Abstract
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 (d50) 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 (IC50) 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.
Highlights
According to the 2018 report of the World Health Organization (WHO), lung cancer, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related human death worldwide
Zhu et al used a co-matrix of poly(lactic-co-glycolic acid) (PLGA) and D-tocopherol polyethylene glycol (1000) succinate (TPGS) to control the release rate, enhance encapsulation efficiency, and the antitumor effect of docetaxel [14]. These findings suggest that the combination of PLGA and functional polymers may be a suitable strategy to achieve efficient delivery of antitumor drugs
We systematically evaluated the physicochemical properties of the newly developed GFB/FCPPNEMs, including morphology, particle size distribution (PSD), crystalline state, drug loading amount, Fourier transform infrared (FT-IR) spectrum, drug release profiles, and release mechanism
Summary
According to the 2018 report of the World Health Organization (WHO), lung cancer, non-small cell lung cancer (NSCLC), is the leading cause of cancer-related human death worldwide. In this study, we sought to develop such a novel type of FCPP-NEM carrier system to achieve effective lung tumor-targeted delivery, pH-responsive sustained release, facilitated cellular uptake, and enhanced antitumor effects of the antitumor drugs, like gefitinib. To achieve this goal, we systematically evaluated the physicochemical properties of the newly developed GFB/FCPPNEMs, including morphology, particle size distribution (PSD), crystalline state, drug loading amount, Fourier transform infrared (FT-IR) spectrum, drug release profiles, and release mechanism. An accelerated stability study was conducted to determine the physicochemical stability of GFB/FCPP-NEMs
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