title: A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.
abstract: 5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53±1.65 mg/L(*)h vs 7.80±0.83 and 5.82±0.83 mg/L(*)h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Hongru
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Pi
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China; Department of Pharmacy, The First Affiliated Hospital of Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Sichuan Medical University, Luzhou, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010316:Particle Size; D011817:Rabbits; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D005472:Fluorouracil
keywords: 5-fluorouracil; distribution; ethyl cellulose; hollow microspheres; pharmacokinetics; polyvinyl pyrrolidone