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Polymer Nanocapsules

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

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  1. Polymer Nanocapsules CE 435: Polymer Science & Engineering Emmanuel Lollis Andrew Hyun In Zachary Fine Jinwoo Nam ShawreenManish Shah

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

  3. 1 Objective

  4. 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

  5. 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.

  6. 2 Introduction

  7. What are Nanocapsules? Solid Colloidal particles size ranging 100-500nm Characterized by a core-shell structure formed by self assembling of amphiphilic copolymers

  8. 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

  9. 3 Potential Mechanisms to Trigger Drug Release

  10. Methods of Drug Transport Hydration & Diffusion Enzymatic Reaction Near-Infrared Light Use of Magnetic Fields

  11. 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

  12. 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

  13. Magnetic Fields External radio frequency stimulus Coat with silica Possible to control release Efficiency is high

  14. 4 Synthesis of Polymer Nanocapsule

  15. Different methods employed Anionic polymerization in mini emulsion Interfacial polymerization Processing of preformed polymers Nanoprecipitation Diffusion emulsification Double emulsification

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 5 Verification of Success

  25. 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

  26. 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

  27. 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.

  28. 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

  29. 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

  30. 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.

  31. 6 Broader Impacts

  32. 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

  33. 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.

  34. Questions?

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