Microfluidic Manufacturing of SN-38-Loaded Polymer Nanoparticles with Shear Processing Control of Drug Delivery Properties.
Mol Pharm
; 16(1): 96-107, 2019 01 07.
Article
em En
| MEDLINE
| ID: mdl-30477300
ABSTRACT
Two-phase gas-liquid microfluidic reactors provide shear processing control of SN-38-loaded polymer nanoparticles (SN-38-PNPs). We prepare SN-38-PNPs from the block copolymer poly(methyl caprolactone- co-caprolactone)- block-poly(ethylene oxides) (P(MCL- co-CL)- b-PEO) using bulk and microfluidic methods and at different drug-to-polymer loading ratios and on-chip flow rates. We show that, as the microfluidic flow rate ( Q) increases, encapsulation efficiency and drug loading increase and release half times increase. Slower SN-38 release is obtained at the highest Q value ( Q = 400 µL/min) than is achieved using a conventional bulk preparation method. For all SN-38-PNP formulations, we find a dominant population (by number) of nanosized particles (<50 nm) along with a small number of larger aggregates (>100 nm). As Q increases, the size of aggregates decreases through a minimum and then increases, attributed to a flow-variable competition of shear-induced particle breakup and shear-induced particle coalescence. IC25 and IC50 values of the various SN-38-PNPs against MCF-7 cells show strong flow rate dependencies that mirror trends in particle size. SN-38-PNPs manufactured on-chip at intermediate flow rates show both minimum particle sizes and maximum potencies with a significantly lower IC25 value than the bulk-prepared sample. Compared to conventional bulk methods, microfluidic shear processing in two-phase reactors provides controlled manufacturing routes for optimizing and improving the properties of SN-38 nanomedicines.
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Base de dados:
MEDLINE
Assunto principal:
Polímeros
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Sistemas de Liberação de Medicamentos
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Microfluídica
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Nanopartículas
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Irinotecano
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Canadá