Long-circulating lipoprotein-mimic nanoparticles for smart intravenous delivery of a practically-insoluble antineoplastic drug: Development, preliminary safety evaluations and preclinical pharmacokinetic studies

[Display omitted] Chlorambucil (CHL) is a water-insoluble antineoplastic drug having a short elimination half-life. It suffers from remarkable differences in pharmacokinetics following oral administration. The current work aimed to assess safety and pharmacokinetics of CHL-loaded, lipoprotein-mimic,...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2015-09, Vol.493 (1-2), p.439-450
Main Authors: Tadros, Mina Ibrahim, Al-mahallawi, Abdulaziz Mohsen
Format: Article
Language:English
Subjects:
Administration, Intravenous
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Bovine serum albumin
Chlorambucil
Chlorambucil - administration & dosage
Chlorambucil - pharmacokinetics
Chlorambucil - pharmacology
Drug Carriers - administration & dosage
Drug Carriers - pharmacokinetics
Drug Carriers - pharmacology
Ear - blood supply
Ear - pathology
Egg yolk lecithin
Hemolysis - drug effects
Intravenous delivery
Lecithins - chemistry
Lipoprotein-mimic nanoparticles
Lipoproteins
Male
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Rabbits
Rats, Wistar
Serum Albumin, Bovine - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] Chlorambucil (CHL) is a water-insoluble antineoplastic drug having a short elimination half-life. It suffers from remarkable differences in pharmacokinetics following oral administration. The current work aimed to assess safety and pharmacokinetics of CHL-loaded, lipoprotein-mimic, nanoparticles (NPs) following intravenous administration. The design of NPs was based on complexation between egg yolk lecithin (EYL) and bovine serum albumin (BSA). The NPs were preliminary evaluated via FT-IR, DSC and P-XRD. The NPs were characterized for particle size, zeta potential, morphology and drug entrapment efficiency (EE%). The best achieved NP dispersion (LP6) and CHL solution were challenged for in vitro hemolytic potential, in vivo vascular irritation studies in rabbits and in vivo pharmacokinetics following intravenous administration in rats. The results confirmed that NPs were stabilized by hydrophobic-attractions and hydrogen-bondings between CHL, BSA and EYL. The amorphous dispersion of CHL within NPs was revealed. LP6 dispersion displayed monodispersed nano-spherical particles (144.33±2.17nm). It possessed the highest negative zeta potential (−30.55±0.24mV) and the largest EE% (86.35±2.33%). The significantly (P
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2015.08.011