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Start Over Author "Chen, Evan M" Publisher elsevier bv
17 results on '"Chen, Evan M"'

16. Biodegradable PEG-poly(ω-pentadecalactone-co-p-dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors

Author

Chen, Evan M., primary, Quijano, Amanda R., additional, Seo, Young-Eun, additional, Jackson, Christopher, additional, Josowitz, Alexander D., additional, Noorbakhsh, Seth, additional, Merlettini, Andrea, additional, Sundaram, Ranjini K., additional, Focarete, Maria Letizia, additional, Jiang, Zhaozhong, additional, Bindra, Ranjit S., additional, and Saltzman, W. Mark, additional

Published
2018
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17. Biodegradable PEG-poly(ω-pentadecalactone-co-p-dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors

Author

Ranjit S. Bindra, Young-Eun Seo, Seth Noorbakhsh, Evan M. Chen, Ranjini K. Sundaram, Alexander Josowitz, W. Mark Saltzman, Maria Letizia Focarete, Zhaozhong Jiang, Amanda Quijano, Christopher Jackson, Andrea Merlettini, Chen, Evan M., Quijano, Amanda R., Seo, Young-Eun, Jackson, Christopher, Josowitz, Alexander D., Noorbakhsh, Seth, Merlettini, Andrea, Sundaram, Ranjini K., Focarete, Maria Letizia, Jiang, Zhaozhong, Bindra, Ranjit S., and Saltzman, W. Mark

Subjects
Male, 0301 basic medicine, Drug, Radiation-Sensitizing Agents, Radiosensitizer, Polyesters, media_common.quotation_subject, Biophysics, Nanoparticle, Biocompatible Materials, Bioengineering, 02 engineering and technology, Pharmacology, Convection, Article, Polyethylene Glycols, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Drug Delivery Systems, PEG ratio, Animals, Distribution (pharmacology), media_common, Convection-enhanced delivery, Brain Neoplasms, Isoxazoles, 021001 nanoscience & nanotechnology, PEG, Intracranial, Xenograft Model Antitumor Assays, Rats, Inbred F344, Drug Liberation, 030104 developmental biology, chemistry, Mechanics of Materials, Pyrazines, Drug delivery, Hydrodynamics, Ceramics and Composites, Nanoparticles, Nanocarriers, 0210 nano-technology, Ethylene glycol
Abstract

Intracranial delivery of therapeutic agents is limited by penetration beyond the blood-brain barrier (BBB) and rapid metabolism of the drugs that are delivered. Convection-enhanced delivery (CED) of drug-loaded nanoparticles (NPs) provides for local administration, control of distribution, and sustained drug release . While some investigators have shown that repeated CED procedures are possible, longer periods of sustained release could eliminate the need for repeated infusions, which would enhance safety and translatability of the approach. Here, we demonstrate that nanoparticles formed from poly(ethylene glycol)-poly(ω-pentadecalactone- co-p -dioxanone) block copolymers [PEG-poly(PDL- co -DO)] are highly efficient nanocarriers that provide long-term release: small nanoparticles (less than 100 nm in diameter) continuously released a radiosensitizer (VE822) over a period of several weeks in vitro, provided widespread intracranial drug distribution during CED, and yielded significant drug retention within the brain for over 1 week. One advantage of PEG-poly(PDL-co -DO) nanoparticles is that hydrophobicity can be tuned by adjusting the ratio of hydrophobic PDL to hydrophilic DO monomers , thus making it possible to achieve a wide range of drug release rates and drug distribution profiles. When administered by CED to rats with intracranial RG2 tumors, and combined with a 5-day course of fractionated radiation therapy , VE822-loaded PEG-poly(PDL- co-DO) NPs significantly prolonged survival when compared to free VE822. Thus, PEG-poly(PDL-co-DO) NPs represent a new type of versatile nanocarrier system with potential for sustained intracranial delivery of therapeutic agents to treat brain tumors.

Published
2018

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