Post on 26-May-2015
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With Hydrogel
DRUG DELIVERY
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Hydrogel & It’s Advantages
Loading and Releasing Mechanism
Cartilage Drug Delivery
Material Development
Characterization Discussion
Method of Drug Delivery
References
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
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
Factors affecting the drug release from Hydrogels
Delivery of bioactive molecules in Bone and Cartilage tissue
Cartilage is a dense and fibrous connective tissuecomposed 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.
Articularcartilage
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.
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
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
AddingEthanol
Vaccum Drying (100 – 120 °C)
PVADrygel
PVA + DMSO Solution
Importance of Hydrogel Infiltration
Macroscopic appearance Cross-sectional appearance Histological appearance Microradiograph appearance
Injection Molding Method
PVA
DMSO/H2O solution
(8:2)
Melting Injection Molding
PVAHydrogel
At 150,160,180,200 °C
Injection Pressure 120 MPaInjection Velocity 10 cm³/sec
Injection at 150,160,180,200 °C
Influence of heating temperature on Tensile Strength
Degree of polymerization: 8,800Water content: 30%
Stress – Strain curves of variousPVA - Hydrogel Samples
PVA – H water content: 20%
PVA – H W.C : 45%
PVA – H W.C : 90%
Articular Cartilage
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
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
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, 2753-27712. Ulrich Nöth, Andre F Steinert and Rocky S Tuan . Technology Insight: adult mesenchymal stem cells for
osteoarthritis therapy Nature Clinical Practice Rheumatology (2008) 4, 371-3803. 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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