Glycerol monolaurate nanocapsules for biomedical applications: in vitro toxicological studies
- 91 Downloads
The glycerol monolaurate (GML) is a surfactant used in the food industry and has potent antimicrobial activity against many microorganisms; however, the use of GML is not expanded due its high melting point and poor solubility in water. The aim of the study was to produce, characterize, and evaluate in vitro the cytotoxicity of GML and GML nanocapsules. The GML nanocapsules were produced and characterized by a mean diameter, zeta potential, and polydispersity index. The cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, thiobarbituric acid reactive substances (TBARS), and hemolytic activity. The genotoxicity was verified by comet assay. The physicochemical parameters showed a mean diameter of 192.5 ± 2.8 nm, a polydispersity index of 0.061 ± 0.018, and a zeta potential about − 21.9 ± 1 mV. The viability test demonstrated the protector effect of GML nanocapsule compared with the GML on peripheral blood mononuclear cells (PBMC) and VERO cells (isolated from kidney epithelial cells extracted from an African green monkey). A reduction in lipid peroxidation and lactate dehydrogenase release in GML nanocapsule–exposed cells compared with GML treated cells was observed. The damage on erythrocytes was addressed in treatment with GML, while the treatment with GML nanocapsules did not cause an effect. Moreover, the comet assay showed that the GML-caused genotoxicity and GML nanocapsules do not demonstrate damage. The study showed the reduction of toxicity of GML nanocapsules by many methods used in antimicrobial therapy.
KeywordsNanocapsules Hemolytic activity VERO cells Lipid peroxidation
LQSL produced and characterized the nanocapsules. PSBO, WPSF, RAV, JLG, and MRS conducted the cytotoxicity and genotoxicity experiments. All authors read and approved the manuscript.
This work received financial support from PPGPE/Universidade Franciscana-Probic, CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) (Finance Code 001), and FAPERGS (Fundação de Amparo a Pesquisa do Rio Grande do Sul).
Compliance with ethical standards
The study was approved by the Research Ethics Committee of the Human of Universidade Franciscana (CAAE: 31211214.4.0000.5306).
Conflict of interest
The authors declare that they have no conflict of interest.
- Agulla J, Brea D, Argibay B, Novo M, Campos F, Sobrino T, Blanco M, Castillo J, Ramos-Cabrer P (2014) Quick adjustment of imaging tracer payload, for in vivo applications of theranostic nanostructures in the brain. Nanomedicine 10:851–858. https://doi.org/10.1016/j.nano.2013.12.004 CrossRefPubMedGoogle Scholar
- Anang DM, Rusul G, Bakar J, Ling FH (2007) Effects of lactic acid and lauricidin on the survival of Listeria monocytogenes, Salmonella enteritidis and Escherichia coli O157:H7 in chicken breast stored at 4 °C. Food Control 18:961–969. https://doi.org/10.1016/j.foodcont.2006.05.015 CrossRefGoogle Scholar
- Arunkumar P, Raju B, Vasantharaja R, Vijayaraghavan S, Preetham Kumar B, Jeganathan K, Premkumar K (2015) Near infra-red laser mediated photothermal and antitumor efficacy of doxorubicin conjugated gold nanorods with reduced cardiotoxicity in swiss albino mice. Nanomedicine 11:1435–1444. https://doi.org/10.1016/j.nano.2015.03.012 CrossRefPubMedGoogle Scholar
- Bergsson G, Arnfinnsson J, Steingrímsson O, Thormar H (2001) Killing of Gram-positive cocci by fatty acids and monoglycerides. APMIS 109:670–678. https://doi.org/10.1034/j.1600-0463.2001.d01-131.x CrossRefPubMedGoogle Scholar
- Bouchemal K, Briançon S, Perrier E, Fessi H, Bonnet I, Zydowicz N (2004) Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification. Int J Pharm 269:89–100. https://doi.org/10.1016/j.ijpharm.2003.09.025 CrossRefPubMedGoogle Scholar
- Carrera-Rotllan J, Estrada-Garcia L (1998) Age-dependent changes and interrelations of number of cells and biochemical parameters (glucose, triglycerides, TBARS, calcium, phosphorus) in cultured human vein endothelial cells. Mech Ageing Dev 103:13–26. https://doi.org/10.1016/S0047-6374(98)00007-4 CrossRefPubMedGoogle Scholar
- Choi CW, Kim SC, Hwang SS, Choi BK, Ahn HJ, Lee MY, Park SH, Kim SK (2002) Antioxidant activity and free radical scavenging capacity between Korean medicinal plants and flavonoids by assay-guided comparison. Plant Sci 163:1161–1168. https://doi.org/10.1016/S0168-9452(02)00332-1 CrossRefGoogle Scholar
