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Targeting normal and neoplastic tissues in the rat jejunum and colon with boronated, cationic acrylamide copolymers.

Abstract
A series of boronated cationic copolymers, composed of different ratios of acrylamide, N-acryloyl-3-aminophenylboronic acid and N-acryloyl-diaminoethane (the cationic moiety), were prepared with the intention of localizing boron neutron capture therapy (BNCT) in experimentally induced polyps on the luminal side of the gut of the rat. The goals of this study were to: (a) test the effect of cationization of the boronated copolymers on their uptake by polyps and normal adjacent epithelium; (b) compare the whole rat body distribution of aminophenylboronic acid (APB) and polymeric APB after local application; (c) measure the effect of micro-environmental parameters such as pH, the presence of mucin and cations on the interaction between the APB-copolymers and the epithelium of the rat intestines. Direct analysis of tissue boron levels showed that polymeric APB-uptake was higher in the colonic polyps than in the surrounding normal tissues. Free APB, however, was found in similar quantities in both. When tested in the normal jejunum and colon of the rat, polymeric APB uptake was directly proportional to the molar content of the cationic monomer in the copolymers. The presence of magnesium ions, free boron cationic monomer and mucin interfered with this uptake in a concentration-dependent manner. The uptake was pH-independent at pH 5, 7 and 10. APB accumulation in the colon polyps was inversely proportional to the cationic monomer content in the copolymers, suggesting an increased amount of mucus around the polyps, which probably impeded the electrostatic attachment of the polymer to the malignant tissue. The use polymeric APB for targeting BNCT in perioperative treatment of colorectal carcinoma is suggested, especially in the cases of microscopic residual disease after curative resection.
AuthorsAbdel-Kareem Azab, Morris Srebnik, Victoria Doviner, Abraham Rubinstein
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 106 Issue 1-2 Pg. 14-25 (Aug 18 2005) ISSN: 0168-3659 [Print] Netherlands
PMID16005094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Boronic Acids
  • Carcinogens
  • Cations
  • Drug Carriers
  • Mucins
  • Polymers
  • Tissue Adhesives
  • Acrylamide
  • 3-aminobenzeneboronic acid
  • 1,2-Dimethylhydrazine
  • Boron
Topics
  • 1,2-Dimethylhydrazine (pharmacology)
  • Acrylamide (chemistry)
  • Animals
  • Boron (chemistry, pharmacokinetics)
  • Boron Neutron Capture Therapy
  • Boronic Acids (chemistry, pharmacokinetics)
  • Carcinogens (pharmacology)
  • Cations
  • Colon (drug effects, metabolism)
  • Colonic Neoplasms (chemically induced, metabolism)
  • Drug Carriers
  • Intestinal Mucosa (drug effects, metabolism)
  • Jejunum (drug effects, metabolism)
  • Mucins (metabolism)
  • Polymers (chemical synthesis, pharmacokinetics)
  • Rats
  • Rats, Inbred Strains
  • Tissue Adhesives

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