In vitro and in vivo evaluation of novel NGR-modified liposomes containing brucine

Abstract

In this study, a novel NGR (Asn-Gly-Arg) peptide-modified liposomal brucine was prepared by using spray-drying method. The surface morphology of the liposomes, encapsulation efficiency and particle size were investigated. The data showed that the addition of NGR did not produce any significant influence on brucine liposomes in terms of particle size or zeta potential. In addition, after 3 months of storage, no dramatic change such as visible aggregation, drug content changes or precipitation in the appearance of NGR-brucine liposomes occurred. The in vitro release results indicated that the release of brucine from NGR liposomes was similar to that of liposomes, demonstrating that the NGR modification did not affect brucine release. The in vitro drug-release kinetic model of NGR-brucine liposomes fitted well with the Weibull’s equation. In vivo, NGR-brucine liposomes could significantly extend the bioavailability of brucine; however, there was no significant difference observed in the pharmacokinetic parameters between liposomes and NGR liposomes after intravenous administration. Antitumor activity results showed that NGR-modified liposomes exhibited less toxicity and much higher efficacy in HepG2-bearing mice compared with non-modified liposomes. The enhanced antitumor activity might have occurred because brucine was specifically recognized by NGR receptor on the surface of tumor cells, which enhanced the intracellular uptake of drugs.

Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles

“…Brucine (BRU) is a white, odorless, crystalline, and poorly water-soluble anticancer drug extracted from Strychnos nux-vomica seeds (Gupta & Chaphalkar, 2015 ). BRU is considered as a promising anticancer agent; it has antitumor activity, antiangiogenic effects, and anti-proliferative activity, therefore, can have anti-carcinogenic effects in different types of cancer (Shu & Xi-Peng, 2017 ). The current investigation is an attempt to incorporate BRU into PEG poly (lactic- co -glycolic acid) (PLGA) NPs to achieve passive targeting after intravenous administration.…”

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

“…This could also be taken as an evidence that ANP was successfully modified on the outer layer of the system. 35 Particle size is a key effect that can influence the in vivo distribution of carriers. The great advantages of nanosized carriers include prolonged blood circulation time and improved bioavailability.…”

Vasculogenic mimicry, a complex and devious process favoring tumorigenesis – Interest in making it a therapeutic target

“…The works do not specify the pharmacodynamic or pharmacokinetic characteristics of these molecules. For instance, brucine is weakly liposoluble (Li and Wang, 2017) and hardly crosses the barrier formed by the plasma and nuclear membranes. Also, if the pharmacological targets are intracellular, its availability may be limited.…”