Residual polyvinyl alcohol associated with poly (D,L-lactide-co-glycolide) nanoparticles affects their physical properties and cellular uptake

Sanjeeb K. Sahoo, Jayanth Panyam, Swayam Prabha, Vinod Labhasetwar

Research output: Contribution to journalArticlepeer-review

819 Scopus citations

Abstract

Polyvinyl alcohol (PVA) is the most commonly used emulsifier in the formulation of poly lactide and poly (D,L-lactide-co-glycolide) (PLGA) polymeric nanoparticles. A fraction of PVA remains associated with the nanoparticles despite repeated washing because PVA forms an interconnected network with the polymer at the interface. The objective of this study was to determine the parameters that influence the amount of residual PVA associated with PLGA nanoparticles and its effect on the physical properties and cellular uptake of nanoparticles. Nanoparticles were formulated by a multiple emulsion-solvent evaporation technique using bovine serum albumin (BSA) as a model protein. The parameters that affected the amount of residual PVA include the concentration of PVA and the type of organic solvent used in the emulsion. The residual PVA, in turn, influenced different pharmaceutical properties of nanoparticles such as particle size, zeta potential, polydispersity index, surface hydrophobicity, protein loading and also slightly influenced the in vitro release of the encapsulated protein. Importantly, nanoparticles with higher amount of residual PVA had relatively lower cellular uptake despite their smaller particle size. It is proposed that the lower intracellular uptake of nanoparticles with higher amount of residual PVA could be related to the higher hydrophilicity of the nanoparticle surface. In conclusion, the residual PVA associated with nanoparticles is an important formulation parameter that can be used to modulate the pharmaceutical properties of PLGA nanoparticles.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalJournal of Controlled Release
Volume82
Issue number1
DOIs
StatePublished - Jul 18 2002

Bibliographical note

Funding Information:
Grant support from the National Institutes of Health (HL 57234) and the Nebraska Research Initiative, Gene Therapy Program. JP is supported by a pre-doctoral fellowship from the American Heart Association and SP by a pre-doctoral fellowship (DAMD-17-02-1-0506) from Department of Army, the US Army Medical Research Association Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014. We thank Ms Elaine Payne for providing administrative support.

Keywords

  • Hydrophobicity
  • Intracellular uptake
  • Particle size
  • Polyvinyl alcohol
  • Sustained release

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