1. Copyright 2004 © Mattioli Engineering All rights reserved Transdermal Delivery Technology

2. Limits of existing Technology Traditional Ionthophoresis Ineffective for high weight molecules Changes the pH of ionic drug solutions Electrolytic effect at the electrodes Electrolysis of the ionic solution Microdermabrasion Low delivery rate Effects limited to the skin surface Electroporation High peak currents High risk of skin damage Adverse effects

3. Limits of existing Technology Ultrasounds Ineffective for high weight molecules Microcurrents Very Low delivery rate Not validated for medical application Topical Application (Patches) Low delivery rate Adverse effects

4. Mattioli Engineering’s Solution Mattioli Engineering removes the limits… combines the advantages of the existing technologies to create the Transderm® Ionto system

5. Mattioli Engineering’s Solution How does Transderm Ionto System works: 1 st Step: Ultrapeel® Microdermabrasion 2 nd Step: Transderm® Ionto system Using Dermoelectroporation® Technology

6. DERMOELECTROPORATION® DERMOELECTROPORATION® means: DERMa Dermo = From preventive MicroDERMabrasion. Electroporation = From the shape of the electrical pulses of -low current - max 5mA- delivered on the dermis after microdermabrasion.

7. DERMOELECTROPORATION® DERMOELECTROPORATION® features: IONTOPHORESIS “Electroporation-like” pulsed IONTOPHORESIS with safe, current-limited, pulsed waveforms (low current - max 5mA) RETURN ELECTRODE around the ionic drug solution delivery electrode and not separated as in traditional Ionthophoresis systems.

8. DERMOELECTROPORATION®

9. Results of DERMOELECTROPORATION® Ionic solution of low-weight molecules Equivalent to classic Iontophoresis, but without direct current Transdermal delivery of: Ionic solution of high-weight molecules “Electroporation-like” Transdermal delivery prior Microdermabrasion required

10. Advantages of Transdermal Delivery of Low-Weight Molecules Positive and negative ions of the drug are transdermally delivered at the same time No electrolytic reactions at the electrodes No change of ionic drug solution pH No electrolysis of ionic drug solution Less skin irritation Possibility for prior microdermabrasion to enhance transdermal delivery European Clinical tests demonstrate advantages of Dermoelectroporation® Vs. Iontophoresis for transdermal delivery of radioactive Lidocaine

11. Advantages of Transdermal Delivery of High-Weight Molecules No skin damage due to low limited-current pulses No change in pH due to symmetrical pulse administration No adverse effects reported European Clinical tests demonstrate enhanced delivery of collagen and a five-fold increase in transdermal delivery of Eparine using Dermoelectroporation® Vs. application on the skin

12. Advantages of Dermoelectroporation®

13. TRANSDERM® IONTO

14. EUROPEAN EXPERIENCES Biorestoration Carnitine Collagen Lidocaine Rehabilitation

15. Transderm ® Ionto Distributed by: Saratoga Aesthetics 1-800-998-1555 Email: cfkusa@aol.com