Cellular evaluation of oral chemotherapy carriers.
Hydrogel nanospheres composed of methacrylic acid and poly(ethylene glycol) were loaded with bleomycin and tested as a potential oral delivery system for chemotherapeutic agents. The gastrointestinal epithelium was modeled through the use of Caco-2 monolayers for studies of permeation enhancement by the carriers as well as bleomycin transport. Bleomycin efficacy following release from the carrier was evaluated with a DLD-1 tumor cell model. The nanospheres release bleomycin in response to a pH increase similar to that seen when passing from the stomach into the upper small intestine. These carriers can also increase the permeability of a model of the epithelial barrier, which would hopefully improve drug transport into the bloodstream. Efficacy studies using a tumor cell model showed retention of activity for bleomycin following loading and release from the nanospheres. The carriers described performed well during in vitro evaluation and can hopefully expand the spectrum of chemotherapeutic agents capable of being administered orally.
Blanchette
James
J
Department of Biomedical Engineering, University of Texas at Austin, Austin Texas 78712-0231, USA.
Peppas
Nicholas A
NA
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001692:Biological Transport; D001761:Bleomycin / Q000008:administration & dosage; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D043942:Nanotubes; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011109:Polymethacrylic Acids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D020100:Hydrogels; D011109:Polymethacrylic Acids; C099679:poly(methacrylic acid-ethylene glycol); D001761:Bleomycin; D011092:Polyethylene Glycols