Fe(III)-coordinated N-[tris(hydroxymethyl)methyl]acrylamide-modified acrylic pressure-sensitive adhesives with enhanced adhesion and cohesion for efficient transdermal application

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/Fe 3+ ) was creatively proposed. Results demonstrated that the adhesiveness and cohesiveness of the optimized AA-NAT/Fe 3+ 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-Fe 3+ . Moreover, compared with that of DURO-TAK® 87-4098, the adhesion time of AA-NAT/Fe 3+ on the human forearm was remarkably prolonged, and no “dark ring” phenomenon was observed for AA-NAT/Fe 3+ after removal. After clonidine (CLO) was loaded into AA-NAT/Fe 3+ , controlled drug release and a drug transdermal behavior were endowed for CLO@AA-NAT/Fe 3+ in vitro and in vivo . AA-NAT/Fe 3+ 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.