Abstract
Since violacein—an antibiotic, antiviral, and antiparasitic compound—exhibits poor solubility in water, polymeric poly-(d,l-lactide-co-glycolide) nanoparticles containing this compound improved its solubility and biological activity. The nanoparticles were prepared by the nanoprecipitation method and characterized in terms of average diameter, zeta potential, drug loading, polymer recovery, in vitro release kinetic, and in vitro antibacterial activity. Nanoparticles with diameters between 116 and 139 nm and negative-charged outer surfaces were obtained. Drug-loading efficiency and polymer recovery were 87 and 93%, respectively. In vitro release kinetics assays showed that violacein loaded in these nanoparticles has sustained release behavior until 5 days. Both free and nanoparticles-loaded violacein exhibited in vitro antibacterial activity against Staphylococcus aureus ATCC 29213 and ATCC 25923 strains and exhibiting around two to five times lower minimum inhibitory concentration (MIC) than free violacein, respectively. The encapsulated violacein was efficient against methicilin-resistant Staphylococcus aureus (MRSA) strains. No significant activity against Escherichia coli and Salmonella enterica was found.
Similar content being viewed by others
References
Bromberg N, Justo GZ, Haun M, Durán N, Ferreira CV (2005) Violacein cytotoxicity on human blood lymphocytes and effect on phosphatases. J Enzym Inhib Med Chem 20:449–454
Bromberg N, Dreyfuss JL, Regatieri CV, Palladino MV, Durán N, Nader HB, Haun M, Justo GZ (2010) Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor. Chem Biol Interact 186:43–52
CLSI—Committee for Clinical Laboratory Standards (2003) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 6th edn. CLSI, Wayne, USA
Cui F, Shi K, Zhang L, Tao A, Kawashima Y (2006) Biodegradable nanoparticles loaded with insulin-phospholipid complex for oral delivery: preparation, in vitro characterization and in vivo evaluation. J Control Release 114:242–250
Cury GG, Mobilon C, Stehling EG, Lancellotti M, Ramos MC, Martinez R, Brocchi M, Silveira WD (2009) Molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated in two metropolitan areas of São Paulo State, Southeast Brazil. Braz J Infect Dis 13:165–169
De Carvalho DD, Costa FT, Duran N, Haun M (2006) Cytotoxic activity of violacein in human colon cancer cells. Toxicol In Vitro 20:1514–1521
De Souza AO, Aily DCG, Sato DN, Durán N (1999) Atividade da violaceina in vitro sobre o Mycobacterium tuberculosis H37RA. Rev Inst Adolfo Lutz 58:59–62
Demling RH, Waterhouse B (2007) The increasing problem of wound bacterial burden and infection in acute and chronic soft-tissue wounds caused by methicillin-resistant Staphylococcus aureus. J Burns Wounds 7:89–98
Durán N, Menck CF (2001) Chromobacterium violaceum: a review of pharmacological and industrial perspectives. Crit Rev Microbiol 27:201–222
Durán N, Justo GZ, Melo PS, De Azevedo MBM, Brito ARMMS, Almeida ABA, Haun M (2003) Evaluation of the antiulcerogenic activity of violacein and its modulation by the inclusion complexation with beta-cyclodextrin. Can J Physiol Pharmacol 81:387–396
Durán N, Justo GZ, Ferreira CV, Melo PS, Cordi L, Martins D (2007a) Violacein: properties and biological activities. Biotechnol Appl Biochem 48:127–133
Durán N, Marcato PD, De Souza GD, Alves OL, Esposito E (2007b) Antibacterial effect of silver nanoparticles produced by fungal process on textile fabrics and their effluent treatment. J Biomed Nanotechnol 3:203–208
Durán N, Marcato PD, Buffo CMS, De Azevedo MMM, Esposito E (2007c) Poly (epsilon-caprolactone)/propolis extract: microencapsulation and antibacterial activity evaluation. Pharmazie 62:287–290
Durán N, Alvarenga MA, Da Silva EC, Melo PS, Marcato PD (2008) Microencapsulation of antibiotic rifampicin in poly(3-hydroxybutyrate-co-3-hydroxyvalerate). Arch Pharmacal Res 31:1509–1516
Ferreira CV, Bos CL, Versteeg HH, Justo GZ, Durán N, Peppelenbosch MP (2004) Molecular mechanism of violacein-mediated human leukemia cell death. Blood 104:1459–1464
Gimenez IF, Anazetti MC, Melo PS, Haun M, De Azevedo MMM, Durán N, Alves OL (2005) Cytotoxicity on V79 and HL60 cell lines by thiolated-β-cyclodextrin-Au/violacein nanoparticles. J Biomed Nanotechnol 1:352–358
