PneumoPhageKill: development of a therapeutic system containing nanoencapsulated strictly lytic bacteriophages for Pseudomonas aeruginosa, for the treatment of bacterial pneumonia via nebulization

• Grant number: 13/03181-6
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2014
• End date: December 31, 2015
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marta Maria Duarte Carvalho Vila
• Grantee: Marta Maria Duarte Carvalho Vila
• Host Institution: Pró-Reitoria Acadêmica. Universidade de Sorocaba (UNISO). Sorocaba , SP, Brazil
• Associated researchers: Marco Vinícius Chaud ; Marli Gerenutti ; Matthieu Tubino ; Vitor Manuel Cardoso Figueiredo Balcão

Abstract

The emergence of bacterial strains resistant to antibiotics and poor penetration of antibiotics in bacterial biofilms puts emphasis on the need for safe and effective alternatives for antimicrobial treatment. The application of strictly lytic bacteriophage (or phage) has been proposed as an alternative (or supplement) to conventional antibiotics, allowing the release of natural predators of bacteria directly at the site of infection. Probably the biggest advantage of phage-based therapies lies in the fact that the phage replicates directly at the site of infection, becoming widely available where they are most needed. When compared to antibiotics, phages have several important advantages: (i) increasing and permanently high concentrations at the site of infection in the presence of (viable) bacteria being disposed just after eradication of the bacterial host, (ii) full compatibility with antibiotics, (iii) specific against target bacteria, (iv) greater penetration of bacterial biofilm, by inducing production of enzymes that hydrolyze the polymeric matrix of the biofilm, and (v) while bacteria may develop resistance to phage, isolation and large scale production of new phages is much more simple and economical than developing new antibiotics. Water in oil in water (W/O/W) multiple emulsions are examples of emulsions where small water droplets are dispersed in larger droplets of oil, which in turn are dispersed in a continuous aqueous phase. Because of their compartimentalized internal structure, multiple emulsions are advantageous for encapsulation compared to simple O/W emulsions, such as the ability to transport both polar and nonpolar molecules, and allow a better control of the release of therapeutic molecules. This research project will investigate the potential of nanoencapsulating a lytic phage (or lytic phage cocktail) with broad-spectrum capable of infecting Pseudomonas aeruginosa. The physico-chemical characterization of the phage encapsulating nanoformulation include the determination of particle size and particle size distribution via analysis of the zeta potential, surface morphology via SEM / TEM, encapsulation efficiency and thermal analysis by DSC. The antimicrobial activity of nanoemulsions with encapsulated phage particles produced will also be tested in vitro. (AU)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RIOS, ALESSANDRA C.; VILA, MARTA M. D. C.; LIMA, RENATA; DEL FIOL, FERNANDO S.; TUBINO, MATTHIEU; TEIXEIRA, JOSE A.; BALCAO, VICTOR M.. Structural and functional stabilization of bacteriophage particles within the aqueous core of a W/O/W multiple emulsion: A potential biotherapeutic system for the inhalational treatment of bacterial pneumonia. Process Biochemistry, v. 64, p. 177-192, JAN 2018. (13/03181-6, 16/08884-3, 16/12234-4)

POLES, JR., ANTONIO A.; BALCAO, VICTOR M.; CHAUD, MARCO V.; VILA, MARTA M. D. C.; ARANHA, NORBERTO; YOSHIDA, VALQUIRIA M. H.; OLIVEIRA, JR., JOSE M.. Study of the elemental composition of saliva of smokers and nonsmokers by X-ray fluorescence. Applied Radiation and Isotopes, v. 118, p. 221-227, DEC 2016. (13/03181-6, 12/15651-4)

JODAR, KARIN S. P.; BALCAO, VICTOR M.; CHAUD, MARCO V.; TUBINO, MATTHIEU; YOSHIDA, VALQUIRIA M. H.; OLIVEIRA, JR., JOSE M.; VILA, MARTA M. D. C.. Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Journal of Pharmaceutical Sciences, v. 104, n. 7, p. 2241-2254, JUL 2015. (14/21122-0, 13/03181-6, 12/15651-4)

BALCAO, VICTOR M.; VILA, MARTA M. D. C.. Structural and functional stabilization of protein entities: state-of-the-art. Advanced Drug Delivery Reviews, v. 93, p. 25-41, OCT 1 2015. (13/03181-6)

FABIANA CRISTINA ROSA MITELMÃO; SALVADOR MANGINI FILHO; MARCO VINÍCIUS CHAUD; MARTA MARIA DUARTE CARVALHO VILA; VICTOR MANUEL CARDOSO FIGUEIREDO BALCÃO; JOSÉ MARTINS DE OLIVEIRA JUNIOR. Caracterização física de Cateteres Centrais de Inserção Periférica (CCIP). MATERIA-RIO DE JANEIRO, v. 25, n. 1, 2020-04-06. (16/08884-3, 18/05522-9, 13/03181-6, 12/15651-4)

BALCAO, VICTOR M.; GLASSER, CASSIA A.; CHAUD, MARCO V.; DEL FIOL, FERNANDO S.; TUBINO, MATTHIEU; VILA, MARTA M. D. C.. Biomimetic aqueous-core lipid nanoballoons integrating a multiple emulsion formulation: A suitable housing system for viable lytic bacteriophages. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 123, p. 478-485, NOV 1 2014. (13/03181-6)

RIOS, ALESSANDRA C.; MOUTINHO, CARLA G.; PINTO, FLAVIO C.; DEL FIOL, FERNANDO S.; JOZALA, ANGELA; CHAUD, MARCO V.; VILA, MARTA M. D. C.; TEIXEIRA, JOSE A.; BALCAO, VICTOR M.. Alternatives to overcoming bacterial resistances: State-of-the-art. MICROBIOLOGICAL RESEARCH, v. 191, p. 51-80, 2016. (13/03181-6)

REBELO, MARCIA A.; ALVES, THAIS F. R.; DE LIMA, RENATA; OLIVEIRA, JR., JOSE M.; VILA, MARTA M. D. C.; BALCAO, VICTOR M.; SEVERINO, PATRICIA; CHAUD, MARCO V.. Scaffolds and tissue regeneration: An overview of the functional properties of selected organic tissues. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v. 104, n. 7, p. 1483-1494, OCT 2016. (13/03181-6, 13/19300-4)