Banca de DEFESA: Camila Oliveira Cardoso

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Camila Oliveira Cardoso
DATE: 29/08/2025
TIME: 14:00
LOCAL: https://conferenciaweb.rnp.br/webconf/guilherme-martins-gelfuso
TITLE:

“DACARBAZINE FOR THE TOPICAL TREATMENT OF MELANOMA: EFFECT OF IONTOPHORESIS IN ENHANCEMENT OF SKIN PENETRATION”

KEY WORDS:

“dacarbazine; melanoma; topical administration; iontophoresis.”

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

“Dacarbazine (DTIC) is the standard chemotherapy drug for the systemic treatment of melanoma, an invasive and aggressive form of skin cancer. However, its intravenous administration is related to several adverse effects, which could be overcome by topical application. Considering obstacles to the topical application of the drug, such as low stability and limited skin penetration, this work proposes to evaluate the effect of iontophoresis on the topical administration of DTIC. Initially, an analytical method using high-performance liquid chromatography was validated for quantifying the drug in the presence of skin contaminants. A reversed-phase C18 column was used as the stationary phase, and gradient elution of a mobile phase consisting of methanol and sodium phosphate monohydrate buffer pH 6.5 (0.01 mol/L) at a flow rate of 1.0 mL/min was implemented. DTIC was detected at 364 nm. The method was selective against cutaneous interferents, linear (r = 0.9995) in a concentration range of 1.0–15.0 μg/mL, accurate with an overall coefficient of variation less than 3.8%, accurate recovering between 91 -112% of the drug present in the skin layers, and sensitive with a detection limit of 0.10 μg/mL and a quantification limit of 0.30 μg/mL. Next, the skin permeation of the drug was evaluated with iontophoretic application. The electrical stability of the drug was evaluated before the iontophoretic experiments. Three current profiles (0.10, 0.25 and 0.50 mA/cm2) were tested through in vitro tests using porcine ear skin and diffusion cells, in which DTIC permeation was evaluated in solution and in solution. containing an antioxidant for 6 h. The results suggested that the instability of DTIC in the presence of current requires the use of an antioxidant that prevents its degradation. Different levels of current density can modulate and influence the extent of drug penetration and permeation. Furthermore, the presence of a competing ion, such as the added antioxidant metabisulfite, can reduce drug permeation under the low current of 0.10 mA/cm2. However, when increasing the current density to 0.25 mA/cm2 and 0.50 mA/cm2, the skin deposition of the drug increased considerably (p≤0.0001). Finally, the effect of DTIC on melanoma cell lines (MeWO and WM) was investigated after drug exposure and drug application of iontophoresis, after incubation for 72 h. The application of iontophoresis in cell cultures only decreased cell viability in the WM lineage at a concentration of 0.0125% of DTIC. The MeWo lineage was more sensitive to treatment: after application of 0.00625% DTIC, only 25% viable cells were found in each condition, while 45% viable cells were found in the WM lineage. The IC50 values were 0.0032% and 0.0037%, without and with electric current in the MeWo lineage, and 0.0079 and 0.0064% without and with electric current, in the WM lineage. Thus, it is partially concluded that the application of iontophoresis as a permeation promoter is a promising alternative to promote the topical application of DTIC for the treatment of superficial cancers, such as melanoma. This more targeted therapeutic option could, in addition to increasing the bioavailability of the active ingredient, reduce the adverse effects of this therapy.”

COMMITTEE MEMBERS:
Presidente - 1880131 - GUILHERME MARTINS GELFUSO
Externa à Instituição - LETÍCIA SCHERER KOESTER - UFRGS
Interna - 1562111 - PEROLA DE OLIVEIRA MAGALHAES DIAS BATISTA
Externa à Instituição - STEPHÂNIA FLEURY TAVEIRA - UFG
Externa ao Programa - 1969280 - TAIS GRATIERI - null