Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment
| Autor: | Anirbandeep Bose, Tin Wui Wong, A. Elyagoby |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adenoma
Drug Antimetabolites Antineoplastic Colorectal cancer Chemistry Pharmaceutical media_common.quotation_subject Pellets Administration Oral Biological Availability Pharmaceutical Science Adenocarcinoma Pharmacology Rats Sprague-Dawley Drug Delivery Systems Aberrant Crypt Foci Pharmacokinetics In vivo medicine Animals Technology Pharmaceutical Cellulose media_common Dimethylhydrazines Chemistry digestive oral and skin physiology Capsule medicine.disease digestive system diseases Tumor Burden Bioavailability Solubility Colonic Neoplasms Feasibility Studies Pectins Female Fluorouracil Tablets Enteric-Coated Powders Aberrant crypt foci |
| Zdroj: | International Journal of Pharmaceutics. 468:178-186 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2014.04.006 |
| Popis: | In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach. |
| Databáze: | OpenAIRE |
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