Optimization of the preparation process of vinblastine sulfate (VBLS)-loaded folate-conjugated bovine serum albumin (BSA) nanoparticles for tumor-targeted drug delivery using response surface methodology (RSM). 2009

Yuangang Zu, and Yu Zhang, and Xiuhua Zhao, and Qi Zhang, and Yang Liu, and Ru Jiang
Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin, Heilongjiang, China. zygorl@yahoo.com.cn

Response surface methodology (RSM) was used to optimize the process of preparing bovine serum albumin (BSA) nanoparticles by desolvation, then the resulting BSA nanoparticles (BSANPs) were conjugated with folate to produce a drug carrier system that can specifically target tumors. The anticancer drug, vinblastine sulfate (VBLS), was loaded to this tumor-specific drug carrier system for the purpose of overcoming the nonspecific targeting characteristics and side effects of the drug. A central composite design was applied for modeling the process, which was composed of four independent variables, namely BSA concentration, the rate of adding ethanol (ethanol rate), ethanol amount, and the degree of crosslinking. The mean particle size and residual amino groups of the BSANPs were chosen as response variables. The interactive effects of the four independent variables on the response variables were studied. The characteristics of the nanoparticles; such as amount of folate conjugation, drug entrapment efficiency, drug-loading efficiency, surface morphology and release kinetics in vitro were investigated. Optimum conditions for preparing desired BSANPs, with a mean particle size of 156.6 nm and residual amino groups of 668.973 nM/mg, were obtained. The resulting folate-conjugated BSANPs (FA-BSANPs) showed a drug entrapment efficiency of 84.83% and drug-loading efficiency of 42.37%, respectively, and the amount of folate conjugation was 383.996 microM/g BSANPs. The results of this study indicate that using FA-BSANPs as a drug carrier system could be effective in targeting VBLS-sensitive tumors in the future.

UI MeSH Term Description Entries
D008422 Materials Testing The testing of materials and devices, especially those used for PROSTHESES AND IMPLANTS; SUTURES; TISSUE ADHESIVES; etc., for hardness, strength, durability, safety, efficacy, and biocompatibility. Biocompatibility Testing,Biocompatible Materials Testing,Hemocompatibility Testing,Testing, Biocompatible Materials,Testing, Hemocompatible Materials,Hemocompatibility Testings,Hemocompatible Materials Testing,Materials Testing, Biocompatible,Materials Testing, Hemocompatible,Testing, Biocompatibility,Testing, Hemocompatibility,Testing, Materials,Testings, Biocompatibility
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D003460 Crystallization The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Crystalline Polymorphs,Polymorphism, Crystallization,Crystal Growth,Polymorphic Crystals,Crystal, Polymorphic,Crystalline Polymorph,Crystallization Polymorphism,Crystallization Polymorphisms,Crystals, Polymorphic,Growth, Crystal,Polymorph, Crystalline,Polymorphic Crystal,Polymorphisms, Crystallization,Polymorphs, Crystalline
D004058 Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially FACILITATED DIFFUSION, is a major mechanism of BIOLOGICAL TRANSPORT. Diffusions
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D005492 Folic Acid A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. Pteroylglutamic Acid,Vitamin M,Folacin,Folate,Folic Acid, (D)-Isomer,Folic Acid, (DL)-Isomer,Folic Acid, Calcium Salt (1:1),Folic Acid, Monopotassium Salt,Folic Acid, Monosodium Salt,Folic Acid, Potassium Salt,Folic Acid, Sodium Salt,Folvite,Vitamin B9,B9, Vitamin

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