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In this study, a new kind of folic acid (FA)-conjugated and chitosan (CS)-coated poloxamer 407 (P407)/poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs), FCPP NPs, were prepared, and further micro-encapsulated by carboxymethyl β-glucan microcapsules (MCs) to produce a multifunctional system of NPs embedded in MCs (NEMs) for potential lung tumor-targeted delivery of gefitinib. The prepared gefitinib-loaded FCPP (GFB/FCPP) NPs showed a hydrodynamic diameter of 255.4 ± 14.5 nm and existed in an amorphous state. After encapsulation in carboxymethyl β-glucan MCs, the GFB/FCPP-based NEMs (GFB/FCPP-NEMs) also exhibited a spherical morphology with a median diameter (d 50 ) of around 2.2 μm. After hydration, GFB/FCPP- NEMs can quickly dissociate into its primary particles, GFB/FCPP NPs. Our in vitro drug release study revealed that these GFB/FCPP-NEMs exhibited a pH-responsive prolonged release property. In addition, the cellular uptake study demonstrated that FCPP-NEMs serve as an efficient carrier to enhance the delivery of the entrapped drug into the target lung tumor cells. Moreover, the GFB/FCPP-NEMs induced a superior cytotoxic effect compared with free gefitinib. The inhibitory concentration to achieve 50% cell death (IC 50 ) of GFB/FCPP-NEMs in A549 cells was 3.82-fold lower than that of free gefitinib. According to these results, FCPP-NEMs hold a great potential as a multifunctional and high-performance biomaterial for lung tumor targeting delivery, pH-responsive sustained release, facilitated cellular uptake, and enhanced antitumor effect of antitumor drugs, like gefitinib.

pharmaceutics

Development and Evaluation of Multifunctional Poly(Lactic-co-glycolic acid) Nanoparticles Embedded in Carboxymethyl β-Glucan Porous Microcapsules as a Novel Drug Delivery System for Gefitinib