Effect of isotonic solutions and peptide adsorption on zeta potential of porous silicon nanoparticle drug delivery formulations.

Recently, highly promising results considering the use of porous silicon (PSi) nanoparticles as a controlled and targeted drug delivery system have been published. Drugs are typically loaded into PSi nanoparticles by electrostatic interactions, and the drug-loaded nanoparticles are then administered parenterally in isotonic solutions. Zeta potential has an important role in drug adsorption and overall physical stability of nanosuspensions. In the present study, we used zeta potential measurements to study the impact of the formulation components to the nanosuspension stability. The impact of medium was studied by measuring isoelectric points (IEP) and zeta potentials in isotonic media. The role of drug adsorption was demonstrated with gastrointestinal peptides GLP-1(7-37) and PYY (3-36) and the selection of isotonic additive was demonstrated with peptide-loaded PSi nanoparticles. The results show the notable effect of isotonic solutions and peptide adsorption on zeta potential of PSi nanosuspensions. As a rule of thumb, the sugars (sucrose, dextrose and mannitol) seem to be good media for negatively charged peptide-loaded particles and weak acids (citric- and lactic acid) for positively charged particles. Nevertheless, perhaps the most important rule can be given for isotonic salt solutions which all are very poor media when the stability of nanosuspension is considered.

[1]  Sudipta Seal,et al.  Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. , 2007, Biomaterials.

[2]  Victor S-Y Lin,et al.  Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. , 2011, ACS nano.

[3]  A. Lehninger Principles of Biochemistry , 1984 .

[4]  Vesa-Pekka Lehto,et al.  Biocompatibility of thermally hydrocarbonized porous silicon nanoparticles and their biodistribution in rats. , 2010, ACS nano.

[5]  T. Schwartz,et al.  The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR. , 2006, Biochemistry.

[6]  Victor S-Y Lin,et al.  Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. , 2006, Journal of the American Chemical Society.

[7]  V. Lehto,et al.  Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[8]  I. D. Morrison,et al.  Improved techniques for particle size determination by quasi-elastic light scattering , 1985 .

[9]  J. J. Led,et al.  Structure and folding of glucagon‐like peptide‐1‐(7–36)‐amide in aqueous trifluoroethanol studied by NMR spectroscopy , 2001 .

[10]  S. Bloom,et al.  Gut hormones and appetite control. , 2007, Gastroenterology.

[11]  L. Karhunen,et al.  Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans , 2008, Regulatory Peptides.

[12]  Hans-Joachim Wittmann,et al.  Nanofibers resulting from cooperative electrostatic and hydrophobic interactions between peptides and polyelectrolytes of opposite charge. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[13]  A. Sillero,et al.  Derivation and use of a formula to calculate the net charge of acid-base compounds. Its application to amino acids, proteins and nucleotides , 1986 .

[14]  J. Rosenholm,et al.  On the nature of the Brønsted acidic groups on native and functionalized mesoporous siliceous SBA-15 as studied by benzylamine adsorption from solution. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[15]  R. J. Hunter Foundations of Colloid Science , 1987 .

[16]  Dennis E. Koppel,et al.  Analysis of Macromolecular Polydispersity in Intensity Correlation Spectroscopy: The Method of Cumulants , 1972 .

[17]  H. Santos,et al.  ¹⁸F-labeled modified porous silicon particles for investigation of drug delivery carrier distribution in vivo with positron emission tomography. , 2011, Molecular pharmaceutics.

[18]  C. Prestidge,et al.  Thermal oxidation for controlling protein interactions with porous silicon. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[19]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[20]  Nicolas H Voelcker,et al.  The biocompatibility of porous silicon in tissues of the eye. , 2009, Biomaterials.

[21]  Hiroyuki Ohshima,et al.  A Simple Expression for Henry's Function for the Retardation Effect in Electrophoresis of Spherical Colloidal Particles , 1994 .

[22]  J. Lyklema,et al.  Electrophoretic study of polymer adsorption: Dextran, polyethylene oxide and polyvinyl alcohol on silver iodide. , 1988 .

