Silica-Based PowerPoint Presentation

Silica-Based PowerPoint Presentation

2016-04-24 105K 105 0 0

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Matrixes . for Drug . Delivery:. Ready for a Prime Time?. Dr. Alex . Nivorozhkin. Neo-Advent Technologies LLC, USA. 1. Traditional Uses of Amorphous Silica in Pharma . Non-Porous. Particle. Size. Applications. ID: 291509

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Slide1

Silica-Based

Matrixes for Drug Delivery:Ready for a Prime Time?

Dr. Alex NivorozhkinNeo-Advent Technologies LLC, USA

1

Slide2

Traditional Uses of Amorphous Silica in Pharma

Non-PorousParticle SizeApplicationsFunctionSpherical5-50 micronsTabletsFlow, AnticakingFumed (Branched)0.1-1 micronsGels, SemisolidsViscosity Modifier

PorousParticle SizeApplicationsFunctionSpherical5-50 nmTabletsFiller, Oil/Wax AbsorbingSilicagel5-50 micronsDessicationMoisture Absorbing

Three Different Physical Attributes:-Shape/Size/ Porosity

2

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide3

Fumed Silica – Viscosity Modifier

3

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide4

Key Pathways to Producing the Silica

Silicagel, Precipitated SilicaNa2Si3O7 + H2SO4 → 3 SiO2 + Na2SO4 + H2O (different pH ranges, the product dehydrated )Sol-Gel processSi(OEt)4→ SiO2 (basic or acid hydrolysis)Mesoporous Silica (MSN, Pore Size 2-50 nm)Si(OEt)4→ SiO2 in the presence of templating surfactant

4

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide5

Toxicology of Silica

Plenty in nature (structural material), but not in humansWhen used orally up to 5 g/kg is safeSNP are more toxicToxicity depends on size, charge, shapeRole of increased solubility with decreased size?Lack of good in vitro-in vivo correlations

5

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide6

Solubility of Silica

Amorphous

pH-dependent, increase at pH>9Equilibrium solubility of Nonporous silica -70 ppm vs. Porous -120 ppmSi(OH)4 is excreted with urine at 1.8 mg/day

Crystalline Forms

Soluble thru conversion to Si(OH)4Insoluble at ambient conditions1 ppm at 400 oCVery stable

6

Neo

-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide7

Mesoporous Silica Nanomaterials (MSN)

Key Properties of MSN

Ordered pore structure (2-50 nm)Huge pore surface/volume (1 cm3/g, 1000 m2/g)Commercial Availability MCM-41 (Aldrich $563/25 g)

Preparation of MSN

Liquid Crystalline Templating (“Mobil Process”, 1992) Variations in surfactant, inorganic framework, conditions

7

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide8

SNP Surface Reactivity

Covalent Attachment Options

Negative Zeta-potential for unmodified SNPProtonated amino groups after modification with 3-aminopropyl triethoxysilane

Drug-SNP Conjugates

Convenient general chemistryCan it match potential for Polymer-Drug conjugates?Can it be produced economically: concentration limits, washout steps, density of conjugation?

8

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide9

Surface Functionalization

Co-condensation (one-pot)

Versatile post-process methodPossible pore clogging

Grafting Method

More homogeneous Distribution

Maybe difficult to fit into the prep

9

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide10

Drug Delivery Modalities

10

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide11

MSN-based Drug Delivery Vehicle

Challenges

Hydrophilic surface (-Si-OH), low loading of hydrophobic drugs (many cancer, CNS leads) ca. 1%Hydrophobic surface modification results in sluggish and incomplete releaseFilling the pores with surfactant improves loading and release

Pore-loading with Capping

11

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide12

MSN as Multifunctional Nanoplatform

Functionalization Domains:

Silica framework Mesopores Outermost surface of nanoparticlesCombination approach

12

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide13

MSN Nanomotor for DNA Capture

M.

Vallet-Regi, Small, 2012

13

Neo

-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide14

What the Future Holds?

Potential

Possibly low toxicMay be cheap Versatile and compatible with various chemistriesCould be commercially as successful as liposomes?New Development ProductsPoorly soluble potent drugs (complement to non-MSN)ImagingTargeted deliveryDelivery of biologics (little explored)Stimuli-triggered delivery

Challenges

Toxicity, particularly long-termManufacturingLow drug loads“Smart” approaches bring add-on issues, may be all of the aboveDriving ForcesSolid industrial baseAdvances in silica applications other than pharma, i.e. catalysis, ink, polymersNeed for new drug delivery technologies

14

Neo-Advent Technologies, LLC, Littleton, MA 01460;

www.neo-adventtec.com

Slide15

Thank

You

Alex Nivorozhkin, Ph.D.Founder, COONeo-Advent Technologies LLC, 410 Great Road, Littleton, MA 1-508-970-4858www.neo-adventtec.comCo-ChairFormulation Drug DeliveryCommittee, Massachusetts Biotechnology Council, Boston

AcknowledgementsMr. Nelson LandrauDr. Ken AveryUnilever, Port Sunlight, UKDr. Craig JonesDr. James MerringtonDr. David Mealing

15

Neo-Advent Technologies, LLC, Littleton, MA 01460; www.neo-adventtec.com

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