Preparation and Characterization of Folate-Chitosan-Gemcitabine Core–Shell Nanoparticles for Potential Tumor-Targeted Drug Delivery

Abstract

For the purpose of achieving targeted chemotherapy of pancreatic cancer, we prepared core-shell nanoparticles by coaxial electrospray technology, with folate-chitosan as the polymeric coating material and gemcitabine as the encapsulated drug. The effects of various solution properties and processing parameters on nanoparticles formation were investigated. By optimizing the electrospray parameters, the diameter of the core-shell nanoparticles was in the range of 200-300 nm with drug loading and encapsulation efficiency of 3.91 +/- 0.12% and 85.37 +/- 4.9%. The drug release kinetics revealed a controlled initial burst release followed by a sustained release over a period of 72 h at pH 7.4 and pH 5.0, and at pH 5.0 the drug released more quickly. Moreover, the cellular uptake experiment confirmed that the folate conjugated core-shell nanoparticles had high pancreatic cancer (BXPC3) cells uptake efficiency. And the cell cytotoxicity test displayed that they had remarkable cytotoxicity towards BXPC3 cells. This study indicates that coaxial electrospray is a facile technique in producing core-shell nanoparticles encapsulating hydrophilic small molecule drugs, and clearly infers that the folate conjugated core-shell nanoparticles is very much effective to use as a pancreatic tumor-targeted delivery carrier for anticancer drugs.

Gemcitabine loaded biodegradable PLGA nanospheres for in vitro pancreatic cancer therapy

“…The use of novel nanomaterials for medical applications has recently been increased [7,8]. Different delivery strategies were attempted to treat pancreatic cancer using gemcitabine.…”

Preparation, Characterization, and Optimization of Folic Acid-Chitosan-Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery

“…These factors include effect of solvent properties (concentration, conductivity, surface tension, stability of the electrospray behavior, and interfacial surface tension between the inner and outer liquids), effect of applied voltage, needle diameters of core and shell solutions, ratio of flow rates between the core and shell solutions, and the distance between the nozzle and aluminum foil in which the latter one has already been studied (41,44,45,(51)(52)(53). Three independent factors like concentration, applied voltage, and ratio of flow rates between the core and shell solutions which can have the greatest impact on particle size were selected and studied further.…”

“…Based on these observations, the use of higher concentrations in the electrospray process makes it impossible. Thus, a concentration of 1 wt% would be desirable and best efficiency occurs at this level (51).…”

“…This evidence happened since the amino groups of chitosan were blocked in the conjugation process. Considering the experiences of others in this field, a solution of water/TFE/acetic acid, with ratios of 4:4:3 respectively was used as shell solvent (51,53).…”

“…These differences could be summarized into two main factors. The first one is NPs' structure decomposition in lower pH (51), and the second one might be due to the lower degree of MTX ionization under acidic medium (62). It is extremely important to avoid multidrug resistance (MDR) of initially sensitive tumor cells caused by slow release at the site of action by development of slow release to rapid release kinetics when the target sites have been reached (61).…”