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Polymer Nanocapsules. CE 435: Polymer Science & Engineering Emmanuel Lollis Andrew Hyun In Zachary Fine Jin woo Nam Shawreen Manish Shah. List of Contents. Objective Introduction Research Plan General Plan Potential Mechanisms to Trigger Drug Release

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polymer nanocapsules

Polymer Nanocapsules

CE 435: Polymer Science & Engineering

Emmanuel Lollis

Andrew Hyun In

Zachary Fine

Jinwoo Nam

ShawreenManish Shah

list of contents
List of Contents
  • Objective
  • Introduction
  • Research Plan
    • General Plan
    • Potential Mechanisms to Trigger Drug Release
    • Synthesis of Polymer Nanocapsule
    • Verification of Success
  • Broader Impacts
slide3

1

Objective

purpose
Purpose

State-of-the-art Nanocapsule Medications

  • Deliver drugs to specific locations within the body
  • Cuts down on the amount of drug per dose
  • Reduces the risk of side effects

Limitation

  • Designed to target pre-determined areas
objective
Objective

Our end-goal is to overcome this limitation through the design and synthesis of a novel polymer nanocapsule with a target-specific release mechanism that can be changed on-demand.

slide6

2

Introduction

what are nanocapsules
What are Nanocapsules?

Solid Colloidal particles size ranging 100-500nm

Characterized by a core-shell structure formed by self assembling of amphiphilic copolymers

encapsulated drug
Encapsulated Drug
  • Doxorubicin (DOX) is a widely used cancer drug in chemotherapy
  • Has many draw backs
      • Low selectivity
      • High toxicity
      • Poor water-solubility
      • Short half-life
  • Focus is to encapsulate DOX in order to improve drug delivery
slide9

3

Potential Mechanisms to Trigger Drug Release

slide10

Methods of Drug Transport

Hydration & Diffusion

Enzymatic Reaction

Near-Infrared Light

Use of Magnetic Fields

slide11

Enzymatic Reaction

  • Enzymes are secreted by only certain parts of the human body
  • i.e. Stomach = target
    • Coat with polypeptides
    • Pepsin dissolves into amino acids
  • Small intestines: lipase
  • Hundreds of other enzymes
slide12

Near-Infrared Light

Photolysis

Coat nanocapsule with 1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindodicarbocyanine-5,5' (DiD)

Use pulse of photon (~1 ms)

Negative effect: uncaging process during photolysis creates radicals (harmful to cells)

Scavengers are added to remove radicals

slide13

Magnetic Fields

External radio frequency stimulus

Coat with silica

Possible to control release

Efficiency is high

slide14

4

Synthesis of Polymer Nanocapsule

different methods employed
Different methods employed

Anionic polymerization in mini emulsion

Interfacial polymerization

Processing of preformed polymers

Nanoprecipitation

Diffusion emulsification

Double emulsification

material chosen poly butyl cyanoacrylate
Material chosen: Poly (butyl cyanoacrylate)

Has been successful tested as a carrier for other drugs like thymopentin

Easy to synthesize

Sensitive to certain disturbances, to make a timely drug release

When compared on ‘entrapment efficiency’ with other polymeric materials.

preparation of monomer butyl cyanoacrylate
Preparation of Monomer butyl cyanoacrylate

It is synthesized from butyl cyanoacetate

It is used as an adhesive in various applications

Suitable inhibitor are added to prevent It from polymerization.

polymerization of poly butyl cyanoacrylate
Polymerization of poly (butyl cyanoacrylate)

Method to be employed is miniemulsion polymerization.

Mechanism followed is of anionic polymerization

Allows fine tuning of properties of nanocapsules.

Low energy requiring project; no high stirring, high pressure etc.

slide19

Miniemulsion means droplet size of 20-500nm.

This is obtained by either varying the temperature, which is called phase inversion temperature method or the composition, which is called the phase inversion composition method, while keeping the other parameter constant.

