Interface Effects in High Volume Nanoscale Processing of Polymers

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MicroFluidics Technology Fair
Nanoemulsion Delivery of
Pharmaceutical, Nutraceuticals
and Cosmeceuticals In vitro and In vivo
studies October 3, 2006
Center for Health and Disease Research
Robert J Nicolosi - Director
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Illustration of a Nano-Emulsion
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Characteristics of Nanoemulsions

• Stable at temperatures up to 110 C and from pH lt
  2.0 8.0
• 6 month stability (at least)
• Range of particle sizes (25-100 nm)
• Converts fat soluble chemicals to stable water
  dispersions

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Nanoemulsions of Tocopherol
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Does Size make a difference in
Efficacy of Delivering Tocopherol as a
Micro (10-6) vs Nanoemulsion (10-9)
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Vitamin E Enhancing Bioactivity
Microemulsion vs.NanoEmulsifion
Reactive Oxygen Species (ROS)
Nanoemulsions of Vitamin E are 100 times more
active than Microemulsion Encapsulated Vitamin E
in cell culture.
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Transdermal Delivery of Tocopherol Effect on
Blood Levels in Hamsters (n7)
3.7 ug/mL Tocopherol
Tocopherol alone
Nanoemulsion Of Tocopherol
2.09 ug/ml Tocopherol
µg/mL
1 2
3
(Submitted 2006)
Hours
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Nanoemulsion delivery of anti-
inflammatory agent Aspirin in mice
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(JACS 2005)
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Anti-oxidant Synergy Formulation suppresses
malignancy Nanoemulsions improve its
effectiveness in culture
Taxol

• ASF forces differentiation of neuroblastoma (most
  common solid tumor in children)...Like neurons,
  if they begin to differentiate, they no longer
  multiply

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ASF Studies (In vivo)

• Nude Mice
• since they lack a fully-functional immune system
• Injection of Cancer Cells
• by subcutaneous injection of Mouse or Human
  Cancer cells (300,000 cells /ml)
• Injection of ASF solution
• once tumors were detected
• Measure the tumor diameter
• quantified daily in accordance with the longest
  diameter

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The neuroblastoma in the nude mice
Tumor
Control (no treatment)
No Tumor
ASF Nano-emulsion
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Subcut Injection vs Topical Delivery of ASF
containing- nanoemulsions on
neuroblastomainduced
tumor growth rate.
- 4
- 65 - 63

Subcut inj Subcut inj
Transdermal
( In press 2006)
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Nanoemulsion delivery of Tamoxifen to
breast cancer cell lines
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The Effect of Tamoxifen (T) and a
Nanoemulsion Preparation of Tamoxifen (NT) on
Cell Proliferation
C
T
NT
1 3 5 7
10 12
Days of Culture
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Dacarbazine Nano-emulsion Treatment in a
Zenograft Melanoma Mouse Model
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Tumor Reduction with Nano preparations of
Dacarbazine
p lt 0.0007
P lt 0.000003
P lt0.0001
10x
- 4
2x
- 30
- 49
- 62
Nano
Control Dacarbazine
Dacarbazine
Topical IM Topical IM
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Tumor Growth in Mice after Dacarbazine
Administration is Stopped for 12 Weeks
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Control Drug
Topical
- 18
- 23
- 92
Drug Nano-Drug IM
Topical
Nano-Drug IM
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Anti-Bacterial indication of
Nanoemulsions
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Microemulsion versus Nanoemulsion of Soy Protein
Nanoemulsified
Homogenized
Nanoemulsions are stable dispersions which do not
agglomerate and which demonstrate antimicrobial
activity
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Gram Staph Aureus Bacteria
Staph Aureus Control
Staph aureus streaked
empty
nanoemulsion

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• Summary
• Nanoemulsion technology produces
• particle sizes in the 25-100 nm range.
• The technology converts fat soluble to
• water soluble compounds.
• The technology can deliver pharmaceuticals,
• nutraceuticals and cosmeceuticals.
• The particle size reduction is associated
• with increased bioavailability and efficacy.

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Acknowledgements Doctoral Students
in the Biomedical Engineering Biotechnology
Program Jean-Bosco Tagne Srikanth
Kakumanu Fongshu Kuo Balaji Karthick Rohini
Vishwanathan Mukta Bagul Microfluidics (MFIC)
Corp, Newton MA 02469