1. Copyright 2006 © Mattioli Engineering All rights reserved TRANSDERMAL DELIVERY OF A SUBSTANCE COMPOSED BY HYALURONIC ACID AND AMINO ACIDS C. De Iulio, M. Mariotti, A. Massirone, N. Tamburlin, M. Triulzi

2. Copyright 2006 © Mattioli Engineering All rights reserved Needle therapy and alternative methods Nearby the traditional needle therapy there are new developing alternative methods that allow the transdermal delivery of ionic drugs and active substances without the use of needles.

3. Copyright 2006 © Mattioli Engineering All rights reserved Face and decolleté Bio Revitalization Bio Revitalization is one of the most requested treatments in esthetic medicine. Bio Revitalization is one of the most requested treatments in esthetic medicine. Some patients hardly stand the needle therapy. Some patients hardly stand the needle therapy. Face Bio Revitalization performed through alternative methods is raising a great interest. Face Bio Revitalization performed through alternative methods is raising a great interest.

4. Copyright 2006 © Mattioli Engineering All rights reserved Face Bio Revitalization with hyaluronic acid and amino acids through Dermoelectroporation® Our protocol was carried out using hyaluronic acid transdermally delivered without needles. Our protocol was carried out using hyaluronic acid transdermally delivered without needles.

5. Copyright 2006 © Mattioli Engineering All rights reserved Hyaluronic Acid Very Hygroscopic. Very Hygroscopic. Responsible of skin moisturizing. Responsible of skin moisturizing. Basic substance for the stabilization of collagen and elastic fibres. Basic substance for the stabilization of collagen and elastic fibres. Basic substance for metabolic exchanges and for process of repair and remodelling. Basic substance for metabolic exchanges and for process of repair and remodelling.

6. Copyright 2006 © Mattioli Engineering All rights reserved Hyaluronic Acid enriched with Amino Acids Ampoule: Ampoule: - Sodium Hyaluronate - Sodium Hyaluronate - water for injection - water for injection Freeze-dried bottle: Freeze-dried bottle: - Glycine - Glycine - L-Proline - L-Proline - L-Lysine Monohydrochloride - L-Lysine Monohydrochloride - Leucine - Leucine

7. Copyright 2006 © Mattioli Engineering All rights reserved Dermoeletctroporation® Transdermal Drug Delivey Dermoelectroporation® is a method for transdermal drug delivery that foresees: Dermoelectroporation® is a method for transdermal drug delivery that foresees: 1. A preventive microdermoabrasion with corundum crystals in order to lower the skin impedance in the interested part and to ease the transdermal transfer. 1. A preventive microdermoabrasion with corundum crystals in order to lower the skin impedance in the interested part and to ease the transdermal transfer. 2. The following delivery of the chosen substance through a pulsed iontophoresis with electrical waves similar to electroporation but with a lower and controlled intensity. 2. The following delivery of the chosen substance through a pulsed iontophoresis with electrical waves similar to electroporation but with a lower and controlled intensity.

8. Copyright 2006 © Mattioli Engineering All rights reserved Experimental analysis of the efficacy of transdermal delivery of hyaluronic acid through Dermoelectroporation® Università Degli Studi di Firenze D.ssa S. Pacini, Dr. M. Ruggero Rat skin treated by Dermoelectroporation® and fluorescent hyaluronic acid.

9. Copyright 2006 © Mattioli Engineering All rights reserved Performed Protocol 10 patients – age between 30 and 59 years old 10 patients – age between 30 and 59 years old 1 treatment per week for 4 weeks 1 treatment per week for 4 weeks 1 treatment: microdermabrasion on the interested area + delivery of 3 ml hyaluronic acid enriched with amino acids. 1 treatment: microdermabrasion on the interested area + delivery of 3 ml hyaluronic acid enriched with amino acids.

10. Copyright 2006 © Mattioli Engineering All rights reserved Evaluation Diagram MoisturizingElasticityToneCompactness BeforeAfterBeforeAfterBeforeAfterBeforeAfter Pt. 1+++++++++++++ Pt. 2+++++++++++++++++++++++++++ Pt. 3++++++++++++++++ ++++ Pt. 4++++++++++++++++++++++++++++ Pt. 5++++++++ ++++++++ Pt. 6++++++++++++++++++++++++++ Pt. 7++++++++++++++++++++++ Pt. 8++++++++++++++++ ++++++++++++ Pt.9++++++++++++++++++++++++ Pt. 10++++++++++++++++++++++++++++++ Evaluations carried out also with the aid of a skin check up system Very good = +++++ Good = ++++ Medium = +++ Sufficient = ++ Poor = +

11. Copyright 2006 © Mattioli Engineering All rights reserved Before After

12. Copyright 2006 © Mattioli Engineering All rights reserved Before After

13. Copyright 2006 © Mattioli Engineering All rights reserved Results In all patients we could notice a brighter and more tonic skin. Patients were satisfied both for the results and for the pleasantness of the treatment, also thanks to the relaxing vibratory massage made by the probe delivering the impulses.

14. Copyright 2006 © Mattioli Engineering All rights reserved Conclusions The combined action of microdermabrasion, together with the revitalizing action of hyaluronic acid delivered through dermoelectroporation without the use of needles, obtained more interesting results compared to the use of the same substance with needle therapy. 1. The peeling performed with microdermabrasion eases the transfer of hyaluronic acid and increases the quality and brightness of the skin. 2. The probe for the delivery of hyaluronic acid allows the delivery of the substance in an uniform way. The method was pleasant for the patient, easy to perform and without consequences like bruises, redness, irritations and pain.