- Costa F, Dornelles E, Mânica-Cattani MF, et al (2012) Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene citrate in oxidative metabolism. Reprod Biomed Online 24:474–481. https://doi.org/10.1016/j.rbmo.2012.01.009
- Gali Y, Delezay O, Brouwers J, Addad N, Augustijns P, Bourlet T, Hamzeh-Cognasse H, Arien KK, Pozzetto B, Vanham G (2010) In vitro evaluation of viability, integrity, and inflammation in genital epithelia upon exposure to pharmaceutical excipients and candidate microbicides. Antimicrob Agents Chemother 54:5105–5114. https://doi.org/10.1128/AAC.00456-10 CrossRefPubMedPubMedCentralGoogle Scholar
- García O, Mandina T, Lamadrid AI, Diaz A, Remigio A, Gonzalez Y, Piloto J, Gonzalez JE, Alvarez A (2004) Sensitivity and variability of visual scoring in the comet assay: results of an inter-laboratory scoring exercise with the use of silver staining. Mutat Res Fundam Mol Mech Mutagen 556:25–34. https://doi.org/10.1016/j.mrfmmm.2004.06.035 CrossRefGoogle Scholar
- Inácio ÂS, Mesquita KA, Baptista M, Ramalho-Santos J, Vaz WLC, Vieira OV (2011) In vitro surfactant structure-toxicity relationships: implications for surfactant use in sexually transmitted infection prophylaxis and contraception. PLoS One 6:e19850. https://doi.org/10.1371/journal.pone.0019850 CrossRefPubMedPubMedCentralGoogle Scholar
- Lopes LQS, Santos CG, de Almeida Vaucher R, Gende L, Raffin RP, Santos RCV (2016a) Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees. Microb Pathog 97:183–188. https://doi.org/10.1016/j.micpath.2016.05.014 CrossRefPubMedGoogle Scholar
- Mann T (2006) Coconut oil – ideal fat next only to mother’s milk (scanning coconut’s horoscope). Clin Med (Northfield Il) 7:16–19Google Scholar
- Nguyen TDT, Pitchaimani A, Aryal S (2016) Engineered nanomedicine with alendronic acid corona improves targeting to osteosarcoma. Sci Rep 6. https://doi.org/10.1038/srep36707
- Noll KS, Prichard MN, Khaykin A et al (2012) The natural antimicrobial peptide subtilosin acts synergistically with glycerol monolaurate, lauric arginate, and ε-poly-L-lysine against bacterial vaginosis-associated pathogens but not human lactobacilli. Antimicrob Agents Chemother 56:1756–1761. https://doi.org/10.1128/AAC.05861-11 CrossRefPubMedGoogle Scholar
- Panyuta O, Belava V, Fomaidi S, Kalinichenko O, Volkogon M, Taran N (2016) The effect of pre-sowing seed treatment with metal nanoparticles on the formation of the defensive reaction of wheat seedlings infected with the eyespot causal agent. Nanoscale Res Lett 11:92. https://doi.org/10.1186/s11671-016-1305-0 CrossRefPubMedPubMedCentralGoogle Scholar
- Pool H, Quintanar D, Figueroa J de D et al (2012) Polymeric nanoparticles as oral delivery systems for encapsulation and release of polyphenolic compounds: impact on quercetin antioxidant activity & bioaccessibility. Food Biophys 7:276–288. https://doi.org/10.1007/s11483-012-9266-z CrossRefGoogle Scholar
- Projan SJ, Brown-Skrobot S, Schlievert PM, Vandenesch F, Novick RP (1994) Glycerol monolaurate inhibits the production of β-lactamase, toxic shock syndrome toxin-1, and other staphylococcal exoproteins by interfering with signal transduction. J Bacteriol 176:4204–4209CrossRefPubMedPubMedCentralGoogle Scholar
- Raffin RP, Obach ES, Mezzalira G et al (2003) Nanocápsulas poliméricas secas contendo indometacina: Estudo de formulação e de tolerância gastrintestinal em ratos. Acta Farm Bonaer 22:163–172Google Scholar
- Ritschel WA (1996) Microemulsion technology in the reformulation of cyclosporine: the reason behind the pharmacokinetic properties of Neoral. Clin Transpl 10:364–373Google Scholar
- Souza JLS, da Silva AF, Carvalho PHA, Pacheco BS, Pereira CMP, Lund RG (2014) Aliphatic fatty acids and esters: inhibition of growth and exoenzyme production of Candida, and their cytotoxicity in vitro: anti-Candida effect and cytotoxicity of fatty acids and esters. Arch Oral Biol 59:880–886. https://doi.org/10.1016/j.archoralbio.2014.05.017 CrossRefPubMedGoogle Scholar
- Tangwatcharin P, Khopaibool P (2012) Inhibitory effects of the combined application of lauric acid and monolaurin with lactic acid against Staphylococcus aureus in pork. ScienceAsia 38:54–63. https://doi.org/10.2306/scienceasia1513-1874.2012.38.054 CrossRefGoogle Scholar