pH-Responsive hydrogels containing PMMA nanoparticles: an analysis of controlled release of a chemotherapeutic conjugate and transport properties

Abstract

Biopolymers composed of a pH-responsive, hydrophilic poly(methacrylic acid-grafted-ethylene glycol) network polymerized in the presence of poly(methyl methacrylate) nanoparticles were designed for the oral delivery of chemotherapeutics for the treatment of colon cancer. An inulin–doxorubicin conjugate, designed to target the colon and improve doxorubicin efficacy, was loaded into these polymer carriers at an efficiency of 54%. Release studies indicated these polymer carriers minimized conjugate release in low pH conditions and released the conjugate at neutral pH conditions using a two-step pH experiment modeling the stomach and the small intestine. At lower concentration levels, the presence of the polymer carriers did not disrupt tight junctions as determined by transepithelial electrical resistance studies using Caco-2 and HT29-MTX cell lines which are an accurate model of the GI tract epithelia. Permeability values of unmodified doxorubicin and the inulin–doxorubicin conjugate in the presence of the polymer carriers were also determined using the same cell models and ranged from 1.87 to 3.80 × 10 ⁻⁶ cm/s.

Keywords:

• chemotherapeutics
• oral delivery
• permeability
• hydrogels
• nanoparticles
• controlled release

Acknowledgment

This research was supported by a grant from the NIH/NCI Center for Oncophysics (CTOPSOCU54-CA-143837). CAS acknowledges the National Science Foundation for a Graduate Research Fellowship.