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Evaluation of pharmacokinetic and pharmacodynamic profiles of liposomes for the cell type-specific delivery of small molecule drugs.
- Source :
-
Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2017 Nov; Vol. 13 (8), pp. 2565-2574. Date of Electronic Publication: 2017 Jul 25. - Publication Year :
- 2017
-
Abstract
- Liposome-based drug formulations represent an exciting avenue of research as they increase efficacy to toxicity ratios. Current formulations rely on passive accumulation to the disease site where drug is taken up by the cells. Ligand mediated targeting increases the net accumulation of liposomes, however, an unexplored benefit is to potentially refine pharmacodynamics (PD) of a drug specifically to different cell types within diseased tissue. As a model system, we engineered cardiomyocyte- (I-1) and endothelial-targeted (B-40) liposomes to carry a VEGFR2 inhibitor (PTK787), and examined the effect of cell type-specific delivery on both pharmacokinetics (PK) and PD. Neovascularization in post-myocardial infarction was significantly reduced by B-40 liposomes loaded with PTK787 as compared to animals injected with I-1 liposomes, and profoundly more as compared to free PTK787. This study thus shows that the intraorgan targeting of drugs through cell type-specific delivery holds substantial promise towards lowering the minimal efficacious dose administered systemically.<br /> (Published by Elsevier Inc.)
- Subjects :
- Animals
Drug Delivery Systems
Mice
Myocardial Infarction complications
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic etiology
Peptide Library
Phthalazines pharmacokinetics
Phthalazines therapeutic use
Protein Kinase Inhibitors pharmacokinetics
Protein Kinase Inhibitors therapeutic use
Pyridines pharmacokinetics
Pyridines therapeutic use
Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
Liposomes chemistry
Peptides chemistry
Phthalazines administration & dosage
Protein Kinase Inhibitors administration & dosage
Pyridines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1549-9642
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Nanomedicine : nanotechnology, biology, and medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28754465
- Full Text :
- https://doi.org/10.1016/j.nano.2017.07.005