Structural rearrangements of polymeric insulin-loaded nanoparticles interacting with surface-supported model lipid membranes

Rickard Frost, Christian Grandfils, Bernardino Cerda, Bengt Kasemo, Sofia Svedhem

.

DOI: 10.4236/jbnb.2011.22023                

Abstract

The design and screening of nanoparticles for therapeutic applications (nanodrugs) belong to an emerging research area, where surface based analytical techniques are promising tools. This study reports on the interaction of electrostatically assembled nanoparticles, developed for non-invasive administration of human insulin, with cell membrane mimics. Interactions between the nanoparticles and differently charged surface-supported model membranes were studied in real-time with the quartz crystal microbalance with dissipation monitoring (QCM-D) technique, in some experiments combined with optical reflectometry. Based on the experimental observations, we conclude that structural rearrangements of the nanoparticles occur upon adsorption to negatively charged lipid membranes. The degree of nanoparticle deformation will have important implications for the induced release of the protein drug load. The presented results provide an example of how a surface-based experimental platform can be used for evaluation of nanosized drug carriers.

Keywords

nanoparticle, human insulin, drug delivery, supported lipid bilayer, QCM-D, reflectometry, DLS, zeta potential

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	[1] E. Sackmann, “Supported Membranes: Scientific and Practical Applications,” Science, Vol. 271, 1996, pp. 43-48.
[2]	[2] O. V. Salata, “Applications of Nanoparticles in Biology and Medicine,” Journal of Nanobiotechnology, Vol. 2, 2004, p. 3.
[3]	[3] V. P. Torchilin, “Multifunctional Nanocarriers,” Advanced Drug Delivery Reviews, Vol. 58, 2006, pp. 1532-1555.
[4]	[4] R. Arshady and K. Kono, “Smart Nanoparticles in Nano- medicine,” Kentus Books, London, 2006.
[5]	[5] A. Kunze, P. Sjovall, B. Kasemo and S. Svedhem, “In Situ Preparation and Modification of Supported Lipid Layers by Lipid Transfer from Vesicles Studied by QCM- D and TOF-SIMS,” Journal of the American Chemical Society, Vol. 131, 2009, p. 2450.
[6]	[6] K. Giger, E. R. Lamberson and J. S. Hovis, “Formation of Complex Three-Dimensional Structures in Supported Lipid Bilayers,” Langmuir, Vol.25 , 2009, pp. 71-74.
[7]	[7] M. Tanaka and E. Sackmann, “Polymer-Supported Mem-branes as Models of the Cell Surface, ” Nature, Vol.437 , 2005, pp, 656-663.
[8]	[8] R. P. Richter, J. L. K. Him, B. Tessier, C. Tessier and A. R. Brisson, “On the Kinetics of Adsorption and Two- Dimensional Self-Assembly of Annexin A5 on Supported Lipid Bilayers,” Biophysical Journal, Vol.89, 2005, pp. 3372-3385.
[9]	[9] G. S. Mack, “Pfizer dumps Exubera,” Nature Biotech-nology, Vol.25, 2007, pp. 1331-1332.
[10]	[10] C. Schatz, J.M. Lucas, C. Viton, A. Domard, C. Pichot and T. Delair, “Formation and Properties of Positively Charged Colloids Based on Polyelectrolyte Complexes of Biopolymers,” Langmuir, Vol. 20, 2004, pp. 7766-7778.
[11]	[11] S. M. Hartig, R. R. Greene, M. M. Dikov, A. Prokop and J. M. Davidson, “Multifunctional Nanoparticulate Polye-lectrolyte Complexes,” Pharmaceutical Research, Vol.24 , 2007, pp 2353-2369.
[12]	[12] D. R. Owens, B. Zinman and G. B. Bolli, “Insulins Today and beyond,” Lancet, Vol.358, 2001, pp. 739-746.
[13]	[13] M. Edvardsson, S. Svedhem, G. Wang, R. Richter, M. Rodahl and B. Kasemo, “QCM-D and Reflectometry In-strument: Applications to Supported Lipid Structures and Their Biomolecular Interactions,” Analytical Chemistry, Vol.81, 2009, pp. 349-361.
