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.

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.

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.