NEW FRONTIERS IN TRANSDERMAL DELIVERY AND WOUND HEALING: ADVANCING DRUG DELIVERY SYSTEMS VIA MICROFLUIDICS, 3D PRINTING, AND SOLUTION BLOW-SPINNING.

Skin-mediated drug delivery has gained significant popularity over the past decade, mainly due to the rising demand for patient-friendly alternatives to oral and injectable medications. However, conventional transdermal treatments face issues, such as limited permeability and lack of customization, that restrict their widespread use. These limitations have paved the way for reshaping the future of next-generation transdermal systems through innovative manufacturing methods. This thesis investigates the revolutionary impact of cutting-edge technologies, such as microfluidics, 3D printing, and solution blow spinning on the development of transdermal delivery and wound-healing systems, using research findings from my PhD program. Specifically, Part I reports the successful use of a microfluidic-assisted ionotropic gelation technique to produce peptide-loaded chitosan nanoparticles (Cs NPs) with improved skin penetration. Argireline, selected as the model peptide due to its hydrophilic nature and high molecular weight (factors that typically hinder transdermal delivery), was encapsulated in these nanoparticles. The resulting nanoparticle gel showed favorable mechanical properties for Argireline's skin delivery, offering better release regulation and enhanced permeation than the free peptide solution. Part II proposes the direct powder extrusion (DPE) 3D printing technique as a promising platform for manufacturing transdermal patches customized to individual patient needs. Ethylene Vinyl Acetate (EVA) copolymer was employed as the feedstock material for DPE, combined with model drugs possessing varied physicochemical properties. Notably, using the EVA grade with the appropriate vinyl acetate content enabled the successful printing of medications with different characteristics, while achieving the desired dose, release, and permeation profiles, marking a significant step forward for personalized medicine. Finally, in addressing wound healing, Part III introduces the solution blow spinning processing of keratin, extracted from wool wastes, into nano-fibrous patches that support tissue regeneration. The proposed strategy not only re-ennobled wool wastes into valuable biomedical material but also pioneered the spinning of keratin aqueous solutions, potentially allowing for the safe deposition of keratin patches directly onto the wound site. Furthermore, in vitro studies evaluating the hemocompatibility of the spun patches with human blood cells demonstrated their suitability for blood-contact applications. Overall, this thesis highlights the transformative potential of integrating emerging technologies, such as microfluidics, 3D printing, and solution blow spinning, into the development of advanced transdermal delivery and wound care systems. The research successfully addresses the limitations of established therapies by offering scalable, cost-efficient, and patient-centered alternatives.