Unknown

Dataset Information

0

Evaluation of pharmacokinetic and pharmacodynamic profiles of liposomes for the cell type-specific delivery of small molecule drugs.


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.

SUBMITTER: Dasa SSK 

PROVIDER: S-EPMC5673558 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Evaluation of pharmacokinetic and pharmacodynamic profiles of liposomes for the cell type-specific delivery of small molecule drugs.

Dasa Siva Sai Krishna SSK   Suzuki Ryo R   Mugler Emily E   Chen Lanlin L   Jansson-Löfmark Rasmus R   Michaëlsson Erik E   Lindfors Lennart L   Klibanov Alexander L AL   French Brent A BA   Kelly Kimberly A KA  

Nanomedicine : nanotechnology, biology, and medicine 20170725 8


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)  ...[more]

Similar Datasets

| S-EPMC6113056 | biostudies-literature
| S-EPMC8079196 | biostudies-literature
| S-EPMC3995748 | biostudies-literature
| S-EPMC7424591 | biostudies-literature
| S-EPMC2190000 | biostudies-other
| S-EPMC7468263 | biostudies-literature
| S-EPMC6815719 | biostudies-literature
| S-EPMC5971577 | biostudies-literature
| S-EPMC4068583 | biostudies-literature
| S-EPMC7828117 | biostudies-literature