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

Sibghatullah Sangi,1 Nagaraja SreeHarsha,2 Abdulhakim Bawadekji,3 Mouhanad Al Ali4 1Department of Clinical Pharmacy, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia; 2Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; 3Department of Biological Sciences, College of Science, Northern Border University, Arar, Saudi Arabia; 4Higher Institute of Health and Bio-products of Angers (ISSBA), Angers- France, Université d’Angers, Angers, France 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 µm, 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 µm. In vitro drug release studies revealed that ~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, t1/2(α) = 1.23 hours and t1/2(β) = 18.3 hours, was considerably longer than that of 5-FU, t1/2(α) = 0.34 hours and t1/2(β) = 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. Keywords: spray drying, 5-fluorouracil, cancer, microspheres, targetin