A Hyphenated Approach Combining Pressure-Decay and in Situ FT-NIR Spectroscopy to Monitor Penetrant Sorption and Concurrent Swelling in Polymers

A new hyphenated technique based on simultaneous in situ FT-NIR spectroscopy and pressure-decay measurements has been implemented to study sorption of low-molecular-weight compounds in polymeric membranes and the induced swelling of the matrix. The FT-NIR measurements are performed in the transmission mode and, besides sorption equilibrium and kinetics, allow also the straightforward measurement of polymer swelling. The pressure decay method is used to provide quantitative information on the concentration of penetrant sorbed in the polymer. This measurement, once combined with the photometric data, allows an accurate estimation of the molar absorptivity of the analytical peaks as well. To validate the new experimental approach, sorption of CO2 in polydimethylsiloxane at 35 °C and at pressures up to 9 bar has been investigated and the results are compared with available literature data

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.[Figure not available: see fulltext.

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

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

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. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

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. This journal i

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. © 2019 American Chemical Society

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. [Image: see text