Cytotoxicity and antitumour activity of 5-fluorouracil-loaded polyhydroxybutyrate and cellulose acetate phthalate blend microspheres.
Pharmacokinetics, biodistribution and antitumour activity of 5-fluorouracil (5-FU)-loaded polyhydroxybutyrate (PHB) and cellulose acetate phthalate (CAP) blend microspheres were investigated in chemically induced colorectal cancer in albino male Wistar rats and compared with pristine 5-FU given as a suspension. The microspheres were characterised for particle size, encapsulation efficiency, in vitro release and in vitro cytotoxicity on human HT-29 colon cancer cell line. Spherical particles with a mean size of 44 ± 11 µm were obtained that showed sustained release of 5-FU. A high concentration of 5-FU was achieved in colonic tissues and significant reduction in tumour volume and multiplicity were observed in animals treated with 5-FU-loaded microspheres. The decreased levels of plasma albumin, creatinine, leucocytopenia and thrombocytopenia were observed in animals for 5-FU microspheres compared to the standard 5-FU formulation. The results suggest the extended release of 5-FU from the PHB-CAP blend microspheres in colonic region to enhance the antitumour efficacy.
Department of Pharmacology, Soniya Education Trust's College of Pharmacy, Sangolli Rayanna Nagar, Dharwad 580002, Karnataka, India.
Kiran
K
Chaturvedi
Santosh Kumar
SK
Tripathi
Anandrao R
AR
Kulkarni
Tejraj M
TM
Aminabhavi
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000091402:Prohibitins; D051381:Rats; D017208:Rats, Wistar; D000094122:Polyhydroxybutyrates
D000964:Antimetabolites, Antineoplastic; D002482:Cellulose; D004337:Drug Carriers; D005472:Fluorouracil; D006885:Hydroxybutyrates; D011091:Polyesters; D000091402:Prohibitins; C000717328:PHB protein, human; C000717332:Phb protein, rat; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates; C011708:cellulose acetate phthalate