title: Cisplatin loaded albumin mesospheres for lung cancer treatment.
abstract: The low solubility of cisplatin in aqueous solution limits the treatment effectiveness and the application of cisplatin in various kinds of drug-eluting devices. Although cisplatin has a high solubility in Dimethyl sulfoxide (DMSO), the toxicity of cisplatin can be greatly reduced while dissolved in DMSO. In this study, the solid powder of cisplatin-loaded albumin mesospheres (CDDP/DMSO-AMS), in a size range of 1 to 10 µm, were post-loaded with cisplatin and showed high cisplatin content (16% w/w) and effective cytotoxicity to lung cancer cells. Cisplatin were efficiently absorbed into the albumin mesospheres (AMS) in DMSO and, most importantly, the toxicity of cisplatin was remained at 100% after the loading process. This CDDP/DMSO-AMS was designed for the intratumoral injection through the bronchoscopic catheter or dry powder inhalation (DPI) due to its high stability in air or in solution. This CDDP/DMSO-AMS showed a fast cisplatin release within 24 hours. In the in vitro study, CDDP/DMSO-AMS showed high effectiveness on killing the lung cancer cells including the non-small cell lung cancer (NCL-H23 and A549), malignant mesothelioma (CRL-2081) and the mouse lung carcinoma (Lewis lung carcinoma) cell lines. The albumin based mesospheres provide an ideal loading matrix for cisplatin and other metal-based drugs due to the high swelling degree and fast uptake rate in the organic solvents with high polarity. In addition, to investigate the effects of polysaccharides, such as chitosan and chondroitin, on enhancing loading efficiency and lasting cytotoxicity of cisplatin, the polysaccharide-modified albumin mesospheres were synthesized and loaded with cisplatin in this study.
authors.affiliation: Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida P. O. Box 100225, Gainesville, FL 32611-6400, USA ; Biomaterials Center, Department of Materials Sciences and Engineering, University of Florida P. O. Box 116400, Gainesville, FL 32611-6400, USA.
authors.forename: Hung-Yen
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida P. O. Box 100225, Gainesville, FL 32611-6400, USA ; NF/SGVHS, Malcom Randall VA Medical Center, University of Florida P. O. Box 100225, Gainesville, FL 32611-6400, USA.
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
authors.affiliation: Biomaterials Center, Department of Materials Sciences and Engineering, University of Florida P. O. Box 116400, Gainesville, FL 32611-6400, USA.
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Goldberg
authors.affiliation: Hematology and oncology, University of Florida P. O. Box 116400, Gainesville, FL 32611-6400, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Kaye
authors.affiliation: Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Florida P. O. Box 100225, Gainesville, FL 32611-6400, USA ; NF/SGVHS, Malcom Randall VA Medical Center, University of Florida P. O. Box 100225, Gainesville, FL 32611-6400, USA.
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
keywords: Cis-diamminedichloroplatinum (II); DMSO; albumin mesospheres; chitosan; chondroitin; cytotoxicity; non-small cell lung cancer (NSCLC)