Open AccessFragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules
Author(s) -
Yuji Yamada,
Joel P. Schneider
Publication year - 2016
Publication title -
biomacromolecules
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.689
H-Index - 220
eISSN - 1526-4602
pISSN - 1525-7797
DOI - 10.1021/acs.biomac.6b00701
Subject(s) - chemistry , bioadhesive , bovine serum albumin , doxorubicin , biophysics , drug delivery , cytotoxicity , macromolecule , liberation , conjugate , self healing hydrogels , polymer chemistry , chromatography , in vitro , biochemistry , organic chemistry , surgery , chemotherapy , biology , medicine , mathematical analysis , mathematics
Implantation of drug delivery depots into or proximal to targeted tissue is an effective method to deliver anticancer drugs in a sustained localized manner. Herein, syringe-injectable polydextran aldehyde (PDA)-based bioadhesive gels are prepared that can locally deliver cytotoxins upon their hydrolytic fragmentation. Adhesive gels are formed by mixing doxorubicin (DOX)-functionalized PDA (DOX-PDA) and bovine serum albumin (BSA) using a dual-barrel syringe. Upon mixing and delivery, the DOX-PDA reacts with the cross-linker BSA as well as the extracellular matrix via imine bond formation to define the cohesive and adhesive properties of the gel, respectively. Resulting gels are mechanically rigid (∼10 kPa) and adherent (adhesive stress ∼ 4 kPa). Once formed, the DOX-PDA-BSA gels undergo slow hydrolytic degradation (>2 months) locally releasing free DOX and DOX-PDA as expected. Surprisingly, we found that macromolecules composed of DOX, PDA, and BSA are also released from the bulk material. These DOX-PDA-BSA macromolecules, along with free DOX and DOX-PDA conjugate, are internalized by A549 lung carcinoma cells, resulting in potent cell death.