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Lipid-based nanocarriers for Rose Bengal dermal delivery: a promising approach in melanoma treatment
* 1 , 2 , 2 , 2 , 2
1  PhD program in Chemical Science and Technology, Department of Chemistry and Pharmacy, University of Sassari, Italy
2  Department of Chemistry and Pharmacy, University of Sassari, Italy

Abstract:

Rose Bengal (RB) is a photosensitizer dye used for eradicating cancer and microbial cells. Intralesional 10% RB (PV-10®) demonstrated to kill locoregional and metastatic melanoma, in the absence of light, by direct tumor ablation and indirect tumor death thanks to a specific immune response [1]. Nevertheless, RB is only employed in ophthalmic diagnostic because the biopharmaceutical profile limits its therapeutic use [2,3]. Since formulating RB delivery systems has proven to overcome its limits [4], this work focuses on the development of RB lipid-based nanocarriers to treat melanoma via topical application in the absence of light. Solid lipid nanoparticles (SLNs), obtained by solvent emulsification-evaporation, and transfersomes (TFs) obtained by modified reverse evaporation (REV), were prepared both blank and RB-loaded. Dimensional properties, physical stability and the interaction between RB and lipids were evaluated. For blank SLNs, 90 s of sonication at 70% US amplitude allowed to obtain a homogenous polydispersity index (PI=0.225) and stable formulation without phase separation or aggregation. About blank TFs, we obtained the best dimensional stability by REV technique: after three months, size increased from 244 nm to 497.35 nm while TFs prepared by another technique increased from 236.23 nm to 747.4 nm. Moreover, leader TFs were prepared employing ethanol instead of an initial toxic solvent mixture obtaining a safe and more homogeneous system (PI=0,166 vs PI=0.43). Dimensional studies on loaded nanosystems revealed SLNs were 130 nm-sized and TFs 230 nm, both were homogeneous (PI<0.25) and stable after one month. UV-spectrophotometer analysis showed RB maximum absorption wavelength shifted from 549 nm in water to 562 nm when it is formulated in carriers indicating an association with the lipid phase [5]. Cytotoxicity studies on melanoma cells are ongoing; further characterizations and permeation studies are planned. We obtained two stable RB formulations potentially active in eradicating melanoma via dermal delivery.

  1. Liu, H.; Innamarato, P.P.; Kodumudi, K.; Weber, A.; Nemoto, S.; Robinson, J.L.; Crago, G.; McCardle, T.; Royster, E.; Sarnaik, A.A.; et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 2016, 7, 37893–37905, doi:10.18632/oncotarget.9247.
  2. Klaassen, C.D. Pharmacokinetics of rose bengal in the rat, rabbit, dog, and guinea pig. Toxicol. Appl. Pharmacol.1976, 38, 85–100.
  3. Pellosi, D.S.; Estevão, B.M.; Semensato, J.; Severino, D.; Baptista, M.S.; Politi, M.J.; Hioka, N.; Caetano, W. Photophysical properties and interactions of xanthene dyes in aqueous micelles. J. Photochem. Photobiol. Chem.2012, 247, 8–15, doi:10.1016/j.jphotochem.2012.07.009.
  4. Loya-Castro, M.F.; Sánchez-Mejía, M.; Sánchez-Ramírez, D.R.; Domínguez-Ríos, R.; Escareño, N.; Oceguera-Basurto, P.E.; Figueroa-Ochoa, É.B.; Quintero, A.; del Toro-Arreola, A.; Topete, A.; et al. Preparation of PLGA/Rose Bengal colloidal particles by double emulsion and layer-by-layer for breast cancer treatment. J. Colloid Interface Sci.2018, 518, 122–129, doi:10.1016/j.jcis.2018.02.013.
  5. Hugo, E.; Abuin, E.; Lissi, E.; Alarcón, E.; Edwards, A.M. Effect of temperature on the photobehavior of Rose Bengal associated with dipalmitoylphosphatidyl choline liposomes. J. Lumin. 2011, 131, 2468–2472, doi:10.1016/j.jlumin.2011.06.021.

Keywords: Rose Bengal; melanoma; lipid nanocarriers; dermal delivery
Comments on this paper
Fátima García-Villén
Problem PDF
I cannot open the PDF of the present paper, could it be any problem with the file?
Sara Demartis
There shouldn't be any problems but I can send you by email!

Alejandra Martínez-Labrador
stability results
Very interesting article. Congratulations.

I'm curious about the results of stability of 200-RBTF2. Have you got the results until 30 days? And if the answer is yes, what did you find?

Thank you
Sara Demartis
Dear Alejandra,

thank you for your comment. We found that also TF-RB 200 is stable after 30 days since both PI and size did not significantly change. If you have any other curiosity please don't hesitate to ask.

Sara Demartis



 
 
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