Renee C' Smith1 and Paula T' Hammond2

1
Toward Controlled Drug Delivery from
Polyelectrolyte Multilayer Films

• Renee C. Smith1 and Paula T. Hammond2
• Department of Chemistry1, Department of Chemical
  Engineering2
• Massachusetts Institute of Technology

Division of Colloid and Surface Chemistry 8/19/07
2
Outline

• Combination Devices
• Layer-by-Layer Assembly
• Hydrolytically Degradable Films
• Impact of Structure on Release
• Conclusions

3
Combination Devices

• Drug delivery from functional prosthetic implants
• Controlled drug release at pathological site
• Mitigation of device associated complications

4
Layer-by-Layer Assembly

• Electrostatic assembly
• Mild, aqueous dipping conditions
• Precise control of film architecture
• Capable of concurrent and sequential release

Decher. Science.1997,277,1232-1237.
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Hydrolytically Degradable Films
Poly (ß?-amino ester) Polymer 1
Wood, et al. (2006) PNAS 103, 10207-10212
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Previous Research

• Influence of structure
• Polystyrene sulfonate
• Hydrophobicity
• Charge density
• Alkyl chain length
• ? Hydrophobicity ? Rate
• Alternating layers allow for additional control

Zhang, et al. Langmuir 2006, 22, 239-245
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Research Goal

• To what extent can structural manipulation be
  used to control release rates and duration in
  hydrolytically degradable LBL films?
• What are the boundaries?
• Why do they exist?
• Better model biological systems

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Methodology

• Series of Poly(ß-amino esters)
• Growth, degradation and release with dextran
  sulfate as the polyanion
• Release (PolyX /14C-dextran sulfate)20
• Phosphate buffer solution 25C
• 1 mL aliquots at various times
• Radioactivity measured via scintillation counting

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Exploration of Steric Hindrance
Increasing Steric Hindrance
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Effect of Steric Hindrance
Release kinetics can be altered via sterics
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Effect of Alkyl Chain Length
Increasing Alkyl Chain Length
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Effect of Alkyl Chain Length
Release can be altered using chain length
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Anomalous Behavior of Poly 5 6

• Sterics interfere with formation of ionic x-links
  
• Low charge density reduces film stability
• Hydrophobicity of polymer reduces film stability

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Quantitative Measure of Hydrophobicity Octanol
Water Coefficient (LogP)
Increasing Steric Hindrance
Increasing Alkyl Chain Length
From Advanced Chemistry Development Software
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Defining Boundaries


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Defining Boundaries
Hydrophobicity can reduce film stability
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OctanolWater Coefficient Relationship
2
2
7
1
7
7
1
1
3
9
3
9
3
5
8
6
5
8
6
5
8
6
Release duration can be estimated via logP
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Conclusion

• Determined correlation between release and
  structure of poly(ß-amino esters)
• Allows the tailoring of
• Release kinetics
• Mechanical properties
• Address issues of biocompatibility
• Future work
• Determine minimum LogP needed for instability
• Test mechanical properties of films
• Expand to different therapeutics

19
Acknowledgements

• Prof. Hammond
• Hammond Group
• Mara Macdonald
• Helen Chuang
• Kris Wood
• Kris Stokes
• Dan Schmidt
• Bell Labs Graduate Research Fellowship and NIH
  for funding

20
Questions