Polymeric Nanoparticles of Brazilian Red Propolis Extract: Preparation, Characterization, Antioxidant and Leishmanicidal Activity.
The ever-increasing demand for natural products and biotechnology derived from bees and ultra-modernization of various analytical devices has facilitated the rational and planned development of biotechnology products with a focus on human health to treat chronic and neglected diseases. The aim of the present study was to prepare and characterize polymeric nanoparticles loaded with Brazilian red propolis extract and evaluate the cytotoxic activity of "multiple-constituent extract in co-delivery system" for antileishmanial therapies. The polymeric nanoparticles loaded with red propolis extract were prepared with a combination of poly-ε-caprolactone and pluronic using nanoprecipitation method and characterized by different analytical techniques, antioxidant and leishmanicidal assay. The red propolis nanoparticles in aqueous medium presented particle size (200-280 nm) in nanometric scale and zeta analysis (-20 to -26 mV) revealed stability of the nanoparticles without aggregation phenomenon during 1 month. After freeze-drying method using cryoprotectant (sodium starch glycolate), it was possible to observe particles with smooth and spherical shape and apparent size of 200 to 400 nm. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and thermal analysis revealed the encapsulation of the flavonoids from the red propolis extract into the polymeric matrix. Ultra performance liquid chromatography coupled with diode array detector (UPLC-DAD) identified the flavonoids liquiritigenin, pinobanksin, isoliquiritigenin, formononetin and biochanin A in ethanolic extract of propolis (EEP) and nanoparticles of red propolis extract (NRPE). The efficiency of encapsulation was determinate, and median values (75.0 %) were calculated using UPLC-DAD. 2,2-Diphenyl-1-picryhydrazyl method showed antioxidant activity to EEP and red propolis nanoparticles. Compared to negative control, EEP and NRPE exhibited leishmanicidal activity with an IC50 value of ≅38.0 μg/mL and 31.3 μg/mL, 47.2 μg/mL, 154.2μg/mL and 193.2 μg/mL for NRPE A1, NRPE A2, NRPE A3 and NRPE A4, respectively. Nanoparticles loaded with red propolis extract in co-delivery system and EEP presented cytotoxic activity on Leishmania (V.) braziliensis. Red propolis extract loaded in nanoparticles has shown to be potential candidates as intermediate products for preparation of various pharmaceutical dosage forms containing red propolis extract in the therapy against negligible diseases such as leishmaniasis. Graphical Abstract Some biochemical mechanisms of cellular debridement of Leishmania (V.) braziliensis species by the flavonoids of red propolis extract (EEP) or NRPE loaded with red propolis extract.
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil. ticianogn@yahoo.com.br.
Ticiano Gomes
TG
do Nascimento
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Priscilla Fonseca
PF
da Silva
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Lais Farias
LF
Azevedo
Quality Control of Drugs Laboratory (LCQMed), Postgraduate Program of Pharmaceutical Science, Department of Pharmacy, Federal University of Rio Grande do Norte, Rua General Cordeiro de Farias S/N, Petrópolis, Natal, RN, 59010-180, Brazil.
Louisianny Guerra
LG
da Rocha
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Isabel Cristina Celerino
IC
de Moraes Porto
Quality Control of Drugs Laboratory (LCQMed), Postgraduate Program of Pharmaceutical Science, Department of Pharmacy, Federal University of Rio Grande do Norte, Rua General Cordeiro de Farias S/N, Petrópolis, Natal, RN, 59010-180, Brazil.
Túlio Flávio Accioly
TF
Lima E Moura
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Irinaldo Diniz
ID
Basílio-Júnior
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Luciano Aparecido Meireles
LA
Grillo
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Camila Braga
CB
Dornelas
Quality Control Laboratory of Drugs and Medicines, Postgraduate Program in Pharmaceutical Sciences, School of Nursing and Pharmacy, Federal University of Alagoas, Alagoas, Avenida Lourival Melo Mota, s/n Campus A. C. Simões, University City, Tabuleiro dos Martins, 57072-900, Maceió, Alagoas, Brazil.
Eduardo Jorge da Silva
EJ
Fonseca
Laboratory of Pharmaceutical analysis, Postgraduate Program of Pharmaceutical Science, Pharmacy College, Federal University of Vales do Jequitinhonha e Mucuri, Campus JK, Rodovia MGT 367 Km 583, n° 5000, Alto da Jacuba, Diamantina, Minas Gerais, 39100-000, Brazil.
Eduardo
E
de Jesus Oliveira
Department of Pharmaceutical Science, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK.
Alex Tong
AT
Zhang
Department of Pharmaceutical Science, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK.
David G
DG
Watson
ATR-FTIR; Antioxidant activity; Leishmanicidal activity; PCL-pluronic nanoparticles; Red propolis extract; SEM analysis; Thermal analysis; UPLC-DAD