Sustained drug release and cancer treatment by an injectable and biodegradable cyanoacrylate-based local drug delivery system

Abstract

Sustained drug release at specific sites is clinically favorable for the treatment of many diseases. The discovery of new polymeric materials suitable for prolonging drug release, improving therapeutic efficiency, and decreasing systemic toxicity is always of great interest in local sustained-release drug delivery systems (LSRDDSs). In this study, a new cross-linked cyanoacrylate (CA)-based LSRDDS is developed, in which the drug depot consists of a formulation of methoxyethyl cyanoacrylate (MOE-CA) with the cross-linking agent CA-PEG-CA. The MOE-CA endowed the CA polymer with good degradability. The drug-release profile could be affected by the structure and composition ratio of the MOE-CA/CA-PEG-CA monomer. The liquid CA monomer could dissolve the drug without using other solvents, and could polymerize into a solid glue just in a few seconds after injection. An optimal formulation loaded with 5-fluorouracil (J-Fu-1.25) showed excellent anticancer activity both in vitro and in vivo, with 50% survival of the mice and no significant systemic toxicity detected during the experiment. The CA depot might affect the blood flow in microvessels of tumors, thus contributing to the synergetic anticancer effect of 5-fluorouracil. We believe that this work provides a practical, biodegradable, and biocompatible LSRDDS for chemotherapeutic drug delivery that can also be applied universally with various drugs for certain therapeutic aims.