Nanoparticles for Drug Delivery Mark...
Why Care about Particle Size? Tablets - Suspensions Size of active ...
Particle Size and Dissolution XS is the mass of solid drug (mg), t is time (minutes), D is the drug diffusivity (...
Effect of API Particle Size on Content Uniformity = unit dose© 2013 HORIBA, Ltd....
Size Scale© 2013 HORIBA, Ltd. All rights reserved.
Size, Technique, Samples LA-950 SZ-100 ...
Particle Size by DLS: SZ-100 Two sizing angles 90° for size and MW, A2 ...
Laser Diffraction Particle size 0.01 – 3000 µm •Converts scattered lig...
Why Nanoparticles? Greater surface area/volume ratio = more exposed surface = faster dissolution Greater bio-availab...
Making Nanoparticles  Top Down  Bottom Up  Make particles smaller ...
API Processing Elan NanoCrystal® Technology© 2013 HORIBA, Ltd. All rights reserved.
Top Down: Elan NanoMill LA-950 in next room© 2013 HORIBA, Ltd. All ri...
Size Reduction Measured on LA-950© 2013 HORIBA, Ltd. All rights reserved.
API Processing Microfluidizer* * See http://www.microfluidicscorp.com/...
Liposomes 100 nm© 2013 HORIBA, Ltd. All rights reserved.
Liposome: Before, After Microfluidizer© 2013 HORIBA, Ltd. All rights reserved.
Size Reduction Measured on LA-950* Zn-insulin Starting mean size 16.162 µm Milled in sodium deoxycholate and water a...
PLA Nanoparticles for Drug Delivery Targeting ligand provides ...
Nanoparticles for Drug Delivery Good batch ...
PLA Nanoparticle A: DLS & Diffraction DLS on SZ-100 Laser diffraction by LA-950© 2013 HORIBA, ...
PLA Nanoparticle B: DLS & Diffraction DLS on SZ-100 Laser diffraction by LA-950© 2013 HORIBA, ...
Intensity vs. Volume Results Mean by DLS 117 to 95 nm© 2013 HORIBA, Ltd. All rights reserved.
Laser Diffraction vs. DLS Both laser diffraction and DLS Fenofibrate nanosuspensi...
PLA Nanoparticles Laser diffraction or dynamic light scattering? Good batch ...
Colloidal Gold: Drug Delivery* Cancer therapy delivers drug to all rapidly dividing cells Prodrugs delivered in inactiv...
Colloidal Gold: Drug Delivery* Start with 50nm gold particles Incubate with varying molar equivale...
Colloidal Gold: Drug Delivery* Base particle Size 51 nm Zeta potential - 52 mV NfnB ~ 5 nm Combined ~ 60 nm ...
Zeta Potential: Dispersion Stability, IEPMeasures particle surface chargeHigh zeta potential = stable 60 ...
Zeta Potential Cells Gold coated electrodes (ruined) Carbon coated electrodes ...
Zeta Potential: Study Surfaces* FePt-nanoparticle/PDDA/silica composite particles concentrations of PDDA aqueous solutions...
Summary Both DLS and laser diffraction successfully used for size of nanoparticles for...
Resources: www.horiba.com/particle Receive news of updates ...
of 32

Nanoparticles for Drug Delivery Applications

Mark Bumiller from HORIBA Scientific (http://www.horiba.com/particle) discusses how the size and zeta potential of nanoparticles affects performance in drug delivery applications. This talk will be useful for any user of the HORIBA LA-950 or SZ-100 particle size analyzers or any laser diffraction or dynamic light scattering user in general.
Published on: Mar 3, 2016
Published in: Technology      
Source: www.slideshare.net


