Pressure-sensitive adhesives are critical to the product's safety, efficacy, and quality in transdermal drug delivery systems. However, many defects of transdermal patches (e.g., insufficient adhesion, patch displacement, and "dark ring" phenomenon) remain. Herein, the N-[tris(hydroxymethyl)methyl]acrylamide (NAT)-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) (AA-NAT/Fe3+) was creatively proposed. Results demonstrated that the adhesiveness and cohesiveness of the optimized AA-NAT/Fe3+ were higher by 1.8- and 9.7-fold, respectively, than those of commercially available DURO-TAK® 87-4098 due to the hydrogen bonding interaction of NAT-skin interface and coordination of NAT-Fe3+. Moreover, compared with that of DURO-TAK® 87-4098, the adhesion time of AA-NAT/Fe3+ on the human forearm was remarkably prolonged, and no "dark ring" phenomenon was observed for AA-NAT/Fe3+ after removal. After clonidine (CLO) was loaded into AA-NAT/Fe3+, controlled drug release and a drug transdermal behavior were endowed for CLO@AA-NAT/Fe3+in vitro and in vivo. AA-NAT/Fe3+ still maintained superiority in adhesion and cohesion properties after CLO loading. These observations would contribute to the development of pressure-sensitive adhesives with outstanding adhesion and cohesion for transdermal patches. STATEMENT OF SIGNIFICANCE: This N-[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesive coordinated with Fe(III) has enhanced adhesion and cohesion properties, which provide a simple but effective strategy to solve the problems (e.g., insufficient adhesion, patch displacement, and "dark ring" phenomenon) in existing transdermal patches.
Keywords: Fe(3+)-coordinated strategy; Long-term skin adhesion; N-[tris(hydroxymethyl)methyl]acrylamide; Pressure-sensitive adhesives; Transdermal drug delivery.
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