Chlorogenic acid nanoemulsion for Staphylococcus aureus causing skin infection: Synthesis, characterization and evaluation of antibacterial efficacy

Year 2023, Volume: 41 Issue: 2, 322 - 330, 30.04.2023

Bahar Gok Yasemin Budama-kilinc

Abstract

Staphylococcus aureus (S. aureus) causes many skin infections such as impetigo, infected abra-sions, cellulitis, folliculitis, subcutaneous abscesses, infected ulcers and sores. In this study, it was aimed to develop a nanoformulation of chlorogenic acid that was efficient against S. aureus. In this context, ultrasonic emulsification method was used for production of the chlo-rogenic acid (CA) nanoemulsion formulation and was characterized in detail. In addition, the kinetic and thermodynamic stability of the CA nanoemulsion formulation was examined. Finally, the broth microdilution method was used to determine the antibacterial activity of the formulation. It was determined that the average droplet size of the CA nanoemulsion for-mulation was 120.4 ± 6.39 nm, the polydispersity index (PdI) was 0.180 ± 0.018, and the zeta potential value was -11.5± 1.15 mV. As a result of the thermodynamic stress tests of the CA na-noemulsion formulation, it was observed that there was no precipitation or phase separation. Moreover, in vitro release study showed a CA release of 75.49% after 48 hours. The antibac-terial results revealed that the CA nanoemulsion formulation was efficient (95% inhibition) against S. aureus (ATCC 25923). As a result, it is thought that CA nanoemulsion is an effective, nano sized and controlled release system based formulation candidate that may be used in the topical treatment of S. aureus causing skin infection.

Keywords

Nanoemulsion, Skin Infection, Chlorogenic Acid, Staphylococcus Aureus

References

• REFERENCES
• [1] Dréno B, Araviiskaia E, Berardesca E, Gontijo G, Sanchez Viera M, Xiang L, et al. Microbiome in healthy skin, update for dermatologists. J Eur Acad Dermatol Venereol 2016;30:2038−2047. [CrossRef]
• [2] Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB, et al. Methicillin-resistant S. aureus infections among patients in the emergency department. N Eng J Med 2006;355:666−674. [CrossRef]
• [3] McCaig LF, McDonald LC, Mandal S, Jernigan DB. Staphylococcus aureus-associated skin and soft tis-sue infections in ambulatory care. Emerg Infect Dis 2006;12:1715. [CrossRef]
• [4] Diaz JH, Lopez FA. Skin soft tissue and systemic bacterial infections following aquatic injuries and exposures. Am J Med Sci 2015;349:269−275. [CrossRef]
• [5] Robbins JR, Bakardjiev AI. Pathogens and the placental fortress. Curr Opin Microbiol 2012;15:36−43. [CrossRef]
• [6] Lowy FD. Staphylococcus aureus infections. N Eng J Med 1998;339:520−532. [CrossRef]
• [7] Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, et al. Novel antibody-antibiotic con-jugate eliminates intracellular S. aureus. Nature 2015;527:323−328. [CrossRef]
• [8] Dhanalakshmi V, Nimal T, Sabitha M, Biswas R, Jayakumar R. Skin and muscle permeating anti-bacterial nanoparticles for treating Staphylococcus aureus infected wounds. J Biomed Mater Res Part B 2016;104:797−807. [CrossRef]
• [9] Sully EK, Geller BL. Antisense antimicrobial thera-peutics. Curr Opin Microbiol 2016;33:47−55. [CrossRef]
• [10] Wang F, Fang RH, Luk BT, Hu CMJ, Thamphiwatana S, Dehaini D, et al. Nanoparticle‐Based antivirulence vaccine for the management of methicillin‐resistant Staphylococcus aureus Skin Infection. Adv Funct Mater 2016;26:1628−1635. [CrossRef]
• [11] Nannini E, Murray BE, Arias CA. Resistance or decreased susceptibility to glycopeptides, dap-tomycin, and linezolid in methicillin-resistant Staphylococcus aureus. Curr Opin Pharmacol 2010;10:516−521. [CrossRef]
• [12] Song M, Zeng Q, Xiang Y, Gao L, Huang J, Huang J, et al. The antibacterial effect of topical ozone on the treatment of MRSA skin infection. Mol Med Rep 2018;17:2449−2455. [CrossRef]
• [13] Hanson B, Dressler A, Harper A, Scheibel R, Wardyn S, Roberts L, et al. Prevalence of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) on retail meat in Iowa. J Infect Public Health 2011;4:169−174. [CrossRef]
• [14] Morehead MS, Scarbrough C. Emergence of global antibiotic resistance. Prim Care 2018;45:467−484.[CrossRef]
• [15] Girish VM, Liang H, Aguilan JT, Nosanchuk JD, Friedman JM, Nacharaju P. Anti-biofilm activity of garlic extract loaded nanoparticles. Nanomed: Nanotechnol Biol Med 2019;20:102009. [CrossRef]
• [16] Rajendran R, Radhai R, Kotresh T, Csiszar E. Development of antimicrobial cotton fabrics using herb loaded nanoparticles. Carbohydrate Polym 2013;91:613−617. [CrossRef]
• [17] Almasi H, Azizi S, Amjadi S. Development and characterization of pectin films activated by nanoemulsion and Pickering emulsion stabilized marjoram (Origanum majorana L.) essential oil. Food Hydrocolloids 2020;99:105338. [CrossRef]
• [18] Harrison JJ, Turner RJ, Joo DA, Stan MA, Chan CS, Allan ND, et al. Copper and quaternary ammonium cations exert synergistic bactericidal and antibiofilm activity against Pseudomonas aeruginosa. Antimicrobial Agents Chemother 2008;52:2870−2881. [CrossRef]
• [19] Karunanidhi A, Thomas R, Van Belkum A, Neela V. In vitro antibacterial and antibiofilm activi-ties of chlorogenic acid against clinical isolates of Stenotrophomonas maltophilia including the tri- methoprim/sulfamethoxazole resistant strain. Bio Med Res Int 2013;2013:392058. [CrossRef]
• [20] Lou Z, Wang H, Zhu, S, Ma C, Wang Z. Antibacterial activity and mechanism of action of chlorogenic acid. J Food Sci 2011;76:M398−M403. [CrossRef]
• [21] Ayaz FA, Hayırlıoglu-Ayaz S, Alpay-Karaoglu S, Grúz J, Valentová K, Ulrichová J, et al. Phenolic acid contents of kale (Brassica oleraceae L. var. acephala DC.) extracts and their antioxidant and antibacterial activities. Food Chem 2008;107:19-−25. [CrossRef]
• [22] Fattouch S, Caboni P, Coroneo V, Tuberoso CI, Angioni A, Dessi S, et al. Antimicrobial activity of Tunisian quince (Cydonia oblonga Miller) pulp and peel polyphenolic extracts. J Agricultural Food Chem 2007;55:963−969. [CrossRef]
• [23] Li G, Wang X, Xu Y, Zhang B, Xia X. Antimicrobial effect and mode of action of chlorogenic acid on Staphylococcus aureus. Eur Food Res Technol 2014;238:589−596. [CrossRef]
• [24] Hussain A, Altamimi MA, Alshehri S, Imam SS, Shakeel F, Singh SK. Novel approach for transdermal delivery of rifampicin to induce synergistic antimy- cobacterial effects against cutaneous and systemic tuberculosis using a cationic nanoemulsion gel. Int J Nanomed 2020;15:1073. [CrossRef]
• [25] Caon T, Campos CEM, Simões CMO, Silva MAS. Novel perspectives in the tuberculosis treatment: Administration of isoniazid through the skin. Int J Pharm 2015;494:463−470. [CrossRef]
• [26] Chen S, Han Y, Yu D, Huo F, Wang F, Li Y, et al. Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis. Drug Deliv 2017;24:467−470. [CrossRef]
• [27] Hamouda T, Baker Jr J. Antimicrobial mecha-nism of action of surfactant lipid preparations in enteric Gram‐negative bacilli. J Appl Microbiol 2000;89:397−403. [CrossRef]
• [28] My A, Vanhecke T, Landers JJ, Hamouda T, Baker JR. The fungicidal activity of novel nanoemulsion (X8W 60 PC) against clinically important yeast and fila-mentous fungi. Mycopathologia 2003;155:195−201.[CrossRef]
• [29] Pannu J, McCarthy A, Martin A, Hamouda T, Ciotti S, Ma L, et al. In vitro antibacterial activity of NB-003 against Propionibacterium acnes. Antimicrobial Agents Chemother 2011; 55:4211−4217. [CrossRef]
• [30] Sugumar S, Ghosh V, Nirmala MJ, Mukherjee A, Chandrasekaran N. Ultrasonic emulsification of eucalyptus oil nanoemulsion: antibacterial activity against Staphylococcus aureus and wound heal-ing activity in Wistar rats. Ultrasonics Sonochem 2014;21:1044−1049. [CrossRef]
• [31] Meral R, Ceylan Z, Kose S. Limitation of microbial spoilage of rainbow trout fillets using character-ized thyme oil antibacterial nanoemulsions. J Food Safety 2019;39:e12644. [CrossRef]
• [32] Ceylan Z, Meral R, Kose S, Sengor G, Akinay Y, Durmus M, et al. Characterized nano-size curcumin and rosemary oil for the limitation microbial spoilage of rainbow trout fillets. LWT 2020;134:109965.[CrossRef]
• [33] Chua SK, Fu JY, Zulfakar MH, Ng MH, Hasan ZAA, et al. Optimisation and biological evalua-tion of palm glyceryl monocaprylate antimicro-bial nanoemulsion for combating S. aureus wound infection. J Mater Res Technol 2020;9:12804−12817. [CrossRef]
• [34] Alvarado H, Abrego G, Souto E, Garduno-Ramirez M, Clares B, Garcia M, et al. