With Hydrogel

DRUG DELIVERY

Quick View

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

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…

Thank you…Presented By

chem.adams@gmail.com