Recent Developments in 3D-(Bio)printed Hydrogels as Wound Dressings.

Wound healing is a physiological process occurring after the onset of a skin lesion aiming to reconstruct the dermal barrier between the external environment and the body. Depending on the nature and duration of the healing process, wounds are classified as acute (e.g.

Development of Composite Nanostructured Electrodes for Water Desalination via Membrane Capacitive Deionization.

Novel two-layer nanostructured electrodes are successfully prepared for their application in membrane capacitive deionization (MCDI) processes. Nanostructured carbonaceous materials such as graphene oxide (GO) and carbon nanotubes (CNTs), as well as activated carbon (AC) are dispersed in a solution of poly(vinyl alcohol) (PVA), mixed with polyacrylic acid (PAA) or polydimethyldiallylammonium chloride (PDMDAAC), and subsequently cast on the top surface of an AC-based modified graphite electrode to form a thin composite layer that is cross-linked with glutaraldehyde (GA). Cyclic voltammetry (CV) is performed to investigate the electrochemical properties of the composite electrodes and desalination experiments are conducted in batch mode using a MCDI unit cell to investigate the effects of i) the nanostructured carbonaceous material, ii) its concentration in the polymer blend, and iii) the molecular weight of the polymers on the desalination efficiency of the system.

Development of a novel squalene/α-tocopherol-based self-emulsified nanoemulsion incorporating Leishmania peptides for induction of antigen-specific immune responses.

Vaccination has emerged as the most effective strategy to confront infectious diseases, among which is leishmaniasis, that threat public health. Despite laborious efforts there is still no vaccine for humans to confront leishmaniasis. Multi-epitope protein/peptide vaccines present a number of advantages, however their use along with appropriate adjuvants that may also act as antigen carriers is considered essential to overcome subunit vaccines' low immunogenicity.

A liposomal vaccine promotes strong adaptive immune responses via dendritic cell activation in draining lymph nodes.

Subunit proteins provide a safe source of antigens for vaccine development especially for intracellular infections which require the induction of strong cellular immune responses. However, those antigens are often limited by their low immunogenicity. In order to achieve effective immune responses, they should be encapsulated into a stable antigen delivery system combined with an appropriate adjuvant.

Model-based optimization of drug release rate from a size distributed population of biodegradable polymer carriers.

In the present study, a comprehensive polymer degradation-drug diffusion model is developed to describe the polymer degradation kinetics and quantify the release rate of an active pharmaceutical ingredient (API) from a size-distributed population of drug-loaded poly(lactic-co-glycolic) acid (PLGA) carriers in terms of material and morphological properties of the drug carriers. To take into account the spatial-temporal variation of the drug and water diffusion coefficients, three new correlations are developed in terms of spatial-temporal variation of the molecular weight of the degrading polymer chains. The first one relates the diffusion coefficients with the time-spatial variation of the molecular weight of PLGA and initial drug loading and, the second one with the initial particle size, and the third one with evolution of the particle porosity due to polymer degradation.

Immunoinformatics Approach to Design a Multi-Epitope Nanovaccine against Parasite: Elicitation of Cellular Immune Responses.

Leishmaniasis is a vector-borne disease caused by an intracellular parasite of the genus with different clinical manifestations that affect millions of people worldwide, while the visceral form may be fatal if left untreated. Since the available chemotherapeutic agents are not satisfactory, vaccination emerges as the most promising strategy for confronting leishmaniasis. In the present study, a reverse vaccinology approach was adopted to design a pipeline starting from proteome analysis of three different species and ending with the selection of a pool of MHCI- and MHCII-binding epitopes.

Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications.

Articular cartilage lesions resulting from injurious impact, recurring loading, joint malalignment, etc., are very common and encompass the risk of evolving to serious cartilage diseases such as osteoarthritis. To date, cartilage injuries are typically treated via operative procedures such as autologous chondrocyte implantation (ACI), matrix-associated autologous chondrocyte implantation (MACI) and microfracture, which are characterized by low patient compliance.

Prediction of Viscoelastic Properties of Enzymatically Crosslinkable Tyramine-Modified Hyaluronic Acid Solutions Using a Dynamic Monte Carlo Kinetic Approach.

The present study deals with the mathematical modeling of crosslinking kinetics of polymer-phenol conjugates mediated by the Horseradish Peroxidase (HRP)-hydrogen peroxide (HO) initiation system. More specifically, a dynamic Monte Carlo (MC) kinetic model is developed to quantify the effects of crosslinking conditions (i.e.

Biomimetic Cell-Laden MeHA Hydrogels for the Regeneration of Cartilage Tissue.

Methacrylated hyaluronic acid (MeHA) and chondroitin sulfate (CS)-biofunctionalized MeHA (CS-MeHA), were crosslinked in the presence of a matrix metalloproteinase 7 (MMP7)-sensitive peptide. The synthesized hydrogels were embedded with either human mesenchymal stem cells (hMSCs) or chondrocytes, at low concentrations, and subsequently cultured in a stem cell medium (SCM) or chondrogenic induction medium (CiM). The pivotal role of the synthesized hydrogels in promoting the expression of cartilage-related genes and the formation of neocartilage tissue despite the low concentration of encapsulated cells was assessed.

Recent Advances in Antigen-Specific Immunotherapies for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy.

Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice.

Visceral leishmaniasis (VL) caused by and . is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development.

Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics.

