Multifunctional bio-inspired biomedical adhesive featuring fast-acting adhesion for topical drug delivery

Abstract

This report presents the synthesis and characterization of a new biomedical adhesive featuring fast-acting adhesion properties for potential application in topical drug delivery to localized areas. This new biomedical adhesive is synthesized through thermally initiated radical polymerization and consists of: (1) a mussel-inspired repeating unit (catechol), which provides strong biomedical adhesion, biocompatibility, and robust skin interactions, and (2) 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), an anionic repeat unit known for its biocompatibility, drug delivery capabilities, and electrostatic interactions. This combination leads to a multifunctional biomedical adhesive that offers fast-acting adhesion to the skin without the need for additional crosslinkers. The resulting copolymer, poly(2-acrylamido-2-methyl-1-propanesulfonic acid-co-N-methacryloyl 3,4-dihydroxyl-L-phenylalanine), further known as poly(AMPS-co-MDOPA), was tested both on PET films and porcine skin to quantify the adhesion properties and compare the setting times of the adhesive. A small amount (30 mg on dry PET surface, 100 mg on wet porcine skin) of adhesive was able to achieve a maximum strength of 105 kPa on a dry PET substrate in a lap shear strength test, and 3.1 kPa on wet porcine skin following only 5 minutes of application time. ¹H NMR was performed to confirm the chemical structure of the polymer, demonstrating successful synthesis with a repeating unit ratio of 88 : 12 for AMPS : MDOPA. The polymer showed no significant cytotoxicity when exposed to primary human dermal fibroblasts at modest concentrations, proving the polymers’ excellent biocompatibility. In separate tests, the new polymer demonstrated significantly lower cytotoxicity compared to a commercial sunscreen approved for use on human skin. In tests using proliferating human dermal fibroblast cells, the combination of the new poly(AMPS-co-MDOPA) (7.5 mg mL⁻¹) with sodium valproate (2 mM) effectively triggered cell death, demonstrating successful drug delivery. Due to high/fast-acting skin adhesion, soft nature, biocompatibility, and drug efficiency, this new copolymer shows great promise as a biomedical adhesive for skin tissue, offering a comfortable and efficient alternative to drug-containing topical ointments by extending the residence time of the drug at a localized skin site.