Key result
TPGS-emulsified paclitaxel nanoparticles achieve ~37% lower IC50 against coronary smooth muscle cells versus standard paclitaxel.
Why the study?
Paclitaxel has poor solubility and side effects limiting its clinical use for restenosis treatment, motivating development of effective delivery nanoparticles.
Do TPGS-emulsified paclitaxel-loaded PLGA nanoparticles improve cellular uptake and cytotoxicity compared to PVA-emulsified nanoparticles and Taxol in coronary artery smooth muscle cells?
Do TPGS-emulsified paclitaxel-loaded PLGA nanoparticles improve cellular uptake and cytotoxicity compared to PVA-emulsified nanoparticles and Taxol in coronary artery smooth muscle cells?
Absolute Event Rate: 474% vs 748%
TPGS-emulsified PLGA nanoparticles enhance the delivery and antiproliferative efficacy of paclitaxel in coronary artery smooth muscle cells, showing promise for future nanoparticle-coated stents.
Enhanced cytotoxicity supports TPGS-emulsified nanoparticle development for stents; hypothesis-generating and requires in vivo validation before clinical consideration.
AIMS: Paclitaxel is one of the most effective antiproliferative agents and it has been applied in the development of drug-eluting stents. There are difficulties, however, in using paclitaxel in clinical applications owing to its poor solubility and side effects. We have synthesized nanoparticles of biodegradable polymers for the effective and sustainable delivery of paclitaxel and other antiproliferative agents for restenosis treatment. METHODS & RESULTS: Paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a modified solvent extraction/evaporation method with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) or polyvinyl alcohol (PVA) as an emulsifier. Drug-loaded nanoparticles were characterized for size and size distribution, surface morphology, surface charge, drug-encapsulation efficiency and in vitro drug-release kinetics. Cellular uptake of fluorescent nanoparticles was investigated in vitro in coronary artery smooth muscle cells and in vivo in the carotid arteries of rabbits. The antiproliferative effects of the nanoparticle formulations were assessed in vitro in close comparison with Taxol((R)). Both the PVA- and TPGS-emulsified nanoparticles have similar size and size distribution, surface morphology and dispersion stability and showed great advantages over paclitaxel in in vitro cellular uptake and cytotoxicity than Taxol. The TPGS-emulsified nanoparticle formulation has higher drug-encapsulation efficiency, cellular uptake and cytotoxicity than the PVA-emulsified nanoparticle formulation. IC(50) in 24-h culture with coronary artery smooth muscle cells is 748 ng/ml for paclitaxel, 708 ng/ml for PVA-emulsified nanoparticles and 474 ng/ml for TPGS-emulsified nanoparticles, respectively. CONCLUSION: TPGS-emulsified PLGA nanoparticles have great potential for the effective and sustainable delivery of antiproliferative agents and for the development of nanoparticle-coated stents, which may become the third generation of cardiovascular stents.
No takes yet. Share an insight, caveat, or question.
Feng et al. (2007) studied Cardiovascular restenosis. TPGS-emulsified paclitaxel-loaded PLGA nanoparticles vs. Paclitaxel (Taxol) and PVA-emulsified nanoparticles was evaluated on IC50 in 24-h culture with coronary artery smooth muscle cells. TPGS-emulsified paclitaxel-loaded nanoparticles demonstrated higher cytotoxicity against coronary artery smooth muscle cells (IC50 474 ng/ml) compared to paclitaxel (748 ng/ml) and PVA-emulsified nanoparticles (708 ng/ml).
Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context: