Abstract
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.
Highlights
Transdermal drug delivery is an attractive alternative to parenteral administration
GRAPHICAL ABSTRACT | Highly controlled intradermal delivery can be performed with multi-compartmental polymer microneedles that are able to indent the skin and be implanted in it with a fast dissolving tip and a slow degradable body made of porous PLGA μPs
To cross the skin barrier imposed by the stratum corneum, the outermost lipophilic layer of the skin, which only allows the transport of molecules of fewer than 400 Da (Schaefer et al, 1997, 2011; Naik et al, 2000; Bouwstra and Ponec, 2006)
Summary
Transdermal drug delivery is an attractive alternative to parenteral administration. It bypasses the hepatic first-pass metabolism, preventing intestinal degradation and reducing systemic drug exposure (Kumar and Philip, 2007; Chu et al, 2010; Nguyen et al, 2018). To cross the skin barrier imposed by the stratum corneum, the outermost lipophilic layer of the skin (thickness of 10–30 μm), which only allows the transport of molecules of fewer than 400 Da (Schaefer et al, 1997, 2011; Naik et al, 2000; Bouwstra and Ponec, 2006) Several techniques, such as microdermabrasion, laser ablation, radiofrequency, and thermal abrasion, are used to enhance skin permeability (Kumar and Philip, 2007). Microneedle-based technology has attracted the attention of the cosmetic industry for skin aging, acne, photodamage, and hyperpigmentation treatment (Preetha and Karthika, 2009)
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