Robert J Nicolosi - Director

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

The inner core The inner core consisting of any consisting of any

oiloil

Drug or nutrient Drug or nutrient molecules within molecules within the corethe core

The emulsifier The emulsifier layer surrounding layer surrounding the nano-particle. the nano-particle.

Illustration of a Nano-Emulsion

Nanoparticles (via AFM))

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

Nanoemulsions of Tocopherol

Does Size make a difference in Efficacy of Delivering Tocopherol as a Micro (10-6) vs Nanoemulsion (10-9)

Vitamin E Enhancing Bioactivity: Microemulsion vs.NanoEmulsifion

Nanoemulsions of Vitamin E are 100 times more active than Microemulsion Encapsulated Vitamin E in cell culture.

Rea

ctiv

e O

xyg

en S

pec

ies

(RO

S)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

Hours1 2 3

μg

/mL

NanoemulsionOf Tocopherol

Tocopherol alone

3.7 ug/mL Tocopherol

2.09 ug/ml Tocopherol

Transdermal Delivery of Tocopherol:Effect on Blood Levels in Hamsters (n=7)

(Submitted 2006)

Nanoemulsion delivery of anti- inflammatory agent Aspirin in mice

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

The Anti-inflammatory properties of Nanoemulsion Containing Aspirin in CD-1 Mice

-61%

-25%

Aspirin+

Nano-emulsionAlone

AspirinControl

mill

imet

ers

(JACS 2005)

““Anti-oxidant Synergy Formulation” Anti-oxidant Synergy Formulation” suppresses malignancy: Nanoemulsions suppresses malignancy: Nanoemulsions

improve its effectiveness in cultureimprove its effectiveness in culture

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

Taxol

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

The neuroblastoma in the nude mice

ASF Nano-emulsion

Control (no treatment)

Tumor

No Tumor

Subcut Injection vs Topical Delivery of ASF containing-

nanoemulsions on neuroblastoma–induced

tumor growth rate.

Subcut inj Subcut inj Transdermal

- 65% - 63%

( In press 2006)

- 4%

Nanoemulsion delivery of Tamoxifen to breast cancer cell lines

0

20

40

60

80

100

120

140

160

Cel

l Pro

lifer

atio

n

B Control C Tamoxifen D Nano-Tamoxifen

1 3 5 7 10 12

Days of Culture

The Effect of Tamoxifen (T) and a NanoemulsionPreparation of Tamoxifen (NT) on Cell Proliferation

C

T

NT

Dacarbazine Nano-emulsion Treatment in a Zenograft Melanoma Mouse Model

0

1

2

3

4

5

6

7

8

Tu

mo

r S

ize

(mm

)

Control Dacarbazine Dacarbazine

Topical IM Topical IM

- 4%

- 30%

- 49%

- 62%

p < 0.0007 P < 0.000003 P <0.0001

10x

2x

Tumor Reduction with Nano preparations of Dacarbazine

Nano

-100

-80

-60

-40

-20

0

20

40

Tu

mo

r G

row

th (

mm

)

Tumor Growth in Mice after Dacarbazine Administration is Stopped for 12 Weeks

Control Drug Topical

Drug Nano-Drug

IM Topical

Nano-Drug

IM

+ 43%

+ 30%

- 18% - 23% - 92%

Anti-Bacterial indication

of Nanoemulsions

Microemulsion versus Nanoemulsion of Soy Protein

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

Homogenized Nanoemulsified

Staph Aureus Control Staph aureus streaked empty nanoemulsion

Gram + Staph Aureus Bacteria

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.

Acknowledgements

Doctoral Students in the Biomedical Engineering & Biotechnology Program

Jean-Bosco Tagne Srikanth KakumanuFongshu Kuo Balaji KarthickRohini Vishwanathan Mukta Bagul

Microfluidics (MFIC) Corp, Newton MA 02469