Solid Tumor Chemotherapy and in Vivo Distribution of Fluorouracil Following Administration in Poly(L-Lactic Acid) Microspheres

Abstract

The physicochemical properties and in vivo distribution of poly(L-lactide) (L-PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent evaporation method were evaluated for potential use in the treatment of liver cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da) and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean particle size of the microspheres was 3-6 microns, and there was a direct relationship between the mean particle size and the molecular weight of the polymers. The drug release behavior from microspheres exhibited a diffusion mechanism in different dissolution media, with the molecular weight of the polymer being a major factor in controlling the drug release and degradation rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in the liver. The disappearance rate of radioactivity from the tissue was very slow in comparison to that of free 5-FU. The results were confirmed by histological examination of liver tissue following administration of fluorescein particles. In addition, growth of a human liver tumor as first transplant generation under the renal capsule of immunocompetent rats and antitumor activity of L-PLA2 microspheres were investigated. Histological examination by optical microscopy showed that there was no neoplastic tissue of the kidney or in other tissues examined after treatment.

Effects of chemical and physical parameters in the generation of microspheres by hydrodynamic flow focusing

“…Despite these procedures, the powders produced are often of poor quality, exhibit broad distributions in shape and size, and often contain electrostatic charges which were introduced during the milling process [9]. More control is gained over size, shape, and active component distribution (e.g., drug) with the methods of spray drying [10], solvent evaporation/emulsification [11,12], phase separation [11,13], and rapid freeze drying [14]. An additional advantage of these methods for the preparation of drug-loaded microspheres, and particularly of the freeze drying method, is their high throughput.…”

FIESTA: An MR arthrography celebration of shoulder joint anatomy, variants, and their mimics

“…5‐Fluorouracil (5‐FU) has been one of the most effective chemotherapeutic agents with clinical activity against squamous esophageal carcinoma,12–15 which is the dominant pathological form of esophageal cancer 16–18. It acts mainly through the inhibition of synthesis of DNA during the S‐phase of the cell cycle 19.…”

In Vivo Evaluation of 5-Fluorouracil-Containing Self-Expandable Nitinol Stent in Rabbits: Efficiency in Long-Term Local Drug Delivery

“…5-Fluorouracil (5-FU) has been one of the most effective chemotherapeutic agents with clinical activity against squamous esophageal carcinoma, [12][13][14][15] which is the dominant pathological form of esophageal cancer. [16][17][18] It acts mainly through the inhibition of synthesis of DNA during the S-phase of the cell cycle.…”