Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment.
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.
Particle Design Research Group, Faculty of Pharmacy, Shah Alam, Selangor 40450, Malaysia; Non-Destructive Biomedical and Pharmaceutical Research Centre, Puncak Alam, Selangor 42300, Malaysia.
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Particle Design Research Group, Faculty of Pharmacy, Shah Alam, Selangor 40450, Malaysia; Non-Destructive Biomedical and Pharmaceutical Research Centre, Puncak Alam, Selangor 42300, Malaysia.
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Particle Design Research Group, Faculty of Pharmacy, Shah Alam, Selangor 40450, Malaysia; Non-Destructive Biomedical and Pharmaceutical Research Centre, Puncak Alam, Selangor 42300, Malaysia; CoRe Frontier Materials and Industry Application, Universiti Teknologi MARA, Puncak Alam, Selangor 42300, Malaysia. Electronic address: wongtinwui@salam.uitm.edu.my.
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D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004127:Dimethylhydrazines; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010368:Pectins / Q000737:chemistry; D011208:Powders; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D004127:Dimethylhydrazines; D011208:Powders; D013608:Tablets, Enteric-Coated; C013517:ethyl cellulose; D010368:Pectins; D002482:Cellulose; D005472:Fluorouracil
5-Fluorouracil; Colon cancer; Colon-specific drug delivery; In vivo pellet coating