Transcript (PPTX)

Light-Guiding Polymer
Drug-Delivery System
Andrew Isherwood, Brian Lawrey,
Phil Szymanski, Eugenia Volkova
Evaluation of Properties: Index of Refraction
● No function to calculate index of refraction for a polymer a
1,2
priori
● •Monomer units with high indices of refraction
o •Carboxymethylated Chitosan ~1.332
3
o •Poly(n-isopropyl acylamide) ~1.552
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
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)
Abbe’s Number
•High value desired (>40)
•No correlative method available for polymer
•Able to estimate by volume fraction
1. Eric Fest. Modeling Scatter in Composite Media.
1
Total Internal reflection
● Total internal reflection (TIR)
o phenomenon when material has high refractive index
o Critical angle 𝜽𝒄 = 𝐚𝐫𝐜𝐬𝐢𝐧 𝒏𝟐 𝒏𝟏
● High water content allows for TIR
𝑑=
𝜆
2𝜋𝑛1 sin2 𝜃 − 𝑛2 𝑛1
2
𝐸𝑧 = 𝐸0 exp − 𝑧 𝑑
poly(N-isopropylacrylamide)
● Thermo-sensitive
● Free Radical
Polymerization
● LCST of 32oC
● Non-biodegradable
● low polymer mass per
unit volume
Chitosan
Crosslinking co-polymer
UV crosslinking
Nanoparticles for drug delivery
● Most drugs limited by poor solubility, high toxicity, high dosage, nonspecific delivery, and in vivo degradation
● Nanotechnology is a solution
o Nanoparticles (NPs) - metal based, magnetic, ceramic, polymeric
 Therapeutics
 Diagnostics
 Imaging
o Sizes range from 10-1000nm in diameter
o Drugs can be loaded by encapsulation, surface attachment, or
entrapment
Parveen, 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.
Nanomaterials
● Nanomaterials are typically divided into two distinct groups- soft and
hard NMs
o 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 research
o Metal toxicity is a huge concern for biomedical application of
nanoparticles
o not as widely researched as soft NMs for medical applications
Toxicity of Nanoparticles
● Selection of a nanoparticle type must focus on a metal that will not
cause metal poisoning
o Zn oxide has been used (sunscreen) and Ti oxide
(pharmaceutical tablets) but may present toxicity issues
o Two nanoparticles types were found that have been used in
biomedical research- iron oxide and gold
Gold Nanoparticles
● Gold nanoparticles have been studied for a wide range of
applications
o Diagnostic useso Therapeutic uses- targeting of tumors with deactivating agents
● Focus will be on a therapeutic use
Photothermal Activation - Au
● Gold-silica nanoshells were used in a hydrogel
o these nanoparticles have a “tunable plasmon resonance”
o resonance is based on shell thickness and core size
● Exposition to wavelengths of light that match the resonance causes
electron band oscillation, which in turn releases heat
o These wavelengths are far above those that the body’s cells can
absorb, so they can pass through biological tissue without incident
● The hydrogel used collapsed at a temp range of 37-45 degrees Celsius
o This range is important, as its proximity to body temperature makes it
an ideal choice for biological uses
● The heat released by the gold nanoparticles causes the hydrogel to
collapse, resulting in a release of the nanoparticles
Gold Nanoparticle Vesicles
● Gold nanoparticles coated with semi-fluorinated ligands self assemble into
vesicles in THF
o Sub-100 nm diameter
● Cross-linked with dithiol-PEG
o More robust
o Showed twice the level of cellular uptake compared to dispersed
AuNPs
● Encapsulated molecules released much more rapidly upon laser irradiation
than upon solvent heating
o Maintain vesicular structure after irradiation
o 532 nm laser
Niikura, 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>.
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 issues
● Maghnetite and Maghemite are the most biocompatible- potentially
nontoxic
Magnetic NPs
● Magnetic fluids - stable colloidal suspensions of magnetic NPs in organic
or inorganic liquid carriers
o Ability to target specific site using locally applied magnetic field
● Two types of iron oxide - magnetite and maghemite
o Both magnetize strongly under external field, but retain no permanent
magnetism
o Magnetite is biocompatible
● Precoating with natural polymers makes them biostable, biodegradable
and nontoxic
● Can be made hollow or solid - hollow have higher drug loading potential
Xing, 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.
Magnetic Nanoparticle Hydro Gel
● MagNaGelTM
● Maghemite Particles
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 boundaries
o EPR - enhanced permeability and retention effect
● High drug-loading capacity
● Controlled release profile for incorporated drug
● Can be made target specific by chemical attachment of targeting
moiety
● Effectively used with diazepam, indomethacin, adriamycin,
anthracycline antibiotics
Final Project Consensus
Material: Poly(N-isopropylacrylamide)
Crosslinker: Chitosan
Means of polymerization: UV-Crosslinking
Nanoparticle: Gold nanoparticles
Drug: ?
Disease:Cancer
Means by which nanoparticle and drug are linked: Encapsulation
Materials
Material
Amount
Cost
Poly(N-isopropylacrylamide) MW 20,000 - 40,000
10g
$240
Chitosan
50g
$50
Optical fiber
1
Borrow
Total
$290
Testing Goals
● Synthesize and crosslink our hydrogel
● Measure the optical properties (Abbe’s number, refractivity) of both
the polymeric materials
● Synthesize and crosslink the nanoparticles
● Test nanoparticle loading
● Develop diffusion model from nanoparticles
● Test various optical fibers over temperature ranges
Required Measurements
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Rainometer: elastic moduli of materials
Refractometer: refractive index, abbe number
Mass measurements: density, degree of swelling
Flourescence detection: light exiting polymer
Thermogravimetric analysis: LCST temperature, particle loading
Differential Scanning Calorimetry: melting temp, heat capacity
Spectrophotometer: particle size
Differential light scattering: particle size