Banca de QUALIFICAÇÃO: Camila Oliveira Cardoso

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : Camila Oliveira Cardoso
DATE: 08/03/2024
TIME: 14:00
LOCAL: Plataforma Virtual - ConferênciaWeb
TITLE:

DACARBAZINE FOR THE TOPICAL TREATMENT OF MELANOMA: EFFECT OF IONTOPHORESIS AND NANOENCAPSULATION IN ENHANCEMENT OF SKIN PENETRATION

KEY WORDS:

dacarbazine; melanoma; topical administration; iontophoresis; polymeric nanoparticle.

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

Dacarbazine (DTIC) is the standard chemotherapeutic drug used for the systemic treatment of melanoma, an invasive and aggressive form of skin cancer. However, its intravenous administration is related to several side effects, which could be overcome by topical application. This project proposes to evaluate the effect of iontophoresis and nanoencapsulation on the topical administration of DTIC. Initially, an analytical method using high-performance liquid chromatography (HPLC) was validated to quantify the drug in the presence of skin contaminants. A reversed-phase C18 column was used as a stationary phase, and gradient elution of a mobile phase consisting of methanol and pH 6.5 sodium phosphate monohydrate buffer (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 skin interferents, linear (r = 0.9995) in a concentration range of 1.0–15.0 μg/mL, precise with an overall variation coefficient lower than 3.8%, accurate achieving recovery from the skin layers within 91-112%, and sensitive with detection limit of 0.10 μg/ mL and quantification limit of 0.30 μg/mL. Next, drug permeation studies with iontophoretic application were evaluated. The electrical stability of the drug was evaluated prior to the iontophoretic experiments. Three current profiles (0.10; 0.25 and 0.50 mA/cm2) were tested through in vitro tests using porcine ears skin and vertical, flow-through diffusion cell, in which DTIC permeation was evaluated in solution and in solution with an antioxidant during 6 h. Results suggested that the instability of DTIC in the presence of the current requires the use of an antioxidant that prevents its degradation. Different levels of current density can modulate and influence the extension of drug penetration and permeation, moreover, the presence of a competing ion can reduce drug permeation under the low current of 0.10 mA/cm2. However, by increasing the current density to 0.25 mA/cm2 and 0.50 mA/cm2, the drug delivery increased considerably (p≤0.0001).Finally, the effect of DTIC against skin cancer cells (MeWO and WM) was investigated after exposure of the drug and of the drug and iontophoresis, and after 72 h of incubation. The application of iontophoresis in cell cultures only decreased cell viability in the WM cell line at a concentration of 0.0125% of DTIC. The MeWo cell line was more sensitive to treatment, after application of 0.00625% DTIC, only 25% of viable cells were calculated in each condition, while 45% were calculated in the WM cell line. The IC50 values were 0.0032% and 0.0037%, without and with electric current, in the MeWo cell line, and 0.0079 and 0.0064% without and with electric current, in the WM cell line. Thus, the application of iontophoresis as a permeation promoter is a promising alternative for the development of a topical formulation for the treatment of superficial cancers. This more targeted therapeutic option could increase the bioavailability of the active ingredient, and reduce the adverse effects of this therapy.

COMMITTEE MEMBERS:
Presidente - 1880131 - GUILHERME MARTINS GELFUSO
Externa ao Programa - 1529483 - MARIA DE FATIMA BORIN - nullExterna à Instituição - RENATA FONSECA VIANNA LOPEZ - USP
Externa ao Programa - 1969280 - TAIS GRATIERI - null