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

Authors Sangi S, SreeHarsha N, Bawadekji A, Al Ali M

Received 8 May 2018

Accepted for publication 27 June 2018

Published 18 September 2018 Volume 2018:12 Pages 3051—3060


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Tuo Deng

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, targeting

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