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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. Illustration of a Nano-Emulsion.

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slide1

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

slide2

Illustration of a Nano-Emulsion

Nanoparticles (via AFM))

  • The inner core consisting of any oil
  • Drug or nutrient molecules within the core
  • The emulsifier layer surrounding the nano-particle.
slide3

Characteristics of Nanoemulsions

  • Stable at temperatures up to 110° C and from pH < 2.0 – 8.0
  • 6 month stability (at least)
  • Range of particle sizes (25-100 nm)
  • Converts fat soluble chemicals to stable water dispersions
slide5

Does Size make a difference in

Efficacy of Delivering

Tocopherol as a Micro (10-6)

vs Nanoemulsion (10-9)

slide6

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.

slide7

Transdermal Delivery of Tocopherol:

Effect on Blood Levels in Hamsters (n=7)

3.7 ug/mL Tocopherol

Tocopherol alone

Nanoemulsion

Of Tocopherol

2.09 ug/ml Tocopherol

μg/mL

1 2 3

(Submitted 2006)

Hours

slide8

Nanoemulsion delivery of anti-

inflammatory agent Aspirin in mice

slide10

“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
slide11

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
slide12

The neuroblastoma in the nude mice

Tumor

Control

(no treatment)

No Tumor

ASF

Nano-emulsion

slide13

Subcut Injection vs Topical Delivery of ASF containing-

nanoemulsions on neuroblastoma–induced

tumor growth rate.

- 4%

- 65% - 63%

Subcut inj Subcut inj Transdermal

( In press 2006)

slide14

Nanoemulsion delivery of Tamoxifen

to breast cancer cell lines

slide15

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

slide16

Dacarbazine Nano-emulsion Treatment

in a Zenograft Melanoma Mouse Model

slide17

Tumor Reduction with Nano preparations of Dacarbazine

p < 0.0007

P < 0.000003

P <0.0001

10x

-4%

2x

- 30%

- 49%

- 62%

Nano

Control Dacarbazine Dacarbazine

Topical IM Topical IM

slide18

Tumor Growth in Mice after Dacarbazine

Administration is Stopped for 12 Weeks

+ 43%

+ 30%

Control Drug

Topical

- 18%

- 23%

- 92%

Drug Nano-Drug

IM Topical

Nano-Drug

IM

slide20

Microemulsion versus Nanoemulsion of Soy Protein

Nanoemulsified

Homogenized

Nanoemulsions are stable dispersions which do not agglomerate and which demonstrate antimicrobial activity

slide21

Gram + Staph Aureus Bacteria

Staph Aureus Control Staph aureus streaked

empty nanoemulsion

slide22

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.
slide23

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