[23]  Nathan Kohler,et al.  Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. , 2002, Biomaterials.

[24]  Zhen Gu,et al.  Tailoring nanocarriers for intracellular protein delivery. , 2011, Chemical Society reviews.

[25]  Charalambos Kaittanis,et al.  Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. , 2010, ACS nano.

[26]  J. Santamaría,et al.  Magnetic nanoparticles for drug delivery , 2007 .

[27]  Jessica M. Rosenholm and,et al.  Wet-Chemical Analysis of Surface Concentration of Accessible Groups on Different Amino-Functionalized Mesoporous SBA-15 Silicas , 2007 .

[28]  M. Vallet‐Regí,et al.  Surface electrochemistry of mesoporous silicas as a key factor in the design of tailored delivery devices. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[29]  Victor S-Y Lin,et al.  Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins. , 2007, Journal of the American Chemical Society.

[30]  Susanne Hostrup,et al.  Recent trends in stabilising peptides and proteins in pharmaceutical formulation – considerations in the choice of excipients , 2009, Expert opinion on drug delivery.

[31]  Phapanin Charoenphol,et al.  Dynamic and cellular interactions of nanoparticles in vascular-targeted drug delivery (review) , 2010, Molecular membrane biology.

[32]  J. Heino,et al.  On the complexity of electrostatic suspension stabilization of functionalized silica nanoparticles for biotargeting and imaging applications , 2008 .

[33]  Alexander T. Florence,et al.  Physicochemical Principles of Pharmacy , 1988 .

[34]  L. Canham Bioactive silicon structure fabrication through nanoetching techniques , 1995 .

[35]  A. Loni,et al.  Sustained antibacterial activity from triclosan-loaded nanostructured mesoporous silicon. , 2010, Molecular pharmaceutics.

[36]  Mauro Ferrari,et al.  The association of silicon microparticles with endothelial cells in drug delivery to the vasculature. , 2009, Biomaterials.

[37]  W. Nelson,et al.  Zeta potential and electroosmotic mobility in microfluidic devices fabricated from hydrophobic polymers: 1. The origins of charge , 2008, Electrophoresis.

[38]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[39]  R. C. Weast CRC Handbook of Chemistry and Physics , 1973 .

[40]  J. Salonen,et al.  Mesoporous silicon in drug delivery applications. , 2008, Journal of pharmaceutical sciences.

[41]  Susan Budavari,et al.  The Merck index , 1998 .

[42]  Mesoporous Silicon (PSi) for Sustained Peptide Delivery: Effect of PSi Microparticle Surface Chemistry on Peptide YY3-36 Release , 2012, Pharmaceutical Research.

[43]  H. Santos,et al.  Drug permeation across intestinal epithelial cells using porous silicon nanoparticles. , 2011, Biomaterials.

[44]  Mauro Ferrari,et al.  Agarose Surface Coating Influences Intracellular Accumulation and Enhances Payload Stability of a Nano-delivery System , 2011, Pharmaceutical Research.

[45]  J. Salonen,et al.  Stabilization of porous silicon surface by thermal decomposition of acetylene , 2004 .

[46]  J. Bacri,et al.  Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. , 2003, Biomaterials.

[47]  D. C. Henry The cataphoresis of suspended particles. Part I.—The equation of cataphoresis , 1931 .

[48]  R. J. Hunter,et al.  Measurement and Interpretation of Electrokinetic Phenomena (IUPAC Technical Report) , 2005 .

[49]  George A. Parks,et al.  The Isoelectric Points of Solid Oxides, Solid Hydroxides, and Aqueous Hydroxo Complex Systems , 1965 .

[50]  Vesa-Pekka Lehto,et al.  In vivo delivery of a peptide, ghrelin antagonist, with mesoporous silicon microparticles. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[51]  Michael J Sailor,et al.  Biodegradable luminescent porous silicon nanoparticles for in vivo applications. , 2009, Nature materials.