PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies.

Abstract

The objective of the present study was to incorporate the hydrophilic anti-cancer drug 5-Fluorouracil(5-FU) into poly(lactide-co-glycolide) (PLGA) nanoparticles(NP) to improve the oral bioavailability. Owing to the high solubility of 5-FU in basic water, the water-in-oil-in-water (w/o/w) emulsification process has been chosen as one of the most appropriate method for the encapsulation of 5-FU, and the ammonia solution was used as the inner aqueous phase solvent to increase the solubility of 5-FU. In order to reach submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, we prepared 5-FU loaded PLGA-NP by a high-pressure emulsification-solvent evaporation process. The PLGA-NPs were characterized with respect to their morphology, particle size, size distribution, 5-FU encapsulation efficiency, in vitro and in vivo studies in rats. In vitro release of 5-FU from nanoparticles appeared to have two components with an initial rapid release due to the surface associated drug and followed by a slower exponential release of 5-FU, which was dissolved in the core. The in vivo research was studied in male Sprague-Dawley rats after an oral 5-FU dose of 45 mg/kg. Single oral administration of 5-FU loaded PLGA-NP to rats produced bioavailability, which was statistically higher than 5-FU solution as negative control. And the MRT (mean residence time) of 5-FU loaded PLGA-NP was significantly (P < 0.05) modified. Thus, it is possible to design a controlled drug delivery system for oral 5-FU delivery, improving therapy efficiency by possible reduction of time intervals between peroral administrations and reduction of local gastrointestinal side effects.

• Authors: XueMing Li, YuanLong Xu, GuoGuang Chen, Ping Wei, QiNeng Ping
• Journal: Drug development and industrial pharmacy (Drug Dev Ind Pharm) Vol. 34 Issue 1 Pg. 107-15 (Jan 2008) ISSN: 0363-9045 [Print] England
• PMID: 18214762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Delayed-Action Preparations
• Drug Carriers
• Emulsions
• Polymers
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Fluorouracil

Topics

• Administration, Oral
• Animals
• Antimetabolites, Antineoplastic (administration & dosage, chemistry, pharmacokinetics)
• Area Under Curve
• Biological Availability
• Delayed-Action Preparations
• Dose-Response Relationship, Drug
• Drug Carriers
• Emulsions
• Fluorouracil (administration & dosage, chemistry, pharmacokinetics)
• Half-Life
• Lactic Acid (chemistry)
• Male
• Nanoparticles
• Particle Size
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polymers (chemistry)
• Rats
• Rats, Sprague-Dawley
• Solubility
• Technology, Pharmaceutical (methods)