Suggested procedures for the reproducible synthesis of poly(D,l-lactide-co-glycolide) nanoparticles using the emulsification solvent diffusion platform

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility. Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering). Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between-30 and +30 mV), with relatively narrow polydispersity. Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.

Original languageEnglish
Pages (from-to)448-453
Number of pages6
JournalCurrent Nanoscience
Volume14
Issue number5
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Drug delivery
  • Emulsion
  • Ethyl acetate
  • Nanoparticles
  • PLGA
  • Solvent diffusion

Cite this

@article{b52841f6d49542f0acd925f936ade8aa,
title = "Suggested procedures for the reproducible synthesis of poly(D,l-lactide-co-glycolide) nanoparticles using the emulsification solvent diffusion platform",
abstract = "Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility. Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability (<5{\%} variability in size (z-average) as determined by dynamic light scattering). Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between-30 and +30 mV), with relatively narrow polydispersity. Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.",
keywords = "Drug delivery, Emulsion, Ethyl acetate, Nanoparticles, PLGA, Solvent diffusion",
author = "Shadabul Haque and Boyd, {Ben J} and McIntosh, {Michelle P} and Pouton, {Colin W} and Kaminskas, {Lisa M} and Michael Whittaker",
year = "2018",
month = "1",
day = "1",
doi = "10.2174/1573413714666180313130235",
language = "English",
volume = "14",
pages = "448--453",
journal = "Current Nanoscience",
issn = "1573-4137",
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T1 - Suggested procedures for the reproducible synthesis of poly(D,l-lactide-co-glycolide) nanoparticles using the emulsification solvent diffusion platform

AU - Haque, Shadabul

AU - Boyd, Ben J

AU - McIntosh, Michelle P

AU - Pouton, Colin W

AU - Kaminskas, Lisa M

AU - Whittaker, Michael

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility. Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering). Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between-30 and +30 mV), with relatively narrow polydispersity. Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.

AB - Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsification-evaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsification-evaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility. Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability (<5% variability in size (z-average) as determined by dynamic light scattering). Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between-30 and +30 mV), with relatively narrow polydispersity. Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.

KW - Drug delivery

KW - Emulsion

KW - Ethyl acetate

KW - Nanoparticles

KW - PLGA

KW - Solvent diffusion

UR - http://www.scopus.com/inward/record.url?scp=85051401356&partnerID=8YFLogxK

U2 - 10.2174/1573413714666180313130235

DO - 10.2174/1573413714666180313130235

M3 - Article

VL - 14

SP - 448

EP - 453

JO - Current Nanoscience

JF - Current Nanoscience

SN - 1573-4137

IS - 5

ER -