Chemotherapeutic drug targeting to lungs by way of microspheres after intravenous administration.

Purpose: Currently, microsphere technology plays a major role in the development of many new cancer therapies. In the current study, we proposed a targeted drug-delivery system to improve the treatment efficacy of one of the common conventional chemotherapeutic drugs used to treat lung tumors, 5-fluorouracil (5-FU). Materials and methods: Following the preparation and optimization of small, solid microspheres, ranging in diameter between 5 and 15 mu m, the final product 5-fluorouracil gelatin (5-FUG) was formulated using a Buchi Nano Spray Dryer by varying the drug:polymer ratio. Results: Particle yield was calculated as 65% +/- 1.2%, and the drug content in the formulation was recorded as 74% +/- 1.6%. Particle surface morphology was examined as shriveled shape (crumpled/folded); particle size distribution displayed a binomial distribution, with a mean diameter of 9.6 pm. In vitro drug release studies revealed that similar to 36.4% of the 5-FU in 5-FUG was released in the first hour after injection. Clinically, this would lead to initial or burst release, facilitating a quick rise to therapeutic levels. In contrast to the pure 5-FU drug (89.2% of the drug released in the first 30 minutes), 99.1% of the drug in 5-FUG was released from the spray-dried particles for a period of 12 hours. A two-compartment model was used to generate plasma concentration-time curves. 5-FUG injection has a much different distribution in vivo in contrast to intravenous injection of 5-FU. In addition, the half-life after intravenous injection of 5-FUG, t(1/2)(alpha) = 1.23 hours and t(1/2)(beta)= 18.3 hours, was considerably longer than that of 5-FU, t(1/2)(alpha)= 0.34 hours and t(1/2)(beta)= 8.62 hours. Examination of stained lung tissue sections showed no histopathological tissue changes or evidence of gross pathology. In addition, the optimized formulation demonstrated an increased stability under both long-term and refrigerated storage conditions. Conclusion: Our goal was to develop similar delivery systems for other chemotherapeutic drugs that are site specific to different disease models/tumor types.