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Renee C' Smith1 and Paula T' Hammond2

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Toward Controlled Drug Delivery from Polyelectrolyte Multilayer Films ... Mara Macdonald. Helen Chuang. Kris Wood. Kris Stokes. Dan Schmidt ... – PowerPoint PPT presentation

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Title: 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.
5
Hydrolytically Degradable Films
Poly (ß?-amino ester) Polymer 1
Wood, et al. (2006) PNAS 103, 10207-10212
6
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
7
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

8
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

9
Exploration of Steric Hindrance
Increasing Steric Hindrance
10
Effect of Steric Hindrance
Release kinetics can be altered via sterics
11
Effect of Alkyl Chain Length
Increasing Alkyl Chain Length
12
Effect of Alkyl Chain Length
Release can be altered using chain length
13
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

14
Quantitative Measure of Hydrophobicity Octanol
Water Coefficient (LogP)
Increasing Steric Hindrance
Increasing Alkyl Chain Length
From Advanced Chemistry Development Software
15
Defining Boundaries


16
Defining Boundaries
Hydrophobicity can reduce film stability
17
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
18
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
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