Drug delivery with Hydrogel

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With Hydrogel DRUG DELIVERY

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Quick View Hydrogel & It’s Advantages Loading and Releasing Mechanism Cartilage Drug Delivery Material Development Characterization Discussion Method of Drug Delivery References

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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).

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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.

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Loading and Release Mechanisms in Hydrogels Drugs are loaded into hydrogels via in situ entrapment or post-fabrication equilibrium partitioning. Drugs are modified with a crosslinkable and cleavable linker that can be liberated once the tethers are degraded hydrolytically or enzymatically . In Multiphase Loading method drugs are pre-loaded into microparticles that are subsequently entrapped in hydrogels . Therapeutics-loaded micro particle

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Factors affecting the drug release from Hydrogels

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Delivery of bioactive molecules in Bone and Cartilage tissue Cartilage is a dense and fibrous connective tissue composed of an extracellular matrix (ECM) that contains collagen type II, proteoglycans , and water. Functions of Cartilage : Absorbing impact forces, Transferring load to the underlying bone, and Allowing low-friction movement of the joint. Articular cartilage

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Material Development Carriers should have particular structure to facilitate cellular infiltration and growth of defected bone & cartilage tissue. UHMWPE (Ultra-high molecular weight polyethylene ) Many macrophage and giant cells are surrounding the particle due to intense foreign-body reactions. PVA - H (Poly vinyl alcohol - Hydrogel ) Almost no foreign-body reactions.

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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.

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Freeze -Thawing method It gives a PVA-H with high mechanical strength, high water content, and excellent transparency. Keeping at −20 °C for 10 hrs Agitating under a nitrogen air current Adding Ethanol Vaccum Drying (100 – 120 °C) PVA Drygel PVA + DMSO Solution

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Importance of Hydrogel Infiltration Macroscopic appearance Cross-sectional appearance Histological appearance Microradiograph appearance

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Injection Molding Method PVA DMSO/H 2 O solution (8:2) Melting Injection Molding PVA Hydrogel At 150,160,180,200 °C Injection Pressure 120 MPa Injection Velocity 10 cm³/sec Injection at 150,160,180,200 °C

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Influence of heating temperature on Tensile Strength Degree of polymerization: 8,800 Water content: 30%

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Stress – Strain curves of various PVA - Hydrogel Samples PVA – H water content: 20% PVA – H W.C : 45% PVA – H W.C : 90% Articular Cartilage Meniscus

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

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Frictional Coefficient of Materials In Synovial fluid

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Method of Drug Delivery Mesenchymal stem cells (MSCs) can repair the damaged cartilages. Bioactive factors formed by MSCs have been shown to inhibit tissue scarring, suppress apoptosis, stimulate angiogenesis, and enhance mitosis of tissue-intrinsic stem or progenitor cells. MSCs embedded in a collagen type I hydrogel can be used for tissue engineering of cartilage Matrix-based MSC Magnified view: After 10 days of culture Isolated defected Cartilage Macroscopic Appearance: After treatment

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PVA is non-adhesive to cells and proteins, but can be covalently modified with cell attachment peptides for bioactive regulation. Future Developments Using injectable hollow, biodegradable nanofiber spheres as cell carriers is likely to repair knee cartilage more effectively than current methods. References 1. Masanori Kobayashi and Hyon Suong Hyu . Development and Evaluation of Polyvinyl Alcohol- Hydrogels as an Artificial Atrticular Cartilage Materials 2010, 3, 2753-2771 Ulrich Nöth , Andre F Steinert and Rocky S Tuan . Technology Insight: adult mesenchymal stem cells for osteoarthritis therapy Nature Clinical Practice Rheumatology (2008) 4, 371-380 3. Maha Nasr Sayed Aly Intra- Articular Drug Delivery: A Fast Growing Approach Recent Patents on Drug Delivery & Formulation 2008, 2, 231-237

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