Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

Abstract

This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.

Development of lattice-inserted 5-Fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system

“…20,25 Moreover, the peak at 601 cm -1 was attributed to the P-O-P stretching mode of PO 3À 4 . These absorption bands revealed the presence of the PO 4 3-group in the HAP structure. For 5FU, the absorption bands at 1726, 1670, and 1247 cm -1 are responsible for cyclic imide (CO-NH-CO), imide, amide I band (C ¼ O), and amide III band (C ¼ O), respectively.…”

Chitosan: poly(N-vinylpyrrolidone-alt-itaconic anhydride) nanocapsules—a promising alternative for the lung cancer treatment

“…Also, a type of polylactic acid nanoparticles loaded with docetaxel showed anti-metastatic effect on lung cancer cells (Anton et al 2008). 5-Fluorouracil (5-FU) is another chemotherapeutic drug which has been restricted by its systemic toxicities, severe gastrointestinal toxicities, hematologic side effects and severe bone marrow disturbances (Kalantarian et al 2010). Many studies demonstrated that 5-FU-loaded nanoparticles have a great potential for drug delivery and a good antitumor activity.…”

New Chitosan Nanospheres for the Delivery of 5-Fluorouracil: Preparation, Characterization and in vitro Studies

“…Moreover, tumor cells often undergo significant development of drug resistance. These problems lead to the need of high doses of 5-FU, so its use has been restricted by its systemic toxicities, as severe gastrointestinal toxicities, hematologic side effects and severe bone marrow disturbances [8].…”