Central nervous system (CNS) disorders (e.g., multiple sclerosis, Alzheimer's disease, etc.

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis.

Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with parasites in BALB/c mice.

A Poly(Lactic--Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8 T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.

Visceral leishmaniasis, caused by (.) and protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4 T and CD8 T cells.

Model-based intensification of a fed-batch microbial process for the maximization of polyhydroxybutyrate (PHB) production rate.

An integrated metabolic-polymerization-macroscopic model, describing the microbial production of polyhydroxybutyrate (PHB) in Azohydromonas lata bacteria, was developed and validated using a comprehensive series of experimental measurements. The model accounted for biomass growth, biopolymer accumulation, carbon and nitrogen sources utilization, oxygen mass transfer and uptake rates and average molecular weights of the accumulated PHB, produced under batch and fed-batch cultivation conditions. Model predictions were in excellent agreement with experimental measurements.

Recent developments in nanocarrier-aided mucosal vaccination.

To date, most of the licensed vaccines for mucosal delivery are based on live-attenuated viruses which carry the risk of regaining their pathogenicity. Therefore, the development of efficient nonviral vectors allowing the induction of potent humoral and cell-mediated immunity is regarded as an imperative scientific challenge as well as a commercial breakthrough for the pharma industries. For a successful translation to the clinic, such nanocarriers should protect the antigens from mucosal enzymes, facilitate antigen uptake by microfold cells and allow the copresentation of robust, safe for human use, mucosal adjuvants to antigen-presenting cells.

Identification of BALB/c Immune Markers Correlated with a Partial Protection to Leishmania infantum after Vaccination with a Rationally Designed Multi-epitope Cysteine Protease A Peptide-Based Nanovaccine.

Background: Through their increased potential to be engaged and processed by dendritic cells (DCs), nanovaccines consisting of Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with both antigenic moieties and adjuvants are attractive candidates for triggering specific defense mechanisms against intracellular pathogens. The aim of the present study was to evaluate the immunogenicity and prophylactic potential of a rationally designed multi-epitope peptide of Leishmania Cysteine Protease A (CPA160-189) co-encapsulated with Monophosphoryl lipid A (MPLA) in PLGA NPs against L. infantum in BALB/c mice and identify immune markers correlated with protective responses.

Optimization of a DPI Inhaler: A Computational Approach.

Alternate geometries of a commercial dry powder inhaler (DPI, i.e., Turbuhaler; AstraZeneca, London, UK) are proposed based on the simulation results obtained from a fluid and particle dynamic computational model, previously developed by Milenkovic et al.

Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics.

The oral administration of protein therapeutics is hindered by the multitude of barriers confronted by these molecules along the gastrointestinal tract (i.e., acidic environment, proteolytic degradation, mucosal barrier, etc.

Lipid-based nanocarriers for the oral administration of biopharmaceutics.

Biopharmaceutics have been recognized as the drugs of choice for the treatment of several diseases, mainly due to their high selectivity and potent action. Nonetheless, their oral administration is a rather challenging problem, since their bioavailability is significantly hindered by various physiological barriers along the GI tract, including their acid-induced hydrolysis in the stomach, their enzymatic degradation throughout the GI tract and their poor mucosa permeability. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of biomolecules while diminishing toxicity-related issues.

PLGA nanoparticles modified with a TNFα mimicking peptide, soluble Leishmania antigens and MPLA induce T cell priming in vitro via dendritic cell functional differentiation.

Poly(lactide-co-glycolide) nanoparticles (PLGA NPs) represent a new approach for vaccine delivery due to their ability to be taken up by phagocytes and to activate immune responses. In the present study PLGA NPs were surface-modified with a TNFα mimicking peptide, and encapsulated soluble Leishmania antigens (sLiAg) and MPLA adjuvant. The synthesized PLGA NPs exhibited low cytotoxicity levels, while surface-modified NPs were more efficiently taken up by dendritic cells (DCs).

Effective incorporation of insulin in mucus permeating self-nanoemulsifying drug delivery systems.

The development of a novel, mucus permeating SNEDDS formulation for oral insulin delivery containing a hydrophobic ion pair of insulin/dimyristoyl phosphatidylglycerol (INS/DMPG) is presented. Three oil/surfactant/cosurfactant combinations and 27 weight ratios of oil, surfactant and cosurfactant for each combination were evaluated with the aid of ternary phase diagrams, for the incorporation of the protein/phospholipid complex. The developed formulation was characterized by an average droplet diameter of 30-45 nm.

On the synthesis of mucus permeating nanocarriers.

The synthesis of nanocarriers with "slippery" surface (i.e., poly(lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) and polyelectrolyte complexes (PECs) of polyacrylic acid (PAA) with poly-L-lysine (PLL) and/or polyarginine (PArg)) and of nanocarriers (i.

Computational model of particle deposition in the nasal cavity under steady and dynamic flow.

A computational model for flow and particle deposition in a three-dimensional representation of the human nasal cavity is developed. Simulations of steady state and dynamic airflow during inhalation are performed at flow rates of 9-60 l/min. Depositions for particles of size 0.

Recent advances in nanocarrier-based mucosal delivery of biomolecules.

This review highlights the recent developments in the area of nanocarrier-based mucosal delivery of therapeutic biomolecules and antigens. Macromolecular drugs have the unique power to tackle challenging diseases but their structure, physicochemical properties, stability, pharmacodynamics, and pharmacokinetics place stringent demands on the way they are delivered into the body (e.g.