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DRUG DELIVERY
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Hydrogel : Swellable Polymeric Materials

     Hydrogels are three dimensional networks of
                hydrophilic polymers.

Extremely absorbent and possess a degree of flexibility
            very similar to natural tissue .

Drug encapsulated in a hydrogel matrix is only released
 after contact with organ-or tumor-specific molecules
                (e.g. surface proteins).
Advantages Of Hydrogels

Adaptable targeting system, allowing great
flexibility for many different drugs.
Offers more accurate drug placement.
Creating a more precise response and fewer
side effects.
Non-toxic and biocompatible, raising the level
of bio-safety for the patient.
Absence of Phagocytosis by macrophages.
Loading and Release Mechanisms in Hydrogels
            In Multiphase Loading method
 Drugs are modified with a microparticles that are
   drugs are pre-loaded into
         subsequently entrapped in hydrogels. into
      crosslinkable and
                             Drugs are loaded
                              hydrogels via in situ
cleavable linker that can be
                              entrapment or post-
 liberated once the tethers
                             fabrication equilibrium
are degraded hydrolytically
                                   partitioning.
              or
        enzymatically.


                                         Therapeutics-loaded micro particle
Factors affecting the drug release from Hydrogels
Delivery of bioactive molecules in Bone and
                     Cartilage tissue




             Articular
             cartilage




   Cartilage is aCartilage : Absorbing impact forces,
   Functions of dense and fibrous connective tissue
composed of an extracellular matrix bone, and Allowing
 Transferring load to the underlying (ECM) that contains
      collagen type II,movement of the joint.
           low-friction proteoglycans, and water.
Material Development
                      UHMWPE
                        PVA - H
     (Ultra-high molecular weight polyethylene )
            (Poly vinyl alcohol - Hydrogel)



 Carriers should have particular structure to facilitate
      cellular infiltration and growth of defected
                bone & cartilage tissue.


Many macrophage and giant cells are surrounding the
   particle due tono foreign-body reactions.
          Almost intense foreign-body reactions.
Poly(Vinyl Alcohol) - Hydrogel




Poly(vinyl alcohol) (PVA) gels have been formed through
        Chemical Crosslinking with aldehydes or
 photopolymerization. It can create harsh environments
             that are potentially toxic to cells.
Freeze -Thawing method

               Agitating under    Keeping at
PVA + DMSO
                a nitrogen air      −20 °C
 Solution
                   current         for 10 hrs


 Adding                    Vaccum Drying         PVA
 Ethanol                    (100 – 120 °C)      Drygel


 It gives a PVA-H with high mechanical strength, high
       water content, and excellent transparency.
Importance of Hydrogel Infiltration




Macroscopic appearance       Microradiograph appearance
                                Histological appearance
                             Cross-sectional
Injection Molding Method


  PVA        At 150,160,180,200 °C


                  Melting                   Injection
                                             Molding
DMSO/H2O
                                      Injection Pressure 120 MPa
 solution                            Injection Velocity 10 cm³/sec
   (8:2)                             Injection at 150,160,180,200 °C




                                              PVA
                                            Hydrogel
Influence of heating temperature on
          Tensile Strength

                    Degree of polymerization: 8,800
                    Water content: 30%
Stress – Strain curves of various
    PVA - Hydrogel Samples
                 PVA – H
             water content: 20%


                   Articular Cartilage
                     PVA – H
                     W.C : 45%

                        PVA – H
                        W.C : 90%

                         Meniscus
Frictional Coefficient of Materials
                     In Synovial fluid




Synovial fluid (simulated lubricants) : Saline with 0.375%
    hyaluronic acid, 3.0% albumin, 0.5% γ-globulin.
Frictional Coefficient of Materials
         In Synovial fluid
Method of Drug Delivery

                                               Magnified view:
Matrix-based MSC                               After 10 days of
                                                     culture




 Isolated defected                               Macroscopic
    Cartilage                                    Appearance:
                                                After treatment


Bioactive factors formed by MSCs have been shown to
MSCs embedded in a collagen type I hydrogel can be
 inhibit tissue scarring, suppress apoptosis, stimulate
         used for tissue engineering(MSCs) can
            Mesenchymal stem cells of cartilage
 angiogenesis, and the damaged cartilages.
              repair enhance mitosis of tissue-intrinsic
                 stem or progenitor cells.
Future Developments
   References
   Using injectable hollow, biodegradable nanofiber
spheres as cell carriers is likely to Suong Hyu.
         1. Masanori Kobayashi and Hyon repair knee cartilage
       more effectively Evaluation of Polyvinyl Alcohol-
            Development and than current methods.
            Hydrogels as an Artificial Atrticular Cartilage
              Materials 2010, 3, 2753-2771
          2. Ulrich Nöth, Andre F Steinert and Rocky S Tuan .
PVA   is non-adhesive to cells and proteins, but for be
              Technology Insight: adult mesenchymal stem cells can
        covalently modified with cell attachment
             osteoarthritis therapy
              Nature Clinical Practice Rheumatology (2008) 4, 371-380
          3. peptidesSayedbioactive regulation.
              Maha Nasr for Aly
              Intra-Articular Drug Delivery: A Fast Growing Approach
             Recent Patents on Drug Delivery & Formulation 2008, 2, 231-237
Thank you…            Thank you…

