title: Beta-casein and its complexes with chitosan as nanovehicles for delivery of a platinum anticancer drug.
abstract: The clinical application of platinum-based anticancer drugs is greatly limited by severe toxicity. Drug-delivery systems are much sought after to improve the efficacy and applicability of these drugs. Here, we describe a new drug-delivery system comprising a novel platinum complex (bipyridine morpholine dithiocarbamate Pt(II) nitrate) within nanoparticles composed of β-casein (β-CN) and chitosan (CS). The influence of pH on the formation of a colloidally-stable nanocarrier system composed of Pt complex-loaded β-CN and chitosan nanoparticles was investigated using UV-vis spectrometry, dynamic light scattering (DLS) and scanning electron microscopy (SEM). The particles of Pt complex-loaded beta-casein-chitosan formed were stable and soluble in the pH range 5.7-6.2. Hence, the optimal pH for complex formation is between the pI of casein (5.3) and the pKa of chitosan (6.5). DLS data showed that, at both pH values of 5.7 and 6.2, the particles formed had sizes between 200 and 300nm. However, the optimum pH for particle formation was pH 5.7. At this pH, the zeta-potential values of nanoparticles were positive and the particles were stable. SEM analysis confirmed the formation of nanoparticles with good colloidal stability and an average particle size of 200nm. The cytotoxicity of both free and encapsulated Pt complex was evaluated on colorectal carcinoma HCT116 cells. The results obtained indicated that both the cytotoxicity and cellular uptake of platinum were enhanced by its entrapment in β-CN-CS nanovehicles. These findings suggest that this novel drug-delivery system enables drugs to be thermodynamically stable in aqueous solutions and is potentially useful for targeted oral-delivery applications.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Razmi
authors.forename: Adeleh
authors.initials: A
authors.lastname: Divsalar
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboury
authors.forename: Zhila
authors.initials: Z
authors.lastname: Izadi
authors.forename: Thomas
authors.initials: T
authors.lastname: Haertlé
authors.forename: Hassan
authors.initials: H
authors.lastname: Mansuri-Torshizi
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D002364:Caseins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D003102:Colloids; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D045325:HCT116 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: C000589196:(bipyridine)(morpholine dithiocarbamate)platinum(II); D000970:Antineoplastic Agents; D002364:Caseins; D003102:Colloids; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D048271:Chitosan
keywords: Beta-casein; Chitosan; Nanovehicles; Oral drug-delivery system; Platinum complex