Home » Key Clinical Research Articles Global Medical Discovery » Optimization of photodynamic therapy using negative pressure

Optimization of photodynamic therapy using negative pressure

Significance Statement

In this paper we have intention to development new approaches to improve the Photodynamic therapy using topical ALA.  The transdermal drug delivery as an alternative to oral medications and hypodermic injections shows advantages as a localized and non-systemic application. However there are any limitations in the transdermal application of aminolevulinic acid (ALA) related to low penetration and uniformity of Protoporphyrin IX (PPIX) formation at skin. Many strategies are being discussed in the literature to increase the permeation of ALA through to skin as following: 1) modification in the physical chemistry characteristics of ALA creating new molecules from ALA, 2) modification in the characteristics of emulsion, where ALA is introduced, considering the type of emulsion, related to phases water in oil or Oil in water or in relation to particle size (microemulsions and nanoemulsions), 3) new proposal of encapsulation of ALA using nanoparticle and microparticle delivery systems and finally the application of new technologies involving physical methods as microneedles, iontophoresis, electroporation, ultrasound, ablation lasers systems, dermabrasion and combinations. Here, we propose to demonstrate a new alternative to perform ALA- photodynamic therapy using a mechanical device (vacuum prototype) sufficient to induce the negative pressure at skin, increasing the protoporphyrin IX formation at skin, in amount and homogeneity. Also, in the results found to group using the vacuum prototype, the formation and elimination of PPIX being an advanced in the treatment, reducing treatment time, cost and side effects of a cutaneous photosensitivity. The evaluations at skin were performed using widefield fluorescence imaging and fluorescence spectroscopy to superficial analyses and deeper analyses at skin. In agreement with the results, the induction of negative pressure can be useful as more one tool to be applied immediately in the photodynamic therapy  procedure.

Figure 1:  A) autofluorescence of human skin, Fluorescence of Protoporphyrin IX at human skin after 3h with ALA cream incubation (B) Fluorescence of Protoporphyrin IX at human skin after 3h with ALA cream incubation  in the presence of vaccum prototype.

Optimization of photodynamic therapy using negative pressure

 

 

 

 

 

Figure 2:  A) Fluorescence of Protoporphyrin IX at human skin after 3h with ALA cream incubation (B) Fluorescence of Protoporphyrin IX at human skin after 3h with ALA cream incubation  in the presence of vaccum prototype.

Optimization of Photodynamic Therapy Using Negative Pressure22

Journal Reference

Menezes PF, Requena MB, Bagnato VS.

Photomed Laser Surg. 2014 May;32(5):296-301.

Instituto de Física de São Carlos (IFSC), University of São Paulo (USP) , São Carlos – SP, Brazil .

 

Abstract

OBJECTIVE:

The goal of this study is to demonstrate an alternative procedure to perform topical photodynamic therapy (PDT). Here, we propose the combined use of negative pressure and a 5-Aminolevulinic acid (5-ALA) cream occlusion to increase protoporphyrin IX (PPIX) formation.

BACKGROUND DATA:

photodynamic therapy  using topical 5-ALA as a prodrug and precursor of PPIX has been used in the treatment and diagnosis of different types of cancer and skin diseases. The use of 5-ALA offers many advantages as a localized and non-systemic application, but it shows limitations in relation to skin penetration. Many authors have discussed the limitations of 5-ALA penetration through the skin. The skin penetration of 5-ALA can be optimized using mechanical devices associated with typical PDT procedure.

METHODS:

For this study, 20% 5-ALA cream was applied to a 9 cm(2) area of skin, and an occlusive dressing was placed. The PPIX production was collected at the skin surface, using fluorescence spectroscopy and widefield fluorescence imaging, for 7 h, and after 24 h.

RESULTS:

We observed that in the presence of negative pressure therapy, the PPIX production, distribution, and elimination are greater and faster than in the control group. The PPIX formation was ∼30% in deeper skin layers, quantified by fluorescence spectroscopy analysis, and ∼20% in surface skin layers, quantified by widefield fluorescence imaging analysis.

CONCLUSIONS:

Negative pressure induction can also help photodynamic therapy  application in the case of inefficient PPIX production. These results can be useful for optimizing the photodynamic therapy .

Go To  PubMed