5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

Abstract

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47 +/- 11 and 67 +/- 12 microg 5-FU mg(-1) microspheres and the percentage of entrapment efficiency was between 52 +/- 12 and 74 +/- 13. Microspheres were of small size (average diameter: 0.9 +/- 0.4-1.4 +/- 0.8 microm microspheres without drug; 1.1 +/- 0.5-1.7 +/- 0.9 microm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger Tg. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of Tg of the polymer of the microspheres. The presence of 5-FU did not modify the Tg values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28-129 h) was in the order PLA > PLGA 75/25 > PLGA 50/50. A burst effect (17-20%) was observed during the first hour and then a period of constant release rate (3.52 +/- 0.82-1.46 +/- 0.26 microg 5-FU h(-1) per milligram of microspheres) up to 8 or 13 h, depending on the polymer, was obtained.

Preparation of 5‐Fluorouracil‐Poly(L‐lactide) Microparticles Using Solution‐Enhanced Dispersion by Supercritical CO2

“…One way to increase the therapeutic efficacy of the drugs is to encapsulate them in sustained delivery systems by using biodegradable polymers. [1] In general, the 5-Fu-sustained delivery systems are generated by an emulsion solvent evaporation technique (or modified versions of), [2][3][4][5] emulsion polymerization, [6] and spray-drying methods. [1,7] However, in these processes, an additional drying step is required to reduce the residual solvents, while removal of residual solvents to very low concentrations is important to ensure a safe and stable microparticle product.…”

Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads

“…In addition, dry beads are more fragile and susceptible to shear stress from rotating paddles. 5,25 The formulation N 1 (free from CaCO 3 ), because of more effective entrapment of drug in the highly dense external structure of alginate, exhibited a slow and extended release of 1.35 ± 0.038 mg/h and t 80% = 21.64 hours, but these beads were nonbuoyant. The gas-forming agent was added in varying amounts to make these beads float in the medium.…”

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

“…PLGA was suitable for sustainedrelease of 5-FU when 5-FU was suspended in PLGA organic solvents and the drug surface was coated with PLGA. [36][37][38][39][40] To obtain sustained-release of 5-FU, 5-FU-HAGS was made with a piece of hemostatic absorbable gelatin sponge (2.5 cm × 1 cm) which fully absorbed a suspension of 1 mL of 10% PLGA EA solution containing 20 mg of 5-FU (the particle size of the drug was 5.3 ± 1.2 µm). The suspension was made by vortex mixing for 10 minutes and was absorbed completely by the hemostatic absorbable gelatin sponge after 5 minutes.…”

“…5-FU was quantified by ultraviolet-visible (UV-Vis) spectroscopy. 36 5-FU-HAGS were incubated in vials containing 3 mL of phosphate-buffered saline ([PBS] 100 mM, pH 7.4) at 37°C with constant shaking at the rate of 150 rpm. For 5-FU release, the release medium was replaced with fresh buffer on a scheduled date and the content of 5-FU was measured by UV/Vis spectroscopy.…”