Back to Search
Start Over
Effective cellular internalization, cell cycle arrest and improved pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles
- Source :
- International journal of pharmaceutics. 543(1-2)
- Publication Year :
- 2017
-
Abstract
- The present study aims at the development of cholesterol based lipopolymeric nanoparticles for improved entrapment, better cell penetration and improved pharmacokinetics of Tamoxifen (TMX). Self-assembling cholesterol grafted lipopolymer, mPEG-b-(CB-{g-chol}-co-LA) was synthesized from poly(ethyleneglycol)-block-2-methyl-2-carboxyl-propylenecarboxylic acid-co-poly (l-lactide) [mPEG-b-(CB-{g-COOH}-co-LA)] copolymer followed by carbodiimide coupling for attaching cholesterol. Lipopolymeric nanoparticles were prepared using o/w solvent evaporation technique, which were subsequently characterized to determine its particle size, entrapment efficiency, release pattern and compared with mPEG-PLA nanoparticles. Further, in order to assess the in vitro efficacy, cytotoxicity studies, uptake, apoptosis assay and cell cycle analysis were performed in breast cancer cell lines (MCF-7 and 4T1). Finally, the pharmacokinetic profile of TMX loaded mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles was also performed. TMX loaded lipopolymeric nanoparticles of particle size 151.25 ± 3.74 (PDI 0.123) and entrapment efficiency of 73.62 ± 3.08% were formulated. The haemolytic index, protein binding and in vitro drug release of the optimized nanoparticles were found to be comparable to that of the TMX loaded mPEG-PLA nanoparticles. Lipopolymeric nanoparticles demonstrated improved IC50 values in breast cancer cells (22.2 μM in 4T1; 18.8 μM in MCF-7) than free TMX (27.6 μM and 23.5 μM respectively) and higher uptake efficiency. At IC50 values, TMX loaded lipopolymeric nanoparticles induced apoptosis and cell cycle arrest (G0/G1 phase) to similar extent as that of free drug. Pharmacokinetic studies indicated ∼2.5-fold increase in the half-life (t1/2) (p < 0.001) and ∼2.7-fold (p < 0.001) increase in the mean residence time (MRT) of TMX following incorporation into lipopolymeric nanoparticles. Thus, mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles offer a more promising approach for delivery of Tamoxifen in breast cancer by improving drug internalization and prolonging the mean residence time of the drug indicating possibility of dose reduction and hence bypassing the adverse effects of TMX therapy.
- Subjects :
- Erythrocytes
Antineoplastic Agents, Hormonal
Cell Survival
media_common.quotation_subject
Polyesters
Pharmaceutical Science
Nanoparticle
Apoptosis
02 engineering and technology
010402 general chemistry
01 natural sciences
Hemolysis
Polyethylene Glycols
chemistry.chemical_compound
Mice
Pharmacokinetics
Cell Line, Tumor
Animals
Humans
Internalization
Cytotoxicity
media_common
Carbodiimide
Drug Carriers
Chemistry
Estrogen Antagonists
Biological Transport
Cell Cycle Checkpoints
021001 nanoscience & nanotechnology
In vitro
0104 chemical sciences
Drug Liberation
Tamoxifen
Cholesterol
Biophysics
Nanoparticles
0210 nano-technology
Drug carrier
Subjects
Details
- ISSN :
- 18733476
- Volume :
- 543
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- International journal of pharmaceutics
- Accession number :
- edsair.doi.dedup.....a7be6db8d913929c0084923dd2060b8a