Study of the effect of Complement System activation in the stability of different compositions of liposomes containning flavonoids: selection of the delivery system more stable and evaluation of its applicability in the therapy of inflammatory diseases.

• Grant number: 06/04398-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2008
• End date: February 28, 2011
• Field of knowledge: Health Sciences - Pharmacy - Medicines Analysis and Control
• Principal Investigator: Yara Maria Lucisano Valim
• Grantee: Ana Paula Landi Librandi
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In inflammatory process, neutrophils have an important participation on the phagocytosis, including the production of reactive species of oxygen and lytic lisosomal enzymes and this process can be stimulated by several ways. However, these reactive species and enzymes present in granules can extravasate to extracellularmedium and lead to injury for host cells as that occur in disease by immunocomplexes. The use of natural compounds with antioxidant actitivity has been very investigated and among them, flavonoids have a special eminence. These activities can be evaluated in vitro employing quimioluminescence assays using luminol and lucigenin as probe. In this way, the aim of the present project is to investigate the in vitro effect of the liposome composition containing flavonoids on the Complement System activation (SC) and in the oxidative metabolism of human neutrophils with the purpose of obtain a delivery system of active substance capable to reach the tissue or cell-target (neutrophils in this case), since the SC has an important role on the process of clearance of liposome and that, in a previous study, the same flavonoids when free showed an inhibitory activity on the production of reactive species of oxygen by rabbit neutrophils in a manner dependent of structure and concentration (MOREIRA, 2004). Moreover, the use of liposomes can overcome the insolubility in water of these compounds and can lead to formulations suitable to in vivo administration and possible therapheutic applications (GONIOTAKI et al, 2004). In addition, since this delivery system has the ability of altering the pharmakinetics, it can eventually reduce the IC50 of flavonoids obtained when free compounds were tested on oxidative metabolism of neutrophils (MOREIRA, 2004).

Scientific publications

(4)

(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)

SANTOS, EVERTON O. L.; KABEYA, LUCIANA M.; FIGUEIREDO-RINHEL, ANDREA S. G.; MARCHI, LARISSA F.; ANDRADE, MICASSIO F.; PIATESI, FABIANA; PAOLIELLO-PASCHOALATO, ADRIANA B.; AZZOLINI, ANA ELISA C. S.; LUCISANO-VALIM, YARA M.. Flavonols modulate the effector functions of healthy individuals' immune complex-stimulated neutrophils: A therapeutic perspective for rheumatoid arthritis. International Immunopharmacology, v. 21, n. 1, p. 102-111, JUL 2014. (07/00161-3, 07/00840-8, 06/04398-5, 07/06925-5, 07/02487-3)

LANDI-LIBRANDI, ANA PAULA; CHRYSOSTOMO, TAIS NADER; CALEIRO SEIXAS AZZOLINI, ANA ELISA; MARZOCCHI-MACHADO, CLENI MARA; DE OLIVEIRA, CARLOS ALBERTO; LUCISANO-VALIM, YARA MARIA. Study of quercetin-loaded liposomes as potential drug carriers: in vitro evaluation of human complement activation. Journal of Liposome Research, v. 22, n. 2, p. 89-99, JUN 2012. (07/00161-3, 06/04398-5)

LANDI-LIBRANDI, ANA PAULA; CALEIRO SEIXAS AZZOLINI, ANA ELISA; DE OLIVEIRA, CARLOS ALBERTO; LUCISANO-VALIM, YARA MARIA. Inhibitory activity of liposomal flavonoids during oxidative metabolism of human neutrophils upon stimulation with immune complexes and phorbol ester. DRUG DELIVERY, v. 19, n. 4, p. 177-187, MAY 2012. (07/00161-3, 06/04398-5)

LANDI-LIBRANDI, ANA PAULA; DE OLIVEIRA, CARLOS ALBERTO; CALEIRO SEIXAS AZZOLINI, ANA ELISA; KABEYA, LUCIANA MARIKO; DEL CIAMPO, JOSE ORESTES; LOPES BADRA BENTLEY, MARIA VITORIA; LUCISANO-VALIM, YARA MARIA. In vitro evaluation of the antioxidant activity of liposomal flavonols by the HRP--H2O2--luminol system. Journal of Microencapsulation, v. 28, n. 4, p. 258-267, 2011. (07/00161-3, 06/04398-5)