Bioactive chitosan/poly(ethyleneoxide)/CuFe2O4 nanofibers for potential wound healing.

Wound healing is a complex process that often requires intervention to accelerate tissue regeneration and prevent complications. The goal of this research was to assess the potential of bioactive chitosan@poly (ethylene oxide)@CuFe2O4 (CS@PEO@CF) nanofibers for wound healing applications by evaluating their morphology, mechanical properties, and magnetic behavior. Additionally, in vitro and in vivo studies were conducted to investigate their effectiveness in promoting wound healing treatment. The nanoparticles exhibited remarkable antibacterial and antioxidant properties. In the nanofibrous mats, the optimal concentration of CuFe2O4 was determined to be 0.1% Wt/V. Importantly, this concentration did not adversely affect the viability of fibroblast cells, which also identified the ideal concentration. The scaffold's hemocompatibility revealed nonhemolytic properties. Additionally, a wound-healing experiment demonstrated significant migration and growth of fibroblast cells at the edge of the wound. These nanofibrous mats are applied to treat rats with full-thickness excisional wounds. Histopathological analysis of these wounds showed enhanced wound healing ability, as well as regeneration of sebaceous glands and hair follicles within the skin. Overall, the developed wound dressing comprises CuFe2O4 nanoparticles incorporated into CS/PEO nanofibrous mats demonstrating its potential for successful application in wound treatment.

PLGA microparticle formulations for tunable delivery of a nano-engineered filamentous bacteriophage-based vaccine: in vitro and in silico-supported approach.

Bacteriophages have attracted great attention in the bioengineering field in diverse research areas from tissue engineering to therapeutic and clinical applications. Recombinant filamentous bacteriophage, carrying multiple copies of foreign peptides on protein capsid has been successfully used in the vaccine delivery setting, even if their plasma instability and degradation have limited their use on the pharmaceutical market. Encapsulation techniques in polymeric materials can be applied to preserve bacteriophage activity, extend its half-life, and finely regulate their release in the target environment. The main goal of this study was to provide tunable formulations of the bacteriophage encapsulated in polymeric microparticles (MPs). We used poly (lactic-co-glycolic-acid) as a biocompatible and biodegradable polymer with ammonium bicarbonate as a porogen to encapsulate bacteriophage expressing OVA (257-264) antigenic peptide. We demonstrate that nano-engineered fdOVA bacteriophages encapsulated in MPs preserve their structure and are immunologically active, inducing a strong immune response towards the delivered peptide. Moreover, MP encapsulation prolongs bacteriophage stability over time also at room temperature. Additionally, in this study, we show the ability of in silico-supported approach to predict and tune the release of bacteriophages. These results lay the framework for a versatile bacteriophage-based vaccine delivery system that could successfully generate robust immune responses in a sustained manner, to be used as a platform against cancer and new emerging diseases. Graphical abstract: Synopsis: administration of recombinant bacteriophage-loaded PLGA microparticles for antigen delivery. PLGA microparticles release the bacteriophages, inducing activation of dendritic cells and enhancing antigen presentation and specific T cell response. Bacteriophage-encapsulated microneedles potentially can be administered into human body and generate robust immune responses.

Long-Term Vaccine Delivery and Immunological Responses Using Biodegradable Polymer-Based Carriers.

Biodegradable polymers are largely employed in the biomedical field, ranging from tissue regeneration to drug/vaccine delivery. The biodegradable polymers are highly biocompatible and possess negligible toxicity. In addition, biomaterial-based vaccines possess adjuvant properties, thereby enhancing immune responses. This Review introduces the use of different biodegradable polymers and their degradation mechanism. Different kinds of vaccines, as well as the interaction between the carriers with the immune system, then are highlighted. Natural and synthetic biodegradable micro-/nanoplatforms, hydrogels, and scaffolds for local or targeted and controlled vaccine release are subsequently discussed.

Recent Fabrication Methods to Produce Polymer-Based Drug Delivery Matrices (Experimental and In Silico Approaches).

The study of novel drug delivery systems represents one of the frontiers of the biomedical research area. Multi-disciplinary scientific approaches combining traditional or engineered technologies are used to provide major advances in improving drug bioavailability, rate of release, cell/tissue specificity and therapeutic index. Biodegradable and bio-absorbable polymers are usually the building blocks of these systems, and their copolymers are employed to create delivery components. For example, poly (lactic acid) or poly (glycolic acid) are often used as bricks for the production drug-based delivery systems as polymeric microparticles (MPs) or micron-scale needles. To avoid time-consuming empirical approaches for the optimization of these formulations, in silico-supported models have been developed. These methods can predict and tune the release of different drugs starting from designed combinations. Starting from these considerations, this review has the aim of investigating recent approaches to the production of polymeric carriers and the combination of in silico and experimental methods as promising platforms in the biomedical field.

Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion.

Transdermal microneedle (MN) patches are a promising tool used to transport a wide variety of active compounds into the skin. To serve as a substitute for common hypodermic needles, MNs must pierce the human stratum corneum (~ 10 to 20 µm), without rupturing or bending during penetration. This ensures that the cargo is released at the predetermined place and time. Therefore, the ability of MN patches to sufficiently pierce the skin is a crucial requirement. In the current review, the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared. This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice. Factors that affect insertion (e.g., geometry, material composition and cross-linking of MNs), along with recent advancements in developed strategies (e.g., insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography) to improve the skin penetration are highlighted to provide a backdrop for future research.

Stimuli-responsive transdermal microneedle patches.

Microneedle (MN) patches consisting of miniature needles have emerged as a promising tool to perforate the stratum corneum and translocate biomolecules into the dermis in a minimally invasive manner. Stimuli-responsive MN patches represent emerging drug delivery systems that release cargos on-demand as a response to internal or external triggers. In this review, a variety of stimuli-responsive MN patches for controlled drug release are introduced, covering the mechanisms of action toward different indications. Future opportunities and challenges with respect to clinical translation are also discussed.

Design of biodegradable bi-compartmental microneedles for the stabilization and the controlled release of the labile molecule collagenase for skin healthcare.

Proteins are widely explored as therapeutic agents, but some issues remain alive in their delivery versus target tissues and organs. Especially in the case of water-labile proteins, they undergo rapid failure if not properly stored or once they have encountered the biological environment. In this framework, delivery systems can be very useful to protect such proteins both during storage and during their administration. In particular, polymer microneedles (MNs) represent an interesting tool for the in vivo administration of proteins, avoiding the aggressive gastrointestinal or blood environment. Here, polymer microneedles for the encapsulation and delivery of the labile protein collagenase are presented. Polyvinylpyrrolidone-hyaluronic acid (PVP-HA) microneedles with embedded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) were designed in order to achieve a sustained but relatively fast release of the enzyme to avoid its long exposure to water upon administration. PLGA-MPs with tunable porosity were produced by means of a modified double emulsion protocol and their morphological and kinetic properties were characterized by different analytic techniques. Diffusion studies and in vivo experiments were used to assess the release and indentation ability of the proposed MP-based microneedles. The obtained results recommend our bi-compartmental system as a promising biomedical technique paving the way for its efficient use in treating human diseases with labile therapeutic agents.

Advances in Antimicrobial Microneedle Patches for Combating Infections.

Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.

Recombinant Filamentous Bacteriophages Encapsulated in Biodegradable Polymeric Microparticles for Stimulation of Innate and Adaptive Immune Responses.

Escherichia coli filamentous bacteriophages (M13, f1, or fd) have attracted tremendous attention from vaccinologists as a promising immunogenic carrier and vaccine delivery vehicle with vast possible applications in the development of vaccines. The use of fd bacteriophage as an antigen delivery system is based on a modification of bacteriophage display technology. In particular, it is designed to express multiple copies of exogenous peptides (or polypeptides) covalently linked to viral capsid proteins. This study for the first time proposes the use of microparticles (MPs) made of poly (lactic-co-glycolic acid)(PLGA) to encapsulate fd bacteriophage. Bacteriophage-PLGA MPs were synthesized by a water in oil in water (w1/o/w2) emulsion technique, and their morphological properties were analyzed by confocal and scanning electron microscopy (SEM). Moreover, phage integrity, encapsulation efficiency, and release were investigated. Using recombinant bacteriophages expressing the ovalbumin (OVA) antigenic determinant, we demonstrated the immunogenicity of the encapsulated bacteriophage after being released by MPs. Our results reveal that encapsulated bacteriophages are stable and retain their immunogenic properties. Bacteriophage-encapsulated PLGA microparticles may thus represent an important tool for the development of different bacteriophage-based vaccine platforms.

Progress in Microneedle-Mediated Protein Delivery.

