Development and characterization of an amphotericin B - loaded nanoemulsion applied to Candida auris biofilms control

Author(s)

Marena, Gabriel Davi ; dos Santos Ramos, Matheus Aparecido ; Carvalho, Gabriela Correa ; de Lima, Laura Caminitti ; Carneiro Soares do Nascimento, Andre Luiz ; Sabio, Rafael Miguel ; Rodero, Camila Fernanda ; Sposito, Larissa ; Bauab, Tais Maria ; Chorilli, Marlus

• Document type: Journal article
• Source: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY; v. 74, p. 14-pg., 2022-07-20.

Abstract

Nanoemulsions (NE) belong to the class of emulsions widely used in the scientific field in order to improve drugs bioavailability and selectivity, especially in the control of microbial resistance. Among the resistant microorganisms, Candida auris is highly resistant to conventional treatments and has caused serious public health concerns. The amphotericin B (AmB) has shown good antifungal activity, however, with a considerable level of toxicity. In light of this, the incorporation of AmB in NE comprises an efficient strategy to overcome side effects besides enhancing its action. Furthermore, NE can be lower cost and less complex to develop compared to other systems already available. This work aimed to design, characterize and evaluate AmB-loaded NE (denominated NEA) against C. auris biofilm. NE were prepared by a mixture of phosphate buffered saline (PBS - aqueous phase), cholesterol and sunflower oil (oil phase) and Polyoxyethylene (20) cetyl ether (Brij (R) 58) and soy phosphatidylcholine (surfactants). The proposed nanosystem was successfully characterized and the encapsulation efficiency (EE) and release assays were evaluated using HPLC. NEA was applied against developing and mature biofilms formed by C. auris CDC B11903. The characterization assays results showed a clear liquid NE with the size ranging from 44 to 47 nm, good uniformity and zeta potential (ZP) ranging from -3.77 to -3.56 mV. The thermal data analysis confirmed that the drug incorporation did not change the NE profile. Cryo-TEM images exhibited spherical shape with nanostructures well dispersed with an average size of 40 nm. NEA EE ranged from 69 to 17%, having a slower release potential compared to free AmB. In vitro studies performed against C. auris biofilms displayed promising results with high antibiofilm capacity regarding to the growth control (with no treatment). Considering the aforementioned, NE displayed essential characteristics for an effective nanocarrier, exhibiting good EE, slow AmB release and activity against C. auris biofilms. (AU)

• FAPESP's process: 19/26821-7 - Nano-in-nano containing curcumin and benzydamine hydrochloride for the treatment of Vulvovaginal Candidiasis: from development to biological application in vitro and in vivo
• Grantee: Gabriela Corrêa Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/25377-3 - Potential evaluation of cetuximab-modified mesoporous silica nanoparticles as docetaxel carrier to prostate cancer treatment.
• Grantee: Rafael Miguel Sábio
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/09597-6 - Gastroretentive microparticles containing trans resveratrol nanoparticles applied to the treatment of Helicobacter pylori infections
• Grantee: Larissa Sposito
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/09831-9 - Nanoemulsion for co-encapsulation on amphotericin B and micafungin: development and characterizations of the in vitro and in vivo Candida auris potential.
• Grantee: Gabriel Davi Marena
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/23442-2 - Evaluation of the potential of liposomes for co-encapsulation of amphotericin B and micafungin in the treatment of systemic infection caused by Candida auris
• Grantee: Matheus Aparecido dos Santos Ramos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/22758-3 - Evaluation of the nanostructured lipid carriers potential functionalized with folic acid incorporated with rapamycin for breast cancer treatment
• Grantee: Camila Fernanda Rodero
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/23357-5 - Multidrug co-crystals of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Proton Pump Inhibitors (PPIs): development, characterization and biological evaluation in vitro and in vivo
• Grantee: André Luiz Carneiro Soares do Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral