differences between the other groups. Conclusions: The DiaBEAT-it interventions show promise in responding to the need for scalable, effective methods to manage obesity and prevent diabetes in primary care settings that do not over burden primary care clinics and providers. Registration: https://clinicaltrials.gov/ct2/show/NCT02162901, identifier: NCT02162901.

Nanotechnology-Based Dressings for Wound Management.

Wound healing is known to be a complicated and intricate process and commonly classified as chronic or acute. Patients with chronic wounds are of public health concern, and require more attention onto skin lesions, including atopic dermatitis. Despite being a natural process, healing can be impaired by existing chronic de diseases such as diabetes, for example. Recently, wound dressings based in nanotechnology systems have emerged as a viable option to improve the healing process. Current advances in nanotechnology-based systems to release growth factors and bioactive agents represent a great opportunity to develop new therapies for wound treatments. It is essential that healthcare professionals understand the key processes involved in the healing cascade, to maximize care with these patients and minimize the undesirable outcomes of non-healing wounds. Therefore, this review aims to summarize the healing process phases and provide a general overview of dressings based in nanotechnology using biomaterials for the release of active agents in wound site.

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.

Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications.

As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. The design of an efficient ocular drug delivery system still remains a challenge. Although nanotechnology may offer the ability to detect and treat eye diseases, successful treatment approaches are still in demand. The growing interest in nanopharmaceuticals offers the opportunity to improve ophthalmic treatments. Besides their size, which needs to be critically monitored, nanopharmaceuticals for ophthalmic applications have to be produced under sterilized conditions. In this work, we have revised the different sterilization and depyrogenation methods for ophthalmic nanopharmaceuticals with their merits and drawbacks. The paper also describes clinical sterilization of drugs and the outcomes of inappropriate practices, while recent applications of nanopharmaceuticals for ocular drug delivery are also addressed.

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.

Alternative Cutaneous Substitutes Based on Poly(l-co-d,l-lactic acid-co-trimethylene carbonate) with Schinus terebinthifolius Raddi Extract Designed for Skin Healing.

The search for new therapies and drugs that act as topical agents to relieve pain and control the inflammatory processes in burns always attracted interest in clinical trials. As an alternative to synthetic drugs, natural extracts are useful in the development of new strategies and formulations for improving the quality of life. The aim of this study was to develop a wound dressing using poly(l-co-d,l-lactic acid-co-trimethylene carbonate) (PLDLA-TMC) containing Schinus terebinthifolius Raddi (S.T.R.). S.T.R. is a native Brazilian plant known for its strong anti-inflammatory responses. The membrane of PLDLA-TMC + S. terebinthifolius Raddi was prepared at different concentrations of S.T.R. (5, 10, 15, and 50%). The Fourier transform infrared results showed no change in the PLDLA-TMC spectrum after S.T.R. addition, whereas the swelling test showed changes only in PLDLA-TMC + S.T.R. at 50%. The wettability measurements showed a mass loss due to the decrease in the contact angle in all samples after the S.T.R. addition in the polymer, whereas the S.T.R. release test showed a linear delivery pattern. The scanning electron microscopy analysis showed that S.T.R. was homogeneously distributed at only 5 and 10%. Tensile tests demonstrated an increase in Young's modulus and a reduction in the elongation till rupture of PLDLA-TMC after the addition of S.T.R. The biocompatibility in vitro evaluation with rat fibroblast cells seeded in the membranes of PLDLA-TMC + S.T.R. showed that although S.T.R. interfered in cell morphology, all concentrations tested showed that cells were able to adhere and proliferate during 7 days. Thus, S.T.R. at 50% was chosen to be tested for in vivo trials. The histological and immunohistochemistry results revealed an accelerated skin healing at 7 days after controlled secondary burns were introduced in the dorsal skin, with a striking total recovery of the epidermis and high rates of molecular activation of cell proliferation. Due to the known biocompatibility properties of PLDLA-TMC and its stable release of S.T.R., we strongly recommend S.T.R.-containing PLDLA-TMC as a curative device to favor skin healing.

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.

Spotlight on Biomimetic Systems Based on Lyotropic Liquid Crystal.

The behavior of lyotropic biomimetic systems in drug delivery was reviewed. These behaviors are influenced by drug properties, the initial water content, type of lyotropic liquid crystals (LLC), swell ability, drug loading rate, the presence of ions with higher or less kosmotropic or chaotropic force, and the electrostatic interaction between the drug and the lipid bilayers. The in vivo interaction between LCC-drugs, and the impact on the bioavailability of drugs, was reviewed. The LLC with a different architecture can be formed by the self-assembly of lipids in aqueous medium, and can be tuned by the structures and physical properties of the emulsion. These LLC lamellar phase, cubic phase, and hexagonal phase, possess fascinating viscoelastic properties, which make them useful as a dispersion technology, and a highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix for drug delivery. In addition, the biodegradable and biocompatible nature of lipids demonstrates a minimum toxicity and thus, they are used for various routes of administration. This review is not intended to provide a comprehensive overview, but focuses on the advantages over non modified conventional materials and LLC biomimetic properties.

Scaffolds and tissue regeneration: An overview of the functional properties of selected organic tissues.

Tissue engineering plays a significant role both in the re-establishment of functions and regeneration of organic tissues. Success in manufacturing projects for biological scaffolds, for the purpose of tissue regeneration, is conditioned by the selection of parameters such as the biomaterial, the device architecture, and the specificities of the cells making up the organic tissue to create, in vivo, a microenvironment that preserves and further enhances the proliferation of a specific cell phenotype. To support this approach, we have screened scientific publications that show biomedical applications of scaffolds, biomechanical, morphological, biochemical, and hemodynamic characteristics of the target organic tissues, and the possible interactions between different cell matrices and biological scaffolds. This review article provides an overview on the biomedical application of scaffolds and on the characteristics of the (bio)materials commonly used for manufacturing these biological devices used in tissue engineering, taking into consideration the cellular specificity of the target tissue. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1483-1494, 2016.