The growing demand for patient-compliance therapies in recent years has led to the development of transdermal drug delivery, which possesses several advantages compared with conventional methods. Delivering protein through the skin by transdermal patches is extremely difficult due to the presence of the stratum corneum which restricts the application to lipophilic drugs with relatively low molecular weight. To overcome these limitations, microneedle (MN) patches, consisting of micro/miniature-sized needles, are a promising tool to perforate the stratum corneum and to release drugs and proteins into the dermis following a non-invasive route. This review investigates the fabrication methods, protein delivery, and translational considerations for the industrial scaling-up of polymeric MNs for dermal protein delivery.

Metal-Based Nanostructures/PLGA Nanocomposites: Antimicrobial Activity, Cytotoxicity, and Their Biomedical Applications.

Among the different synthetic polymers developed for biomedical applications, poly(lactic-co-glycolic acid) (PLGA) has attracted considerable attention because of its excellent biocompatibility and biodegradability. Nanocomposites based on PLGA and metal-based nanostructures (MNSs) have been employed extensively as an efficient strategy to improve the structural and functional properties of PLGA polymer. The MNSs have been used to impart new properties to PLGA, such as antimicrobial properties and labeling. In the present review, the different strategies available for the fabrication of MNS/PLGA nanocomposites and their applications in the biomedical field will be discussed, beginning with a description of the preparation routes, antimicrobial activity, and cytotoxicity concerns of MNS/PLGA nanocomposites. The biomedical applications of these nanocomposites, such as carriers and scaffolds in tissue regeneration and other therapies are subsequently reviewed. In addition, the potential advantages of using MNS/PLGA nanocomposites in treatment illnesses are analyzed based on in vitro and in vivo studies, to support the potential of these nanocomposites in future research in the biomedical field.

Non-invasive Production of Multi-Compartmental Biodegradable Polymer Microneedles for Controlled Intradermal Drug Release of Labile Molecules.

Transdermal drug delivery represents an appealing alternative to conventional drug administration systems. In fact, due to their high patient compliance, the development of dissolvable and biodegradable polymer microneedles has recently attracted great attention. Although stamp-based procedures guarantee high tip resolution and reproducibility, they have long processing times, low levels of system engineering, are a source of possible contaminants, and thermo-sensitive drugs cannot be used in conjunction with them. In this work, a novel stamp-based microneedle fabrication method is proposed. It provides a rapid room-temperature production of multi-compartmental biodegradable polymeric microneedles for controlled intradermal drug release. Solvent casting was carried out for only a few minutes and produced a short dissolvable tip made of polyvinylpyrrolidone (PVP). The rest of the stamp was then filled with degradable poly(lactide-co-glycolide) (PLGA) microparticles (µPs) quickly compacted with a vapor-assisted plasticization. The outcome was an array of microneedles with tunable release. The ability of the resulting microneedles to indent was assessed using pig cadaver skin. Controlled intradermal delivery was demonstrated by loading both the tip and the body of the microneedles with model therapeutics; POXA1b laccase from Pleurotus ostreatus is a commercial enzyme used for the whitening of skin spots. The action and indentation of the enzyme-loaded microneedle action were assessed in an in vitro skin model and this highlighted their ability to control the kinetic release of the encapsulated compound.

Antibacterial quaternary ammonium compounds in dental materials: A systematic review.

OBJECTIVE: Quaternary ammonium compounds (QACs) represent one of the most effective classes of disinfectant agents in dental materials and resin nanocomposites. This reviews aims to give a wide overview on the research in the field of antibacterial QACs in dental materials and nanocomposites. METHOD: An introduction to dental materials components as well as the microorganisms and methods of evaluation for the antimicrobial assays are presented. Then, the properties and synthesis route of QACs, as monomer and filler, are shown. Finally, antimicrobial monomers and fillers, specifically those contain quaternary ammonium salts (QASs), in dental materials are reviewed. RESULTS: QACs have been used as monomer and micro/nanofiller in restorative dentistry. They possess one or more methacrylate functional groups to participate in polymerization reactions. QACs with multiple methacrylate groups can also be used as crosslinking agents. Furthermore, QACs with chain length from ∼12 to 16 have higher antimicrobial activity in cured dental resins. In general, increasing the chain length leads to a threshold value (critical point) and then it causes decrease in the antimicrobial activity. SIGNIFICANCE: The current state of the art of dental materials and resin nanocomposites includes a wide variety of antimicrobial materials. Among them, QACs presents low cytotoxicity and excellent long-term antimicrobial activity without leaching out over time.