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Long-circulating lipoprotein-mimic nanoparticles for smart intravenous delivery of a practically-insoluble antineoplastic drug: Development, preliminary safety evaluations and preclinical pharmacokinetic studies.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2015 Sep 30; Vol. 493 (1-2), pp. 439-50. Date of Electronic Publication: 2015 Aug 04. - Publication Year :
- 2015
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Abstract
- 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 ± 2.17 nm). It possessed the highest negative zeta potential (-30.55 ± 0.24 mV) and the largest EE% (86.35 ± 2.33%). The significantly (P < 0.05) prolonged MRT(0-∞), longer elimination t50% and reduced plasma clearance highlighted the long-circulating characteristics of LP6. The preliminary safety evaluations and the seven-fold increase in bioavailability elucidated potentiality for smart intravenous delivery of CHL.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Intravenous
Animals
Antineoplastic Agents pharmacokinetics
Antineoplastic Agents pharmacology
Chlorambucil pharmacokinetics
Chlorambucil pharmacology
Drug Carriers pharmacokinetics
Drug Carriers pharmacology
Ear blood supply
Ear pathology
Hemolysis drug effects
Lecithins chemistry
Lipoproteins
Male
Nanoparticles chemistry
Rabbits
Rats, Wistar
Serum Albumin, Bovine chemistry
Antineoplastic Agents administration & dosage
Chlorambucil administration & dosage
Drug Carriers administration & dosage
Nanoparticles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 493
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 26253380
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2015.08.011