Transcripts - Nanoparticles for Drug Delivery Applications

  • 1. Nanoparticles for Drug Delivery Mark Bumiller© 2013 HORIBA, Ltd. All rights reserved.
  • 2. Why Care about Particle Size? Tablets - Suspensions Size of active  Same dissolution & ingredient effects content uniformity dissolution & content issues uniformity  Ability to stay in Size influences tablet suspensions hardness  Mouth feel Size and shape effects packing Size and shape effect powder flow© 2013 HORIBA, Ltd. All rights reserved.
  • 3. Particle Size and Dissolution XS is the mass of solid drug (mg), t is time (minutes), D is the drug diffusivity (cm2/min), X0 is the initial drug mass (mg), r is the drug density (mg/mL), h is the diffusion layer thickness (cm), r0 is the initial particle radius (cm), CS is the drug solubility (mg/mL), Xd is the mass of dissolved drug (mg), V is the volume of dissolution media (mL).David R. Friend, PhD; Gregory E. Parry, PhD; T. Francis, PhD; Gary Kupperblatt, PhD; Suggy S. Chrai, PhD; and Gerald Slack,Mathematical Modeling of a Novel Controlled-Release Dosage FormDrug Delivery Technology,•© 2013 HORIBA, Ltd. All rights reserved.
  • 4. Effect of API Particle Size on Content Uniformity = unit dose© 2013 HORIBA, Ltd. All rights reserved.
  • 5. Size Scale© 2013 HORIBA, Ltd. All rights reserved.
  • 6. Size, Technique, Samples LA-950 SZ-100 Proteins Dendrimers Polymeric nanoparticles Liposomes© 2013 HORIBA, Ltd. All rights reserved.
  • 7. Particle Size by DLS: SZ-100 Two sizing angles 90° for size and MW, A2 Backscatter (173°) Particles moving (High conc.) due to Brownian motion Particles Laser PD Attenuator For T% 532nm, 10mW Two cell positions: center and side Zeta potential Attenuator Modulator SZ-100 Optical Diagram© 2013 HORIBA, Ltd. All rights reserved.
  • 8. Laser Diffraction Particle size 0.01 – 3000 µm •Converts scattered light to particle size distribution •Quick, repeatable •Powders and suspensions •Most common technique© 2013 HORIBA, Ltd. All rights reserved.
  • 9. Why Nanoparticles? Greater surface area/volume ratio = more exposed surface = faster dissolution Greater bio-availability, small drug doses and less toxicity Small enough to avoid removal by MPS Large enough to avois rapid renal filtration Can cross cell membranes Interact on cell surface (receptors) Targeting© 2013 HORIBA, Ltd. All rights reserved.
  • 10. Making Nanoparticles  Top Down  Bottom Up  Make particles smaller  Build from atomic or molecular level up Self assembly of micelles© 2013 HORIBA, Ltd. All rights reserved.
  • 11. API Processing Elan NanoCrystal® Technology© 2013 HORIBA, Ltd. All rights reserved.
  • 12. Top Down: Elan NanoMill LA-950 in next room© 2013 HORIBA, Ltd. All rights reserved.
  • 13. Size Reduction Measured on LA-950© 2013 HORIBA, Ltd. All rights reserved.
  • 14. API Processing Microfluidizer* * See http://www.microfluidicscorp.com/© 2013 HORIBA, Ltd. All rights reserved.
  • 15. Liposomes 100 nm© 2013 HORIBA, Ltd. All rights reserved.
  • 16. Liposome: Before, After Microfluidizer© 2013 HORIBA, Ltd. All rights reserved.
  • 17. Size Reduction Measured on LA-950* Zn-insulin Starting mean size 16.162 µm Milled in sodium deoxycholate and water at neutral pH Un-milled Milled *Merisko-Liversidge et. Al., Insulin Nanoparticles: A Novel Formulation Approach for Poorly Water Soluble Zn-Insulin, Pharmaceutical Research, Vol. 21, No. 9, September 2004© 2013 HORIBA, Ltd. All rights reserved.
  • 18. PLA Nanoparticles for Drug Delivery Targeting ligand provides recognition, enabling targeted nanoparticles to identify and bind to their intended target site. Surface functionalization shields targeted nanoparticles from the immune system. Polymer matrix encapsulates payload molecules in a matrix of biodegradable polymers . Therapeutic payloads include small molecules, peptides, proteins, etc. PLA© 2013 HORIBA, Ltd. All rights reserved.
  • 19. Nanoparticles for Drug Delivery Good batch Bad batch 9 fold increase© 2013 HORIBA, Ltd. All rights reserved.
  • 20. PLA Nanoparticle A: DLS & Diffraction DLS on SZ-100 Laser diffraction by LA-950© 2013 HORIBA, Ltd. All rights reserved.
