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The first potent leukotriene B4 (LTB4) receptor type 2 (BLT2) agonists, endogenous 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), and synthetic CAY10583 (CAY) have been recently described to accelerate wound healing by enhanced keratinocyte migration and indirect stimulation of fibroblast activity in diabetic rats. CAY represents a very valuable starting point for the development of novel wound-healing promoters. In this work, the first structure-activity relationship study for CAY scaffold-based BLT2 agonists is presented. The newly prepared derivatives showed promising in vitro wound-healing activity.

Therapeutic management of skin wounds is still faced with major challenges associated with chronicity and bacterial infection. Consequently, there is a high clinical need for effective therapeutic approaches addressing these aspects. In this context, electrospun fibers emerged as beneficial carrier systems for local and controlled delivery of wound healing agents, additionally providing a protective barrier against bacterial invasion. However, depending on the material, such fibers were also shown to provide a potential substrate for bacterial colonization and growth. Thus, profound understanding of fiber characteristics and the respective interactions of fibers with biological systems, cells as well as bacteria, is of major importance. To address these issues, we designed drug-loaded hybrid fibers consisting of polycaprolactone (PCL) and chitosan. Pure PCL fibers provided suitable drug release kinetics for wound healing, but were colonized by Pseudomonas bacteria which were used as model pathogens. The addition of chitosan to the fiber matrix reduced the number of adherent bacteria by tenfold compared to pure PCL fibers and did not show any adverse effects to human skin cells. Further, chitosan incorporation significantly improved fiber hydrophilicity, identified as one of the key regulators of optimized cell-fiber interactions. We successfully encapsulated dexpanthenol as an established wound healing active into these hybrid fibers and solvent polarity was found to be a key factor for controlling drug release kinetics from the fibers. For the final formulation, controlled drug release over seven days with a burst release of 11.54% within 3 h could be achieved and the wound healing effect of the fiber mats could successfully be demonstrated in a cell-based wound healing assay as a proof-of-concept. Such multifunctional fibers simultaneously deliver actives and prevent bacterial growth, and consequently show a high potential for future wound therapy.

Therapeutic application of pharmacologically active proteins requires advanced drug delivery systems for stabilizing their activity and preventing denaturation during storage and patient treatment. Depending on their clinical target, controlled drug release is often required to achieve the intended therapeutic effect. In this context, electrospun nanofibers gained considerable attention. However, even though immediate drug release from such fibers can easily be realized, fiber mat fabrication providing long-term controlled protein release still bares challenges. In this study, lysozyme was encapsulated in poly(vinyl alcohol) fibers followed by post-modification with MeOH, glutaraldehyde vapor, or UV light. Subsequently, a systematic investigation of the effect of these post-modification treatments on the physicochemical properties of the fibers and the stability and release kinetics of lysozyme was performed. MeOH treatment did not affect lysozyme release kinetics compared to untreated fibers, whereas glutaraldehyde vapor and UV light treatment prolonged the drug release. Infrared spectroscopy revealed cross-linking of the polymer by glutaraldehyde vapor, which reduced the lysozyme release from the fibers. Further, protein activity was significantly reduced for fibers treated with glutaraldehyde vapor and UV light. In addition, reduced viability was identified for cells in contact with glutaraldehyde vapor-treated fibers and, to a lesser extent, for UV light-treated fibers, whereas MeOH-treated fibers did not affect cell viability. These results elucidated the effects of fiber post-modification on the release kinetics, activity, and biocompatibility of protein drugs and can serve as guidance for rational development of nanomedicines for safe and effective therapeutic delivery of natural proteins.

Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein-based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein-based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic applications. This review provides a comprehensive overview of the current state of protein-based carrier systems using electrospun fibers, with special emphasis on discussing their potential and key challenges in developing such therapeutic strategies, along with a prospective view of anticipated future directions.