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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(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-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 −18 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 timein 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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). Anin vitrorelease test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES + PTX, and ES-NPs + PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profilein vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs + PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs + PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to prepare ES-loaded chitosan nanoparticles (ES-NPs) and evaluate the antitumor effect of these particles on the Lewis lung cancer model. ES-NPs were prepared by a simple ionic cross-linking method. The characterization of the ES-NPs, including size distribution, zeta potential, loading efficiency and encapsulation efficiency (EE), was performed. Anin vitrorelease test was also used to determine the release behavior of the ES-NPs. Cell viability and cell migration were assayed to detect thein vitroantiangiogenic effect of ES-NPs. In order to clarify the antitumor effect of ES-NPsin vivo, the Lewis lung cancer model was used. ES-NPs were successfully synthesized and shown to have a suitable size distribution and high EE. The nanoparticles were spherical and homogeneous in shape and exhibited an ideal releasing profilein vitro. Moreover, ES-NPs significantly inhibited the proliferation and migration of human umbilical vascular endothelial cells (HUVECs). Thein vivoantiangiogenic activity was evaluated by ELISA and immunohistochemistry analyses, which revealed that ES-NPs had a stronger antiangiogenic effect for reinforced anticancer activity. Indeed, even the treatment cycle in which ES-NPs were injected every seven days, showed stronger antitumor effect than the free ES injected for 14 consecutive days. Our study confirmed that the CS nanoparticle is a feasible carrier for endostatin to be used in the treatment of lung cancer. [ABSTRACT FROM AUTHOR]