[14]	[14] M. J. Hope, M. B. Bally, G. Webb and P. R. Cullis, “Pro-duction of Large Unilamellar Vesicles by a Rapid Extru-sion Procedure. Characterization of Size Distribution, Trapped Volume and Ability to Maintain a Membrane Potential,” Biochimica Et Biophysica Acta, Vol. 812, 1985, pp. 55-65.
[15]	[15] A. Kunze, S. Svedhem and B. Kasemo, “Lipid Transfer between Charged Supported Lipid Bilayers and Oppo-sitely Charged Vesicles,” Langmuir, Vol.25, 2009, pp. 5146- 5158.
[16]	[16] R. P. Richter, R. Bérat and A. R. Brisson, “Formation of Solid-Supported Lipid Bilayers: An Integrated View,” Langmuir, Vol. 22, 2006, pp. 3497-3505.
[17]	[17] G. Wang, M. Rodahl, M. Edvardsson, S. Svedhem, G. Ohlsson, F. H??k and B. Kasemo, “A Combined Reflec-tometry and Quartz Crystal Microbalance with Dissipa-tion Setup for Surface Interaction Studies,” Review of Scientific Instruments, Vol. 79, 2008, p. 075107.
[18]	[18] Z. Salamon and G. Tollin, “Optical Anisotropy in Lipid Bilayer Membranes: Coupled Plasmon-Waveguide Reso-nance Measurements of Molecular Orientation, Polariza-bility, and Shape,” Biophysical Journal, Vol. 80, 2001, pp. 1557-1567.
[19]	[19] E. Reimhult, F. Hook and B. Kasemo, “Intact Vesicle Adsorption and Supported Biomembrane Formation From Vesicles in Solution: Influence of Surface Chemistry, Vesicle Size, Temperature, and Osmotic Pressure,” Lang-muir, Vol. 19, 2003, pp. 1681-1691.
[20]	[20] D. Johannsmann, “Viscoelastic, Mechanical, and Dielec-tric Measurements on Complex Samples with the Quartz Crystal Microbalance,” Physical Chemistry Chemical Physics, Vol. 10, 2008, pp. 4516-4534.
[21]	[21] M. V. Voinova, M. Jonson and B. Kasemo, “Missing Mass Effect in Biosensor's QCM Applications,” Biosen-sors & Bioelectronics, Vol. 17, 2002, pp. 835-841.
[22]	[22] R. P. Richter, K. K. Hock, J. Burkhartsmeyer, H. Boehm, P. Bingen, G. L. Wang, N.F. Steinmetz, D.J. Evans and J.P. Spatz, “Membrane-Grafted Hyaluronan Films: A Well-Defined Model System of Glycoconjugate Cell Coats,” Journal of the American Chemical Society, Vol. 129, 2007, p. 5306.
[23]	[23] B. Wang, L. F. Zhang, S. C. Bae and S. Granick, “Nanoparticle-Induced Surface Reconstruction of Phos-pholipid Membranes,” Proceedings of the National Acad-emy of Sciences of the United States of America, Vol. 105, 2008, pp. 18171-18175.
[24]	[24] J. Solon, P. Streicher, R. Richter, F. Brochard-Wyart and P. Bassereau, “Vesicles Surfing on a Lipid Bilayer: Self-Induced Haptotactic Motion,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, 2006, pp. 12382-12387.
[25]	[25] P. R. Leroueil, S. A. Berry, K. Duthie, G. Han, V. M. Rotello, D. Q. McNerny, J. R. Baker, B. G. Orr and M. M. B. Holl, “Wide Varieties of Cationic Nanoparticles In-duce Defects in Supported Lipid Bilayers,” Nano Letters, Vol. 8, 2008, pp. 420-424.
[26]	[26] E. Reimhult, F. Hook and B. Kasemo, “Vesicle Adsorp-tion on SiO2 and TiO2: Dependence on Vesicle Size,” Journal of Chemical Physics, Vol. 117, 2002, pp. 7401- 7404.
[27]	[27] J. Fatisson, R. F. Domingos, K. J. Wilkinson and N. Tufenkji, “Deposition of TiO2 Nanoparticles onto Silica Measured Using a Quartz Crystal Microbalance with Dis-sipation Monitoring,” Langmuir, Vol. 25, 2009, pp. 6062- 6069.
[28]	[28] I. K. Vockenroth, P. P. Atanasova, J. R. Long, A. T. A. Jenkins, W. Knoll and I. Koper, “Functional Incorpora-tion of the Pore Forming Segment of AChR M2 into Tethered Bilayer Lipid Membranes,” Biochimica Et Bio-physica Acta-Biomembranes, Vol. 1768, 2007, pp. 1114- 1120.