Har-el YE, Kato Y (2007) Intracellular delivery of nanocarriers for cancer therapy. Curr Nanosci 3:329–338
Jain KK (2008) Recent advances in nanooncology. Technol Cancer Res Treat 7:1–13
Kodach LL, Bos CL, Durán N, Peppelenbosch MP, Ferreira CV, Hardwick JC (2006) Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells. Carcinogenesis 27:508–516
Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, Cui L, Oguchi A, Aoki K, Nagai Y, Lian J, Ito T, Kanamori M, Matsumaru H, Maruyama A, Murakami H, Hosoyama A, Mizutani-Ui Y, Takahashi NK, Sawano T, Inoue R, Kaito C, Sekimizu K, Hirakawa H, Kuhara S, Goto S, Yabuzaki J, Kanehisa M, Yamashita A, Oshima K, Furuya K, Yoshino C, Shiba T, Hattori M, Ogasawara N, Hayashi H, Hiramatsu K (2001) Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet 357(9264):1225–1240
Lopes SCP, Yara C, Justo GZ, Nogueira PA, Rodrigues FLS, Goelnitz U, Wunderlich G, Facchini G, Brocchi M, Durán N, Costa FTM (2009) Violacein extracted from Chromobacterium violaceum inhibits Plasmodium growth in vitro and in vivo. Antimicrob Agents Chemother 53:2149–2152
Marcato PD, Durán N (2008) New aspects of nanopharmaceutical delivery systems. J Nanosci Nanotechnol 8:2216–2229
McClelland M, Sanderson KE, Spieth J, Clifton SW, Latreille P, Courtney L, Porwollik S, Ali J, Dante M, Du F, Hou S, Layman D, Leonard S, Nguyen C, Scott K, Holmes A, Grewal N, Mulvaney E, Ryan E, Sun H, Florea L, Miller W, Stoneking T, Nhan M, Waterston R, Wilson RK (2001) Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413(6858):852–856
Melo PS, De Azevedo MMM, Frungillo L, Anazetti MC, Marcato PD, Marcato PD, Durán N (2009) Nanocytotoxicity: violacein and violacein-loaded poly(d,l-lactide-co-glycolide) nanoparticles acting on human leukemic cells. J Biomed Nanotechnol 5:192–201
Mosqueira VC, Legrand P, Pinto-Alphandary H, Puisieux F, Barratt G (2000) Poly(d, l-lactide) nanocapsules prepared by a solvent displacement process: influence of the composition on physicochemical and structural properties. J Pharm Sci 89:614–626
Murray CK (2008) Infectious disease complications of combat-related injuries. Crit Care Med 36:S358–S364
Nair LS, Laurencin CT (2007) Biodegradable polymers as biomaterials. Prog Polym Sci 32:762–798
Powell JP, Wenzel RP (2008) Antibiotic options for treating community-acquired MRSA. Expert Rev Anti Infect Ther 6:299–307
Rettori D, Durán N (1998) Production, extraction and purification of violacein: an antibiotic pigment produced by Chromobacterium violaceum. World J Microbiol Biotechnol 14:685–688
Schaffazick SR, Guterres SSU, Freitas LD, Polhmann AR (2003) Physicochemical characterization and stability of the polymeric nanoparticle systems for drug administration. Quimica Nova 26:726–737
Sievert DM, Rudrik JT, Patel JB, McDonald LC, Wilkins MJ, Hageman JC (2008) Vancomycin-resistant Staphylococcus aureus in the United States 2002–2006. Clin Infect Dis 46:668–674
Soares MJ, Teixeira LA, Nunes MR, da Silva Carvalho MC, Ferreira-Carvalho BT, Figueiredo AM (2001) Analysis of different molecular methods for typing methicillin-resistant Staphylococcus aureus isolates belonging to the Brazilian epidemic clone. J Med Microbiol 50:732–742
WHO—World Health Organization (2008) available at www.who.org. Accessed 23 Aug 2008
Zhang YQ, Ren SX, Li HL, Wang YX, Fu G, Yang J, Qin ZQ, Miao YG, Wang WY, Chen RS, Shen Y, Chen Z, Yuan ZH, Zhao GP, Qu D, Danchin A, Wen YM (2003) Genome-based analysis of virulence genes in a non-biofilm-forming Staphylococcus epidermidis strain (ATCC 12228). Mol Microbiol 49:1577–1593
Acknowledgments
This study was supported by FAPESP, CNPq, MCT/PADCT/IMMP, and the Brazilian Nanobiotechnology Network (CNPq/MCT). Dorival Martins held a fellowship from FAPESP, project number 06/58826-8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Martins, D., Costa, F.T.M., Brocchi, M. et al. Evaluation of the antibacterial activity of poly-(d,l-lactide-co-glycolide) nanoparticles containing violacein. J Nanopart Res 13, 355–363 (2011). https://doi.org/10.1007/s11051-010-0037-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-010-0037-9