MATTIOLI Engineering

In 2004, Mattioli Engineering introduced a new

concept in dermatology for the transdermal

delivery of high-molecular-weight therapeutics

up to 1,000 kDa. The patented, proprietary technology,

known as Dermoelectroporation® (DEP)

is shown in Figure 1 and 2. The DEP system

delivers controlled current pulses between two

adjacent electrodes to increase the permeability

of the skin. The effect of the electrical pulses

is the opening of water-based microchannels

through stratum corneum and epidermis.

Thus a high-molecular-weight drug filled

into two adjacent gauze-pad electrodes is then

delivered into the dermis. Sonic technology is

also employed to enhance delivery.

The device is covered by a broad US patent

estate, which includes US patent numbers:

6518538; 6535761; 6587730; 6687537;

6743215; 6748266; 6980854; 7010343;

7083580; 7376460; 7471979; 7496401;

7520875; 7532926; and 7945321.

The device is EU CE marked and US FDAcleared

for the transdermal delivery of lidocaine.

Many other drugs are successfully deliverable,

although not yet FDA-approved. These

include: Botulinum toxin, phosphatidylcholine,

aminophylline, L-carnitine, amino acids, heparin,

collagen, various vitamins, various steroids,

diclofenac and others.

To date, the technology has been used mainly

in cosmetic dermatology for delivering sub-

In this article, Gian Franco Bernabei, PhD, Chief Executive Officer, Mattioli Engineering,

introduces the company’s transdermal drug delivery system for the delivery of large molecules

using electroporation.

THE DERMOELECTROPORATION® SYSTEM

FOR TRANSDERMAL DELIVERY OF DRUGS

Dr Gian Franco Bernabei

Chief Executive Officer

T: +39 055 882247

F: +39 055 8874879

E: info@mattioliengineering.com

Mattioli Engineering Italia S.p.a.

Via Petrarca 80/82

50041 Calenzano (FI)

Italy

www.mattioliengineering.com

“INSTEAD OF USING THE STANDARD ELECTROPORATION

HIGH-VOLTAGE CONTROLLED PULSES, THAT COULD DAMAGE

THE SKIN DUE TO THE UNPREDICTABLE CURRENT DENSITY,

DEP APPLIES CONTROLLED CURRENT PULSES TO THE SKIN”

Figure 1: The Dermoelectroporation®

(DEP) System.

stances like non-crosslinked hyaluronic acid,

in conjunction with a microdermabrasion treatment.

The microdermabrasion treatment is a

standard in cosmetic dermatology and it is needed

in order to have the assurance that the stratum

corneum has a maximum permeability so that

that the drug is really transdermally delivered.

The DEP technology developed by Mattioli

is an improvement on the standard electroporation

pulse systems that have been in use for

more than a decade and are known to be able

to deliver macromolecules through stratum corneum

and epidermis.

Instead of using the standard electroporation

high-voltage controlled pulses, that could damage

the skin due to the unpredictable current

density, DEP applies controlled current pulses

to the skin. This technology works perfectly

if the permeability of the stratum corneum is

enough to enable transdermal transport.

In dermatology it is normal practice to use

microdermabrasion in order to pretreat the skin

for further treatment and thus has not been a

problem to introduce this limitation also because

Mattioli is one of the major manufacturers of

microdermabrasion equipment. The reason pretreatment

is included is that we limit to 100V the

maximum voltage that the device applies to the

skin, in order to avoid adverse effects.

Recently, in order to broaden the use of the

technology, a means to verify sufficient stratum

corneum permeability has been added to the

equipment. This is done by measuring the electrical

impedance of the skin during the current

pulse. This makes it possible to check if pretreatment

is needed and, further, to judge whether

full microdermabrasion pretreatment is required

or whether simpler pretreatment using scrubs or

even gently abrasive paper would suffice.

The DEP comprises a machine body and

a handpiece. On the handpiece is mounted

an optional computerised liquid dispenser that

delivers the drug to the disposable cap by pushing

a disposable drug-loaded syringe (see Figure 3).

Two sizes of syringes (10 cm3 and 20 cm3) and

two handpiece sizes (small and large) are available.

The typical injection speed over a skin

surface of 30 cm2 is between 0.5-1 cm3/min,

depending on drug and handpiece size.

