Light-Guiding Polymer Drug-Delivery System - PowerPoint Presentation

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Light-Guiding Polymer Drug-Delivery System

Andrew Isherwood, Brian Lawrey,

Phil Szymanski, Eugenia Volkova

Slide2

Evaluation of Properties: Index of

Refraction

No function to calculate index of refraction for a polymer

a priori1,2•Monomer units with high indices of refraction•Carboxymethylated Chitosan ~1.332•Poly(n-isopropyl acylamide) ~1.5523

1.

Alan R. Katritzky. "ChemInform Abstract: Correlation and Prediction of the Refractive Indices of Polymers by QSPR."

ChemInform

2.

R.K. Shukla "Density, Refractive Index and Molar Refractivity of Binary Liquid Mixture at 293.15, 298.15, 303.15, 308.15 and 313.15K."

Arabian Journal of Chemistry

3.

M. Reufer "Temperature-sensitive Poly(N-Isopropyl-Acrylamide) Microgel Particles: A Light Scattering Study."

The European Physical Journal E

Slide3

Evaluation of optical properties:

Water

•

Approximation from volume fractions1•Water: n=1.333 System: n~1.34•The system loses transparency at low swelling2•Lower Critical Solution Temperature

1.

M. Reufer "Temperature-sensitive Poly(N-Isopropyl-Acrylamide) Microgel Particles: A Light Scattering Study."

The European Physical Journal E

2.Li-Ming Yang. "Preparation and Characterization of N-isopropylacrylamide/carboxymethylated Chitosan Hydrogel." Journal of Shanghai University (English Edition)

Slide4

Abbe’s Number

•

High value desired (>40)

•No correlative method available for polymer•Able to estimate by volume fraction11. Eric Fest. Modeling Scatter in Composite Media.

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Total Internal reflection

Total internal reflection (TIR)

phenomenon when material has high refractive index

Critical angle High water content allows for TIR

 

 

 

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poly(N-isopropylacrylamide)

Thermo-sensitive

Free Radical Polymerization

LCST of 32oCNon-biodegradablelow polymer mass per unit volume

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Chitosan

Crosslinking co-polymer

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Slide9

UV crosslinking

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Nanoparticles for drug delivery

Most drugs limited by poor solubility, high toxicity, high dosage, non-specific delivery, and in vivo degradation

Nanotechnology is a solution

Nanoparticles (NPs) - metal based, magnetic, ceramic, polymericTherapeuticsDiagnosticsImagingSizes range from 10-1000nm in diameterDrugs can be loaded by encapsulation, surface attachment, or entrapmentParveen, MS, Suphiya, Ranjita Misra, MS, and Sanjeeb K. Sahoo, PhD. "Nanoparticles: A Boon to Drug Delivery, Therapeutics, Diagnostics and Imaging." Nanomedicine: Nanotechnology, Biology and Medicine

(2012): 147–166. Web. 3 Dec. 2014.

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Nanomaterials

Nanomaterials are typically divided into two distinct groups- soft and hard NMs

Soft NMs are polymer and lipid based- many soft systems have gone into clinical trials in a wide variety of medical research topics

Hard NMs include a wide range of metal and metal oxide nanoparticles, which come with their own drawbacks for medical researchMetal toxicity is a huge concern for biomedical application of nanoparticlesnot as widely researched as soft NMs for medical applications

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Toxicity of Nanoparticles

Selection of a nanoparticle type must focus on a metal that will not cause metal poisoning

Zn oxide has been used (sunscreen) and Ti oxide (pharmaceutical tablets) but may present toxicity issues

Two nanoparticles types were found that have been used in biomedical research- iron oxide and gold

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Gold Nanoparticles

Gold nanoparticles have been studied for a wide range of applications

Diagnostic uses-

Therapeutic uses- targeting of tumors with deactivating agentsFocus will be on a therapeutic use

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Photothermal Activation - Au