The latter one is used here.

Inhibitor like Methanesulfonic acid is added for carrying out uninterrupted emulsification.

Organic and Aqueous phases are reacted by slow addition of aqueous phase.

slide20

Polymerization reaction takes place by initiation by KOH

The drug is loaded in the polymer during the reaction.

Ultracentrifugation is carried out

Nanoparticles thus formed are suspended in a solution for dispersion.

Size of nanoparticles depends upon concentration of surfactants and stabilizers. It is expected to be around 20-100nm.

slide21

Processing preformed polymer

Also known as solvent displacement or interfacial deposition method.

Process contains two phases : Solvent (organic) phase and non-solvent (aqueous) phase.

Polymer is in the solvent phase.

Suitable stabilizer is used e.g. Polysorbate.

slide22

Non Solvent phase is gently added to the solvent phase

Drug is added during the addition.

Process takes place in acidic environment. The system is neutralized after the process.

Nanoparticle formation consists of three stages : Nucleation, growth and aggregation.

Attaining super saturation is the driving force for the system.

characterization of particles
CHARACTERIZATION OF PARTICLES

Particle size and distribution is the most important factor in determining the success of the process.

It establishes several important factors like biocompatibility and target drug delivering capacity.

The time of release is also a function of the particle size.

Surface area is another important factor.

slide24

5

Verification of Success

slide25
Plan

Two sub-phases

  • Phase one
    • infusing the polymer nanocapsules with dye, and then performing tests in liquid solutions
  • Phase two
    • infusing the polymer nanocapsules with the drug Doxorubicin, and then performing tests with living cells
phase one
Phase one

Test 1 – Determine whether or not the nanocapsule can retain its contents over time

Samples

  • Blank (empty nanocapsules)
  • Dye-loaded nanocapsule

Equipment

  • Spectrophotometer

Observing

  • Difference in absorption over time

Desired outcome

  • No difference between the samples over time
phase one1
Phase one

Test 2 – Determine whether or not the nanocapsule can release its contents when triggered

Samples

  • Blank (empty nanocapsules)
  • Dye-loaded nanocapsule

Equipment

  • Spectrophotometer

Observing

  • Difference in absorption after the trigger time

Desired outcome

  • A sharp, immediate difference.
phase one2
Phase one

Test 3 – Determine whether or not the nanocapsule can resist shear forces

Samples

  • Blank (empty nanocapsules)
  • Dye-loaded nanocapsule

Equipment

  • Spectrophotometer
  • Peristaltic pump with tubing

Observing

  • Difference in absorption over time

Desired outcome

  • No difference between the samples over time
phase two
Phase two

Test 1 – Determine whether or not the nanocapsules are toxic to cells

Samples

  • HL-1 cells (control)
  • HL-1 cells (empty nanocapsules)

Equipment

  • Cytotoxicity detection kit
phase two1
Phase two

Test 2 – Conduct a live test on cells

Samples

  • HL-1 cells (control)
  • HL-1 cells (cells exposed to Doxorubicin)
  • HL-1 cells (nanocapsules loaded with Doxorubicin)

Equipment

  • Spectrophotometer
  • RNA Isolation kit
  • RNA to cDNA kit
  • qPCR machine

Observing

  • Gene expression between samples

Desired outcome

  • Similar results with respect to time since drug administration between samples 2 and 3.
slide31

6

Broader Impacts

slide32

Long-Term Potential Influence

Scientific Field

Novel therapeutic systems : hormones, vitamins, antifungals, etc.

Encapsulation : polymers, enzymes, biological cells

Society

Market exceed $30 billion by 2015

Enhance cure rate of cancer

slide33

The Way to Realization the Influence

Combining Two Methods : IR light & DiD(enzyme)

  • IR light -> Control the Time
  • DiD(enzyme) -> Control the Place
  • 1. Have an effect on time.

2. Affect without disturbing neighbor tissues

or organs.