Nanotech 2010

Topical Delivery System for ZnPcSO4 based on Liquid Crystalline Phases for use in PDT of skin cancer

W.S.G. Medina, F.S.G. Praça, M.V.B.L. Bentley
University Of São Paulo, BR

Keywords: photodynamic therapy, zinc phtalocyanine tetrasulphonet, liquid crystalline phases

Abstract:

Photodynamic therapy (PDT) is an attractive and innovative modality for the treatment of small and superficial tumors. Zinc Phtalocyanine Tetrasulphonet (ZnPcSO4) presents limited penetration into the skin. In this way, lipid absorption enhancers have been proposed as drug delivery systems. Monoolein (MO) is a polar lipid that present absorption enhancer effect and can form lyotropic liquid crystalline phases in the presence of aqueous environment. In this present study we investigated a new potential application of the cubic and lamellar phase (MO/water) for topical delivery of photosensitizer used in PDT of cutaneous diseases. The cubic and lamellar phases were prepared addition of water 30 and 10% respectively. The ZnPcSO4 0,003ug/mg of gel was dissolved in water before mixed with MO. Control formulation hydroxyl ethyl cellulose at 3% w/w was also assayed. Liquid crystalline phases were characterized by optical microscopy in polarized light at 25ºC. The in vitro permeation was measured with a Franz diffusion cell system contained 1.77cm2 diffusion area and 7 mL of isotonic pH 7.2 phosphate buffer as receptor medium. Permeation profiles were constructed by plotting the total amount of fluorimetrically determined ZnPcSO4 transported across the pig ear skin ug/cm2/hours. In vitro and in vivo retention of ZnPcSO4 was measured in pig ear skin and hairless mouse, respectively. The liquid crystalline phases present similar permeation profiles as the control formulation provided higher ZnPcSO4 permeated amounts. The both lamellar and cubic phase showed similar results for in vitro studies, but significantly difference (p<0.001) for in vivo studies. It is possible because higher hydrated skin when on diffusion cell, can transformed the lamellar phase into the cubic phase, but is not occurred in vivo. However, in stratum corneum, cubic and lamellar phases provided at 8 and 12 hours the highest drug retention, when used hydroxyl ethyl cellulose as control formulation. In vitro and in vivo results showed that the presence of cubic and lamellar phase of MO/water increased the ZnPcSO4 skin retention, which can be considered an important advance in the research field of delivery systems for PDT of skin cancer.
 
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