Folate-mediated chondroitin sulfate-Pluronic ® 127 nanogels as a drug carrier

Abstract

Pluronic ® F127 (PF127), one of the polymers which can inhibit drug efflux transporters in cancer therapy, was used to produce amphiphilic nanocarriers for doxorubicin (DOX). In order to stabilize the nanocarriers, the hydroxyl groups on both termini of PF127 were acrylated and reacted with methacrylated chondroitin sulfate (CSMA) to form CS-PF127 nanogel. The introducing CSMA has carboxylic acid groups which can be used to react with a folic acid-polyethylene glycol (FA-PEG). Folic acid, having high binding affinity to tumor-associated folate receptors (FR), provides a selective delivery of doxorubicin (DOX) to FR-positive tumor cells. DOX was loaded either in a cationic DOX·HCl form through the electrostatic interactions with the negative charges of chondroitin sulfate, or in a free DOX form by solubilization into the PPO core compartment of PF127. The loading efficiency and release behavior of DOX prepared from two different formulations are compared. The synthesis of CS-PF127 and FA-PEG grafted CS-PF127 (FA-CS-PF127) was characterized by nuclear magnetic resonance spectrometry (NMR), ultraviolet/visible spectroscopy (UV), and X-ray photoelectron spectroscopy (XPS). With a fluorescent probe technique, the critical aggregation concentrations (CAC) are 7.5 × 10 −2 mg/mL for CS-PF127 and 7.9 × 10 −2 mg/mL for FA-CS-PF127, respectively. The spherical images of nanogels were visualized with the use of the transmission electron microscope (TEM). The particle diameters measured by dynamic light scattering (DLS) are 299.6 ± 8.2 nm for CS-PF127 and 138.3 ± 12.3 for FA-CS-PF127, neither aggregation nor change in sizes in double deionized (DD) water after 20 days. The better cellular uptake of FA-CS-PF127 in KB cells was evidenced by confocal laser scanning microscopy (CLSM) and flow cytometry upon loading Rhodamine123 as a probe.