Development, In Vitro Characterization, and In Vivo Toxicity Evaluation of Chitosan-Alginate Nanoporous Carriers Loaded with Cisplatin for Lung Cancer Treatment.

Abstract

Polysaccharide-based aerogels are promising drug carriers. Being nanoporous with a high specific surface area allows their use as a drug vehicle for various delivery routes. Intratracheal and intravenous administration of free cisplatin causes toxicity in the rat liver, lungs, and kidneys. In this work, microspherical particles based on alginate-chitosan without a traditional crosslinker were evaluated for targeted delivery of cisplatin by intratracheal administration. The aerogel particles were prepared using the emulsion gelation method, followed by supercritical carbon dioxide extraction. Loading of cisplatin on the prepared porous particles was performed by impregnation using supercritical fluid technology. The prepared carrier and the loaded drug were evaluated for drug content, release, and in vivo acute and subacute toxicity. Cisplatin was successfully loaded (percent drug loading > 76%) on the prepared carrier (particle size = 0.433 ± 0.091μm) without chemically interacting with the carrier and without losing its crystal form. Sixty percent of cisplatin was released within 2h, and the rest was loaded inside the polymer pores and had a sustained first-order release over 6h. Loading cisplatin on the carrier developed herein reduced the cisplatin lung toxicity but increased the liver toxicity after intratracheal administration with nephrotoxicity being proportional to cisplatin dose in case of carrier-loaded cisplatin. Moreover, loading cisplatin on the carrier significantly reduced mortality rate and prevented weight loss in rats as compared to free cisplatin in subacute studies after intratracheal administration. Thus, the developed carrier showed high potential for targeted delivery of cisplatin for lung cancer treatment by inhalation. Graphical abstract.