Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

Youngme Lee, Eric Sah, Hongkee Sah

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Abstract: The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60–150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5–4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms. Graphical Abstract: Schematic illustration of an innovative chemical approach to solvent removal during nanoencapsulation. Methyl propionate present in the aqueous continuous phase reacts with sodium hydroxide, thereby producing methanol and sodium propionate. Its alkaline hydrolysis allows the continuous extraction of the solvent out of nanoemulsion droplets, eventually solidifying them into nanoparticles. It is a simple but effective nanoencapsulation technique that has advantages over typical solvent evaporation and/or extraction methods. [Figure not available: see fulltext.]

Original languageEnglish
Article number453
Pages (from-to)1-12
Number of pages12
JournalJournal of Nanoparticle Research
Issue number11
StatePublished - 1 Nov 2015

Bibliographical note

Funding Information:
This study was supported by the Korea SGER Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2014R1A1A2A16054899).

Publisher Copyright:
© 2015, Springer Science+Business Media Dordrecht.


  • Drug delivery
  • Nanoencapsulation
  • Nanomedicine
  • Nanoparticles
  • Poly(lactide-co-glycolide)
  • Solvent removal


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