Oral chemotherapeutic delivery: design and cellular response.
The development of carriers to deliver a variety of cancer therapeutics orally would represent a significant advance in the treatment of this disease. This system is based on hydrophilic polymer carriers to deliver therapeutic agents to the upper region of the small intestine in response to the pH increase when passing from the stomach. Methacrylic acid (MAA) and ethylene glycol (EG) combined in a 1:1 molar ratio were reacted to form P(MAA-g-EG) nanospheres by UV-initiated free radical polymerization. Bleomycin was added prior to polymerization to allow in situ polymerization loading. Release studies were carried out in conditions to model the environment of the stomach and small intestine. Results showed that bleomycin is preferentially released at a higher pH due to the increased mesh size of the swollen hydrogel carrier. The potential cytotoxicity of bleomycin on the small intestine was investigated with the use of Caco-2 cells (human colon adenocarcinoma). Cytotoxicity studies showed maintenance of both viability and proliferation. The presence of the nanospheres decreases the transepithelial electrical resistance across Caco-2 cell monolayers. Complexation hydrogels are promising carriers to expand the number of chemotherapeutics capable of being administered orally.
Blanchette
James
J
Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712-0231, USA.
Peppas
Nicholas A
NA
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001761:Bleomycin / Q000008:administration & dosage*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D015195:Drug Design; D005766:Gastrointestinal Contents / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D019904:Polymethyl Methacrylate / Q000737:chemistry*
D000970:Antineoplastic Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D001761:Bleomycin; D011092:Polyethylene Glycols; D019904:Polymethyl Methacrylate