Fragmentation of Injectable Bioadhesive Hydrogels Affords Chemotherapeutic Macromolecules

Biomacromolecules. 2016 Aug 8;17(8):2634-41. doi: 10.1021/acs.biomac.6b00701. Epub 2016 Jul 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Humans
  • Hydrogels / chemistry*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Macromolecular Substances / chemistry*
  • Polymers / chemistry*
  • Serum Albumin, Bovine / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Hydrogels
  • Macromolecular Substances
  • Polymers
  • Serum Albumin, Bovine
  • Doxorubicin