In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer

Abstract

Background: Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogentargeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin. Methods: Four kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice. Results:The ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin. Conclusion:In this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic.

Application of nanotechnology in the early diagnosis and comprehensive treatment of gastrointestinal cancer

“…It also significantly increased the metabolic times of drugs in blood circulation, increased drug accumulations in tumour sites, and reduced drug toxicity (Fig. 7) [160]. Exosomes are small vesicles containing complex RNA and protein.…”

Novel 5-Fluorouracil Carbonate-Loaded Liposome: Preparation, In Vitro, and In Vivo Evaluation as an Antitumor Agent

“…The pharmacokinetic (PK) study of LipoXL-01 was conducted in healthy ICR mice (male, 6 weeks old, 20–22 g) . Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was employed for analysis of plasma samples.…”

“…The pharmacokinetic (PK) study of LipoXL-01 was conducted in healthy ICR mice (male, 6 weeks old, 20−22 g). 36 Liquid chromatography-tandem mass spectrometry (LC− MS/MS) was employed for analysis of plasma samples. The pharmacokinetic parameters of LipoXL-01 and 5-FU, such as the elimination half-life (t 1/2 ), the maximum plasma concentration (C max ), the area under the plasma concentration−time curve (AUC), clearance, mean residence time (MRT), and the apparent volume of distribution (V d ), were calculated by the noncompartmental method using the Phoenix WinNonlin 6.4 pharmacokinetic program (Pharsight Corporation, Cary, NC).…”

Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia

“…Currently, liposome is the most widely used in clinical. 24 , 25 Liposomal doxorubicin is the first nanodrug approved by FDA in 1995. 24 Liposomes composition is similar to biofilm, and it has excellent biocompatibility and metabolic properties.…”

“…Such as, polyethylene glycol (PEG) increases oxaliplatin-nanoparticles prolonged circulation time, and promotes accumulation at the gastric tumor area. 25 The p-aminophenyl-α-D-manno-pyranoside (MAN) and agglutinin modified liposome could markedly improve the transport of epirubicin and resveratrol across the BBB and the survival of brain tumor-bearing animals. 29 Phosphatidylethanolamines and dioleoylphosphatidylethanolamine based nanoliposomes are more sensitive to the acid environment of cerebral ischemic penumbra.…”