  • 21. PLA Nanoparticle B: DLS & Diffraction DLS on SZ-100 Laser diffraction by LA-950© 2013 HORIBA, Ltd. All rights reserved.
  • 22. Intensity vs. Volume Results Mean by DLS 117 to 95 nm© 2013 HORIBA, Ltd. All rights reserved.
  • 23. Laser Diffraction vs. DLS Both laser diffraction and DLS Fenofibrate nanosuspensions* can measure 30 – 1000 nm Which to use? Sample volume Published data for sample type Beware volume vs. intensity Flavor emulsions ** distributions Also need zeta potential? Then DLS * Anhalt et. al,. Development of a New Method to Assess Nanocrystal Dissolution Based on Light Scattering, Pharm Res (2012) 29:2887–2901 **AN203 DLS vs. Diffraction of Flavor Emulsions© 2013 HORIBA, Ltd. All rights reserved.
  • 24. PLA Nanoparticles Laser diffraction or dynamic light scattering? Good batch Spiked with large particles (DLS) would never see this DLS found second peak,but not >10 µm particles© 2013 HORIBA, Ltd. All rights reserved.
  • 25. Colloidal Gold: Drug Delivery* Cancer therapy delivers drug to all rapidly dividing cells Prodrugs delivered in inactive enzyme form Once delivered, metabolized in D vivo into active metabolite D Study: Immobilize prodrug tumor cell activating enzyme onto colloidal gold particles Enzymes: genetically modified nitroreductase from E. coli;NfnB and Cys-NfnB Colloidal Gold Modified with a Genetically Engineered Nitroreductase: Toward a Novel Enzyme Delivery System for Cancer Prodrug Therapy, Vanessa V. Gwenin, Chris D. Gwenin, and Maher Kalaji Langmuir, 2011, 27 (23), pp 14300–14307© 2013 HORIBA, Ltd. All rights reserved.
  • 26. Colloidal Gold: Drug Delivery* Start with 50nm gold particles Incubate with varying molar equivalents (90:1, 180:1, 270:1,360:1, and 450:1) of purified recombinant Cys-NfnB or His- NfnB overnight at 4C Analyzed on SZ-100 for particle size and zeta potential Colloidal Gold Modified with a Genetically Engineered Nitroreductase: Toward a Novel Enzyme Delivery System for Cancer Prodrug Therapy, Vanessa V. Gwenin, Chris D. Gwenin, and Maher Kalaji Langmuir, 2011, 27 (23), pp 14300–14307© 2013 HORIBA, Ltd. All rights reserved.
  • 27. Colloidal Gold: Drug Delivery* Base particle Size 51 nm Zeta potential - 52 mV NfnB ~ 5 nm Combined ~ 60 nm less ordered more ordered Colloidal Gold Modified with a Genetically Engineered Nitroreductase: Toward a Novel Enzyme Delivery System for Cancer Prodrug Therapy, Vanessa V. Gwenin, Chris D. Gwenin, and Maher Kalaji Langmuir, 2011, 27 (23), pp 14300–14307 © 2013 HORIBA, Ltd. All rights reserved.
  • 28. Zeta Potential: Dispersion Stability, IEPMeasures particle surface chargeHigh zeta potential = stable 60 50Low zeta = unstable, aggregate 40 30 Zeta potenti /m V 20 al 10 0 -102. 0 3. 0 4. 0 5. 0 6. 0 7. 0 8. 0 9. 0 10. 0 -20 -30 -40 -50 -60 pH© 2013 HORIBA, Ltd. All rights reserved.
  • 29. Zeta Potential Cells Gold coated electrodes (ruined) Carbon coated electrodes 20 15 10 zeta potential 5 0 0 2 4 6 8 10 12 14 -5 -10 pH IEP 3.4 nm protein 800 measurements with one cell© 2013 HORIBA, Ltd. All rights reserved.
  • 30. Zeta Potential: Study Surfaces* FePt-nanoparticle/PDDA/silica composite particles concentrations of PDDA aqueous solutions, (A) 1 wt%, (B) 5 wt% and (C) 7 wt% “modification of negatively charged silica template particles with a cationic polymer resulted in the zeta potential of the silica template particles changing from negative to positive. The adsorption of PDDA molecules on the surface of silica particles was confirmed by measuring their zeta potentials.” *Fuchigami et. al., Size-tunable drug-delivery capsules composed of a magnetic nanoshell, Biomatter 2:4, 313–320; October/November/December 2012© 2013 HORIBA, Ltd. All rights reserved.
  • 31. Summary Both DLS and laser diffraction successfully used for size of nanoparticles for drug delivery DLS for smallest sizes, sample volume, concentration Also zeta potential Laser diffraction when also need to detect large particles© 2013 HORIBA, Ltd. All rights reserved.
  • 32. Resources: www.horiba.com/particle Receive news of updates View application notes, webinars, etc.© 2013 HORIBA, Ltd. All rights reserved.

Related Documents