Ru Jiang

Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles

Paclitaxel (Taxol®) is an important anticancer drug in clinical use for treatment of a variety of cancers. Because of its low solubility, it is formulated in high concentration in Cremophor EL® which induces hypersensitivity reactions. In this study, targeted delivery of paclitaxel-loaded nanoparticles was prepared by a desolvation procedure, crosslinked on the wall material of bovine serum albumin, and subsequently decorated by folic acid. The characteristics of the nanoparticles, such as amount of folate conjugation, surface morphology, drug entrapment efficiency, drug loading efficiency, and release kinetics were investigated in vitro. The targeting effect was investigated in vitro by cancer cell uptake of fluorescein isothiocyanate-labeled nanoparticles. The spherical nanoparticles obtained were negatively charged with a zeta potential of about −30 mV, and characterized around 210 nm with a narrow size distribution. Drug entrapment efficiency and drug loading efficiency were approximately 95.3% and 27.2%, respectively. The amount of folate conjugation was 9.22 μg/mg of bovine serum albumin. The folate-decorated nanoparticles targeted a human prostate cancer cell line effectively.

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).

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 μM/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.

A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy.

Preparation and physicochemical properties of 10-hydroxycamptothecin (HCPT) nanoparticles by supercritical antisolvent (SAS) process.

The goal of the present work was to study the feasibility of 10-hydroxycamptothecin (HCPT) nanoparticle preparation using supercritical antisolvent (SAS) precipitation. The influences of various experimental factors on the mean particle size (MPS) of HCPT nanoparticles were investigated. The optimum micronization conditions are determined as follows: HCPT solution concentration 0.5 mg/mL, the flow rate ratio of CO2 and HCPT solution 19.55, precipitation temperature 35 °C and precipitation pressure 20 MPa. Under the optimum conditions, HCPT nanoparticles with a MPS of 180 ± 20.3 nm were obtained. Moreover, the HCPT nanoparticles obtained were characterized by Scanning electron microscopy, Dynamic light scattering, Fourier-transform infrared spectroscopy, High performance liquid chromatography-mass spectrometry, X-ray diffraction and Differential scanning calorimetry analyses. The physicochemical characterization results showed that the SAS process had not induced degradation of HCPT. Finally, the dissolution rates of HCPT nanoparticles were investigated and the results proved that there is a significant increase in dissolution rate compared to unprocessed HCPT.