In vitro and in vivo antitumor effect of gefitinib nanoparticles on human lung cancer

Abstract

Gefitinib (GEF) is the first epidermal growth factor receptor (EGFR)-targeting agent launched as an anticancer drug. It is an accepted opinion that modifying GEF strong hydrophobicity and poor bioavailability would not only enhance its antitumor effects, but also reduce its side effects. In this study, GEF-loadedpoly(e-caprolactone)-poly(ethyleneglycol)-poly(e-caprolactone) (PCEC) -bearing nanoparticles (GEF-NPs) were prepared by a solid dispersion method and characterized. The particle sizes increased with the increase in GEF/PCEC mass ratio in feed. GEF-NPs (10%) were mono-dispersed, smaller than 24 nm, zeta potential was approximately À18 mV, percentage encapsulation and loading, were more than 9% and 92%, respectively, and drug was slowly released but without a biphasic pattern. Microscopy studies of the optimized formulation confirmed that the prepared nanoparticles are spherical in nature. Cytotoxicity results indicated that cell growth inhibition induced by free GEF and GEF-NPs were dose and time dependent. Compared with free GEF, GEF-NPs enhanced antitumor effects, reduced side effects and significantly prolonged survival time in vivo. CD31, ki-67 and EGFR expression were significantly lower in the GEF-NPs group compared with other groups (p< .05). These findings demonstrated that GEF-NPs have the potential to attain superior outcomes and to overcome complications such as organs toxicity, therapeutic resistance and disease relapse. ARTICLE HISTORY

Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid&ndash;polymer hybrid nanoparticles

“…In vitro release behavior of PTX and TL from LPNs was explored by placing 1 mL of LPNs in dialysis bags (molecular weight cutoff, 3.5 kDa). 31 The dialysis bags were incubated in 30 mL phosphate buffer (pH, 7.4) containing Tween 80 (0.5%, w/w) at 37°C under gentle shaking (100 rpm). At different time intervals, incubation medium (2 mL) was taken out and replaced by the same volume of fresh preheated medium at specific time points.…”

Molecular Engineering of Ultrasmall Silica Nanoparticle–Drug Conjugates as Lung Cancer Therapeutics

“…In an effort to harness the unique characteristics of nanoparticles for drug delivery, attempts have been made to synthesize gefitinib-loaded nanoparticle constructs (Supplementary Table S1; refs. [29][30][31][32][33][34][35]. Unfortunately, these reports largely focus solely on in vitro cytotoxic effects, without investigation into their therapeutic potential in vivo (29)(30)(31)(32)35).…”

A novel radio-sensitization method for lung cancer therapy: enhanced radiosensitization induced by antigens/antibodies reaction after targeting tumor hypoxia using Bifidobacterium

“…The positive effects of this treatment were also assessed using 18 F-FDG PET/CT imaging. Several studies have shown that 18 F-FDG PET/CT can recognize early decreases in glucose metabolism that are associated with progression-free survival and overall survival in many cancers [25][26][27] . Unlike normal cells, the majority of the energy used by tumor cells relies on glycolysis, mediated by glycometabolic pathways as opposed to aerobic oxidation [28] .…”