Gold-silica nanoshells were used in a hydrogel

these nanoparticles have a “tunable plasmon resonance”

resonance is based on shell thickness and core sizeExposition to wavelengths of light that match the resonance causes electron band oscillation, which in turn releases heatThese wavelengths are far above those that the body’s cells can absorb, so they can pass through biological tissue without incidentThe hydrogel used collapsed at a temp range of 37-45 degrees CelsiusThis range is important, as its proximity to body temperature makes it an ideal choice for biological usesThe heat released by the gold nanoparticles causes the hydrogel to collapse, resulting in a release of the nanoparticles

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Gold Nanoparticle Vesicles

Gold nanoparticles coated with semi-fluorinated ligands self assemble into vesicles in THF

Sub-100 nm diameter

Cross-linked with dithiol-PEGMore robustShowed twice the level of cellular uptake compared to dispersed AuNPsEncapsulated molecules released much more rapidly upon laser irradiation than upon solvent heatingMaintain vesicular structure after irradiation 532 nm laserNiikura, Kenichi, Naoki Iyo, Yasutaka Matsuo, Hideyuki Mitomo, and Kuniharu Ijiro. "Sub-100 Nm Gold Nanoparticle Vesicles as a Drug Delivery Carrier Enabling Rapid Drug Release upon Light Irradiation." ACS Applied Materials & Interfaces

(2013): 3900-907. Web. 15 Dec. 2014. <www.acsami.org>.

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Iron Oxide

he

highly paramagnetic nature of iron oxide nanoparticles offers some very useful possibilities for targeted drug delivery

Co and Ni have similar magnetic properties, but iron oxides do not present the same toxicity issuesMaghnetite and Maghemite are the most biocompatible- potentially nontoxic

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Magnetic NPs

Magnetic fluids - stable colloidal suspensions of magnetic NPs in organic or inorganic liquid carriers

Ability to target specific site using locally applied magnetic field

Two types of iron oxide - magnetite and maghemiteBoth magnetize strongly under external field, but retain no permanent magnetismMagnetite is biocompatiblePrecoating with natural polymers makes them biostable, biodegradable and nontoxicCan be made hollow or solid - hollow have higher drug loading potentialXing, Ruijun, Ashwinkumar A. Bhirde, Shouju Wang, Xiaolian Sun, Gang Liu, Yanglong Hou, and Xiaoyuan Chen. "Hollow Iron Oxide Nanoparticles as Multidrug Resistant Drug Delivery and Imaging Vehicles." Nano Research (2013): 1-9. Web. 3 Dec. 2014.

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Magnetic Nanoparticle Hydro Gel

MagNaGel

TM

Maghemite Particles

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Polymeric Micelles

Block copolymers consisting of hydrophilic and hydrophobic monomer units

Increase water solubility of poorly soluble drugs

Improve drug bioavailability by enhancing permeability across physiological boundariesEPR - enhanced permeability and retention effectHigh drug-loading capacityControlled release profile for incorporated drugCan be made target specific by chemical attachment of targeting moietyEffectively used with diazepam, indomethacin, adriamycin, anthracycline antibiotics

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Final Project Consensus

Material:

Poly(

N-isopropylacrylamide)Crosslinker: ChitosanMeans of polymerization: UV-CrosslinkingNanoparticle: Gold nanoparticlesDrug: ?Disease:CancerMeans by which nanoparticle and drug are linked: Encapsulation

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Materials

Material

Amount

Cost

Poly(

N

-isopropylacrylamide) MW 20,000 - 40,000

10g

$240

Chitosan

50g

$50

Optical fiber

1

Borrow

Total

$290

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Testing Goals

Synthesize and crosslink our hydrogel

Measure the optical properties (Abbe’s number, refractivity) of both the polymeric materials

Synthesize and crosslink the nanoparticlesTest nanoparticle loading Develop diffusion model from nanoparticlesTest various optical fibers over temperature ranges

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Required Measurements

Rainometer: elastic moduli of materials

Refractometer: refractive

index, abbe numberMass measurements: density, degree of swellingFlourescence detection: light exiting polymerThermogravimetric analysis: LCST temperature, particle loadingDifferential Scanning Calorimetry: melting temp, heat capacitySpectrophotometer: particle sizeDifferential light scattering: particle size