pH Sensitive Hydrogels In Controlled Release Systems

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pH Sensitive HydrogelsIn Controlled Release
Systems

• By Karin Stephenson
• In partial fulfillment of Chem. 765
• Advanced Polymers

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Contents

• Definition of Hydrogels
• Physical Properties of Hydrogels
• Pore Size Characterization using PAS
• Swelling Mechanisms pH Sensitive Hydrogels
• Introduction of Controlled Release Systems
• Applications of Hydrogels in Controlled Release
  Systems
• PEG Hydrogels in Drug Delivery
• pH Sensitive Hydrogels based on Chitosan and
  D,L-Lactic Acid

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Definition of a Hydrogel

• Hydrogels are three dimensional networks of
  hydrophilic polymers that are insoluble.

Xin, Qu. et al. Synthesis and Characterization
of pH sensitive Hydrogels Based on Chitosan and
D,L-Lactic Acid Journal of Applied Polymer
Science, v.74 3193-3202 (1999)
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Applications of Hydrogels

• Controlled Drug Release
• Wound coverings
• vVigilonTM is a hydrogel used in sheet covering
  wound materials. It is prepared from radiation
  crosslinking of high molecular weight poly
  (ethylene oxide) chains.
• vHypol TM is used in foam wound healing materials
  and in drug delivery. It is a crosslinked PEG
  foam.
• Contact lenses
• Adsorption
• Chromatographic packing material

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Properties of Hydrogels

• Amorphous polymers
• Tg values vary depending on the extent of
  crosslinking.
• Swelling is a result of a change in the external
  environment.
• Hydrogels can swell as a result of changes in pH,
  temperature, ionic strength, solvent composition,
  pressure and the application of electric fields.

N,N-methyl bisacrylamide crosslinker (not
hydrolytically stable)
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Determination of Pore Sizes

• Pore sizes are important to controlled drug
  delivery.
• Current methods include
• Gas diffusion, electron paramagnetic resonance
  (EPR), and fluorescence
• Positron Annihilation Spectroscopy (PAS)
• Allows for the determination of electron density,
  sizes and an indication of the number of pores
  within the polymer.

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pH Sensitive Hydrogels

• Crosslinking is based on hydrogen bonding, and
  secondary hydrophobic interactions.
• Crosslinking is reversible
• Control over the pore sizes

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Controlled Release Systems

• Release characteristics are dependent on the
  chemical nature of the hydrogel
• Hydrogel Requirements
• Controlled or delayed diffusion of molecules
• Pore size compatibility with the biological
  molecule
• Solubility of the biological molecule

There are two general methods of controlled drug
release
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Poly(ethylene glycol) pH Sensitive Hydrogels

• Advantages of PEG
• Biocompatibility Water soluble
• Non-toxic Rapid clearance from the body

N. A. Peppas et al. Journal of Controlled Drug
Release 62 (1999) 81-87
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Synthesis of Peg Hydrogel for Drug Delivery

• PEGDMA and PEGMA (with PEG MW1000) macromonomers
  were polymerized via free radical solution
  copolymerization in ratios ranging from 2080 to
  8020
• 1-Hydroxycyclohexyl phenyl ketone was added as a
  photoinitiator as 1 wt. of total monomers.

N. A. Peppas et al. Journal of Controlled Drug
Release 62 (1999) 81-87
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Success of PEG Hydrogel

• Diltiazem is a small MW drug with an effective
  hydrodynamic radius of 4.24Å
• It was demonstrated that as the pore size
  increased the diffusion rate of Diltiazem
  increased.

Fractional release of diltiazem in 1M
NaCl (different feed ratios of PEGDMA/PEGMA)
N. A. Peppas et al. Journal of Controlled Drug
Release 62 (1999) 81-87
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pH Sensitive Hydrogels based on Chitosan and
D,L-Lactic Acid

• Incorporation of a natural polymer into the gel
  aids in the bioactivity and biodegradability of
  the polymer
• The best method of combination is the graft
  copolymerization of the synthetic polymer onto
  the natural polymer.
• These hydrogels are currently being tested in
  controlled drug release mechanisms.
• Chitosan has received a lot of attention recently
  because it has been derivatized in the past and
  maintained its biocompatibility
• Cosmetics and biotechnology

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Graft Copolymerization of Lactic Acid onto
Chitosan
Xin, Qu. et al. Journal of Applied Polymer
Science, V.74, 3186-3192 (1999)
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Conclusions

• Hydrogels are network polymers that swell through
  a variety of mechanisms in an aqueous environment
  
• They have shown to be useful in medical
  applications as a mechanism of controlled release
• Other mechanisms of swelling
• pH, ionic strength, solvent composition, pressure
  and even electric fields