Research Articles
Poly(N‐vinyl‐pyrrolidone)‐block‐poly(D,L‐lactide) as polymeric emulsifier for the preparation of biodegradable nanoparticles

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ABSTRACT

Poly(D,L‐lactide) (PDLLA) amphiphilic block copolymers were employed as emulsifiers in the preparation of PDLLA nanoparticles by an oil/water emulsion solvent evaporation technique. The surface‐active properties of poly(N‐vinyl‐pyrrolidone)‐block‐poly(D,L‐lactide) (PVP‐b‐PDLLA) toward the biphasic system were compared to those of polyethylene glycol(PEG)‐b‐PDLLA of similar composition. PVP‐b‐PDLLA was found to be a suitable emulsifier for dichloromethane/water emulsions, yielding narrowly distributed nanoparticles (<250 nm) surrounded by a hydrophilic PVP corona. PEG‐b‐PDLLA, however, was only effective in producing appropriately sized nanoparticles when dichloromethane was replaced with ethyl acetate. Furthermore, the lyoprotectant properties of PVP allowed the freeze‐dried nanoparticles to recover their initial size following reconstitution, while PEG‐coated nanoparticles could not be redispersed following lyophilization. Two poorly water‐soluble drugs, that is, paclitaxel and etoposide, were efficiently loaded into PVP‐decorated PDLLA nanoparticles. The entrapment efficiency of etoposide was significantly enhanced by adding MgCl2 to the aqueous phase. It was found that the nanoparticles released the drugs progressively over several days in vitro. The obtained experimental results were corroborated with the theoretical compatibility between a given drug, polymer, and solvent, predicted by total solubility parameters. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1763–1775, 2007

Section snippets

INTRODUCTION

Amphiphilic block copolymers share a unique molecular structure, consisting of at least two polymer segments of dissimilar chemical natures. The composition of the repeat unit as well as the length of each block can be tailored to serve a variety of applications, including the preparation of micelles,1 vesicles,2 nano‐,3 and micro‐emulsions.4 They have also been utilized as stabilizers for organic pigments in aqueous media5 as well as for emulsion polymerization.6

In light of their tendency to

Materials

PDLLAs were purchased from PolySciences, Inc. (Warrington, PA) (Mn, 13400 (PI = 1.2), and 22,000 (PI = 1.6)) and Sigma‐Aldrich (St. Louis, MO) (Mn, 40,500 (PI = 1.8)). Their molecular weights were determined by size exclusion chromatography according to a method described elsewhere.14 PVP‐b‐PDLLA (Mn, 3500, 37.4% w/w LA) was synthesized according to a method previously reported.14 PEG‐b‐PDLLA (Mn, 3100, 35.5% w/w LA) was purchased from JCS Biopolytech, Inc. (Toronto, Ontario, Canada).

PVP‐b‐PDLLA as a Polymeric Surfactant

In this work, an o/w emulsion‐solvent evaporation method was applied to prepare PDLLA nanoparticles.23, 24 The organic phase was emulsified into an aqueous solution containing either PVP‐b‐PDLLA or PEG‐b‐PDLLA, of similar composition and molecular weight. The amphiphilic block copolymer served to stabilize the dispersed phase which contained PDLLA. Removal of the internal phase by rotary evaporation caused PDLLA to precipitate, yielding nanoparticles surrounded by either a PVP or a PEG corona.

CONCLUSION

In the present study, PVP‐b‐PDLLA was found to be an efficient emulsifier toward the DCM/water system. The block copolymer was thus employed in the preparation of sterically stabilized PDLLA nanoparticles by an o/w emulsion solvent evaporation method. Two poorly water‐soluble drugs were successfully incorporated into the nanoparticles and released over several days in vitro. Due to the presence of the PVP corona, the nanoparticles could be readily redispersed in aqueous media following

Acknowledgements

This work was supported financially by the Natural Sciences and Engineering Research Council of Canada. G. Gaucher acknowledges a scholarship from the Fonds de la Recherche en Santé du Québec. The authors thank Christine Allen (Faculty of Pharmacy, University of Toronto) for her help in determining the total solubility parameters. Marie‐Christine Jones and Marie‐Hélène Dufresne (Faculty of Pharmacy, University of Montreal) are acknowledged for their assistance in the preparation of the

REFERENCES (47)

  • W. Lu et al.

    Cationic albumin‐conjugated pegylated nanoparticles as novel drug carrier for brain delivery

    J Control Release

    (2005)
  • A. Malzert et al.

    Interfacial properties of adsorbed films made of a PEG2000 and PLA50 mixture or a copolymer at the dichloromethane‐water interface

    J Colloid Interface Sci

    (2003)
  • J. Liu et al.

    Polymer‐drug compatibility: A guide to the development of delivery systems for the anticancer agent, Ellipticine

    J Pharm Sci

    (2004)
  • J.H. Lee et al.

    Blood compatibility of polyethylene oxide surfaces

    Prog Polym Sci

    (1995)
  • A. Beletsi et al.

    Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA‐PEG diblock copolymers

    Int J Pharm

    (2005)
  • M. Shakweh et al.

    Poly(lactide‐co‐glycolide) particles of different physicochemical properties and their uptake by peyer's patches in mice

    Eur J Pharm Biopharm

    (2005)
  • Z. Zhang et al.

    Nanoparticles for poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: Synthesis, formulation, characterization and in vitro drug release

    Biomaterials

    (2006)
  • A. Kishida et al.

    Some determinants of morphology and release rate from poly(L)lactic acid microspheres

    J Control Release

    (1990)
  • I.A. Darwish et al.

    Effects of hydrophobic agents on the solubility, precipitation and protein binding of etoposide

    J Pharm Sci

    (1989)
  • T. Niwa et al.

    Preparations of biodegradable nanopspheres of water‐soluble and insoluble drugs with D,L‐lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and drug release behavior

    J Controlled Release

    (1993)
  • M. Brendel et al.

    The effect of salt and temperature on the infinite dilution activity coefficient of volatile organic chemicals in water

    Fluid Phase Equilib

    (1999)
  • R. Jeyanthi et al.

    Effect of solvent removal technique on the matrix characteristics of polylactide/glycolide microspheres for peptide delivery

    J Controlled Release

    (1996)
  • D.E. Discher et al.

    Polymer vesicles

    Science

    (2002)
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