Phthalocyanine-loaded nanostructured lipid carriers functionalized with folic acid for photodynamic therapy

Author(s):Show less -

Oshiro-Junior, Joao A. ^[1] ; Sato, Mariana Rillo ^[2] ; Boni, Fernanda Isadora ^[2] ; Macena Santos, Karen Loraine ^[1] ; de Oliveir, Kleber Thiago ^[3] ; de Freitas, Laura Marise ^[4] ; Fontana, Carla Raquel ^[4] ; Nicholas, Dean ^[5] ; McHale, Anthony ^[5] ; Callan, John F. ^[5] ; Chorilli, Marlus ^{[1, 2]}

Affiliation

^[1] State Univ Paraiba UEPB, Ctr Biol & Hlth Sci, Grad Program Pharmaceut Sci, Campina Grande, Paraiba - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Drugs & Med, Rodovia Araraquara Jau, Km 1, Sao Paulo - Brazil

^[3] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil

^[4] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Rodovia Araraquara Jau, Km 1, Sao Paulo - Brazil

^[5] Univ Ulster, Biomed Sci Res Inst, Coleraine, Londonderry - North Ireland

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 108, MAR 2020.
• Web of Science Citations: 0

Abstract

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for > 90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 +/- 0.58% and 27.7 +/- 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 mu M of PS present non-toxic with > 80 +/- 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 +/- 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 18/17573-7 - Potential effect of hypericin-loaded mucoadhesive nanostructured systems associated with antimicrobial photodynamic and sonodynamic therapies against Candida albicans strains
• Grantee: Mariana Rillo Sato
• Support type: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/11198-4 - Nanostructured lipid carriers dispersed in situ gelling hydrogel for vaginal administration of hypericin associated with photodynamic therapy in the treatment of vulvovaginal candidiasis
• Grantee: Mariana Rillo Sato
• Support type: Scholarships in Brazil - Doctorate