      Thank you…
      Thank you…

      Thank you…
Thank you… By
        Presented
                  Thank you…
       chem.adams@gmail.com

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Drug delivery with Hydrogel

  • 3. Hydrogel : Swellable Polymeric Materials Hydrogels are three dimensional networks of hydrophilic polymers. Extremely absorbent and possess a degree of flexibility very similar to natural tissue . Drug encapsulated in a hydrogel matrix is only released after contact with organ-or tumor-specific molecules (e.g. surface proteins).
  • 4. Advantages Of Hydrogels Adaptable targeting system, allowing great flexibility for many different drugs. Offers more accurate drug placement. Creating a more precise response and fewer side effects. Non-toxic and biocompatible, raising the level of bio-safety for the patient. Absence of Phagocytosis by macrophages.
  • 5. Loading and Release Mechanisms in Hydrogels In Multiphase Loading method Drugs are modified with a microparticles that are drugs are pre-loaded into subsequently entrapped in hydrogels. into crosslinkable and Drugs are loaded hydrogels via in situ cleavable linker that can be entrapment or post- liberated once the tethers fabrication equilibrium are degraded hydrolytically partitioning. or enzymatically. Therapeutics-loaded micro particle
  • 6. Factors affecting the drug release from Hydrogels
  • 7. Delivery of bioactive molecules in Bone and Cartilage tissue Articular cartilage Cartilage is aCartilage : Absorbing impact forces, Functions of dense and fibrous connective tissue composed of an extracellular matrix bone, and Allowing Transferring load to the underlying (ECM) that contains collagen type II,movement of the joint. low-friction proteoglycans, and water.
  • 8. Material Development UHMWPE PVA - H (Ultra-high molecular weight polyethylene ) (Poly vinyl alcohol - Hydrogel) Carriers should have particular structure to facilitate cellular infiltration and growth of defected bone & cartilage tissue. Many macrophage and giant cells are surrounding the particle due tono foreign-body reactions. Almost intense foreign-body reactions.
  • 9. Poly(Vinyl Alcohol) - Hydrogel Poly(vinyl alcohol) (PVA) gels have been formed through Chemical Crosslinking with aldehydes or photopolymerization. It can create harsh environments that are potentially toxic to cells.
  • 10. Freeze -Thawing method Agitating under Keeping at PVA + DMSO a nitrogen air −20 °C Solution current for 10 hrs Adding Vaccum Drying PVA Ethanol (100 – 120 °C) Drygel It gives a PVA-H with high mechanical strength, high water content, and excellent transparency.
  • 11. Importance of Hydrogel Infiltration Macroscopic appearance Microradiograph appearance Histological appearance Cross-sectional
  • 12. Injection Molding Method PVA At 150,160,180,200 °C Melting Injection Molding DMSO/H2O Injection Pressure 120 MPa solution Injection Velocity 10 cm³/sec (8:2) Injection at 150,160,180,200 °C PVA Hydrogel
  • 13. Influence of heating temperature on Tensile Strength Degree of polymerization: 8,800 Water content: 30%
  • 14. Stress – Strain curves of various PVA - Hydrogel Samples PVA – H water content: 20% Articular Cartilage PVA – H W.C : 45% PVA – H W.C : 90% Meniscus
  • 15. Frictional Coefficient of Materials In Synovial fluid Synovial fluid (simulated lubricants) : Saline with 0.375% hyaluronic acid, 3.0% albumin, 0.5% γ-globulin.
  • 16. Frictional Coefficient of Materials In Synovial fluid
  • 17. Method of Drug Delivery Magnified view: Matrix-based MSC After 10 days of culture Isolated defected Macroscopic Cartilage Appearance: After treatment Bioactive factors formed by MSCs have been shown to MSCs embedded in a collagen type I hydrogel can be inhibit tissue scarring, suppress apoptosis, stimulate used for tissue engineering(MSCs) can Mesenchymal stem cells of cartilage angiogenesis, and the damaged cartilages. repair enhance mitosis of tissue-intrinsic stem or progenitor cells.
  • 18. Future Developments References Using injectable hollow, biodegradable nanofiber spheres as cell carriers is likely to Suong Hyu. 1. Masanori Kobayashi and Hyon repair knee cartilage more effectively Evaluation of Polyvinyl Alcohol- Development and than current methods. Hydrogels as an Artificial Atrticular Cartilage Materials 2010, 3, 2753-2771 2. Ulrich Nöth, Andre F Steinert and Rocky S Tuan . PVA is non-adhesive to cells and proteins, but for be Technology Insight: adult mesenchymal stem cells can covalently modified with cell attachment osteoarthritis therapy Nature Clinical Practice Rheumatology (2008) 4, 371-380 3. peptidesSayedbioactive regulation. Maha Nasr for Aly Intra-Articular Drug Delivery: A Fast Growing Approach Recent Patents on Drug Delivery & Formulation 2008, 2, 231-237
  • 19. Thank you… Thank you… Thank you… Thank you… Thank you… Thank you… By Presented Thank you… chem.adams@gmail.com