The device has been validated in a number

of clinical studies conducted by the Department

of Anatomy at the University of Florence, Italy.

Amongst the many studies that have used the

device, some of the most significant include:

• Pacini S, Punzi T, Gulisano M,

“Transdermal delivery of Hyaluronic

acid”. J of Dermatol Sci, 2006, Vol 44,

pp 169-171.

• Pacini S, Punzi T, Gulisano M, “Transdermal

delivery of Clostridium Botulinum Toxin

Type A by pulsed current Iontophoresis”.

Poster Presented at 65th Annual Meeting

of the American Academy of Dermatology,

2007, Washington DC, US.

• Pacini S, Punzi T, Gulisano M, Cecchi F,

Vannucci S, Ruggiero M, “Transdermal

delivery of heparin using pulsed current

inotophoresis”. Pharm Res, 2006, Vol

23(1), pp 114-120.

• Pacini S, Peruzzi B, Gulisano M,

“Qualitative and quantitative analysis of

transdermic delivery of different biological

molecules by iontophoresis”. Ital J Anat

Embryol, 2003, Vol 18(Suppl2), pp 127–129

• Pacini S, Peruzzi B, Gulisano M et al,

“Transdermal delivery of heparin by

means of alternate current skin electroporation”.

Ital J Anat Embryol, 2004, Vol

109(1), p 223.

• De Bartolo HM, “Comparison of Mattioli

Iontophoresis, Mesosystems, the U225,

and Manual Injections”. Proceedings of

the Illinois Society of Ophtalmology &

Otolaryngology, 2005, Vol 9(1).

• De Bartolo HM, “Scar Revision &

Minimally Invasive Cosmetic Surgery using

Mattioli Engineering Technology”, ibid.

• BacciPA,“TheroleofDermoelectroporation”.

Cellulite: Pathphysiology & Treatment, 2006,

Chapter 18, pp 291-299. (Published by Taylor

& Francis, ISBN-10: 0-8247-2985-4/ISBN-

13: 978-0-8247-2985.)

Figure 2: The Dermoelectroportation®

(DEP) System and Mobile Stand.

Figure 3: On the DEP handpiece is mounted an optional computerised liquid dispenser

that delivers the drug to the disposable cap by pushing a disposable drug-loaded syringe.

www.mattioliengineering.com

New Transderm® Ionto

DEP System

The only and Real transportable

Needles free Syringe for any skin need.

* Dermoelectroporation® is a patented technology from Mattioli Engineering

clinically proven to be able to transdermally deliver an accurate dosage

of high molecular weight drugs into the body due to controlled electrical pulses.

CAUTION: Federal law (USA) restricts this medical device to sale

by or on order of a physician.

** Transdermal delivery of Clostridium botulinum toxin type A

by pulsed current iontophoresis

S. Pacini M.D., M. Gulisano M.D., T. Punzi PhD.,

(Department of Anatomy, Histology and Forensic Medicine,

Viale Morgagni 50, University of Firenze, 50134 Firenze, Italy)

M. Ruggiero M.D.

(Department of Experimental Pathology and Oncology,

Viale Morgagni 85, University of Firenze, 50134 Firenze, Italy)

New Delivery caps:

• 30% efficiency enhanced

• Faster then ever

• Avoids unwanted waste of products

• More comfort during session

a new science in skin care™

BEFORE AFTER

The new improved Transderm® Ionto DEP System represents

the only one and real transportable “Needles free Syringe” System

on the market carrying Dermoelectroporation® technology*.

The new improved Transderm® Ionto DEP System introduces:

• A New “Syringe like” handpiece design for medical controlled

transdermal delivery of any ionic drug solution doctors indicate.

• Optimized MACRO molecules transdermal delivery

(up to 2,000.000dalton-type a botulinum toxine** included).

• Continuos Visual indication on the skin absorption.

• Real time control on the whole treatment

(delivery time, volume, flow, skin absorption).

MATTIOLI ENGINEERING ITALIA

Via Petrarca 80-82

50041 Calenzano (Firenze) - Italy

Tel. (+39) 055 882247 - Fax (+39) 055 8874879

info@mattioliengineering.com