Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

Abstract

Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA nanoparticles are a feasible carrier for endostar. Endostar-loaded PEG-PLGA nanoparticles seem to have a better anticancer effect than conventional endostar. We believe that PEG-PLGA nanoparticles are an effective carrier for protein medicines.

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

“…17 Among them, poly(lactide-co-glycolide) (PLGA, 50:50 approved by the US Food and Drug Administration) has been used in the preparation of a wide variety of drug delivery systems, because it is biodegradable, biocompatible, capable of controlling the release of the incorporated entity at specific target sites and shows low toxicity. 18,19 Moreover, these colloidal systems are able to extravasate solid tumors, in which the capillary endothelium is defective. 20,21 We have devised an approach for loading bioactive catechins from black tea (theaflavin, TF) and green tea (epigallocatechin-3-gallate, EGCG) in a PLGA carrier so that their uptake, retention, and cytotoxicity in cancer cells can be enhanced in vitro and in vivo.…”

Preparation of endostatin-loaded chitosan nanoparticles and evaluation of the antitumor effect of such nanoparticles on the Lewis lung cancer model

“…Methods, such as the preparation of PEGylated ES (Tong et al, 2010), ES microsphere (Wu et al, 2009) and ES-loaded NPs have been used to try to overcome these shortcomings. Although ES-loaded PEG-PLGA (Hu & Zhang, 2010) and PLA NPs were reported previously, in this work, we have prepared new ES NPs, named ES-NPs, and evaluated their characteristics and antitumor effects.…”

Interaction of cancer cells with magnetic nanoparticles modified by methacrylamido-folic acid

“…Many conventional cancer chemotherapies are ineffective because of an inability to reach the tumor site in effective concentrations. 1 There is little doubt that nanoparticles offer new opportunities in many fields. 2 Nanotechnology is expected to revolutionize medicine.…”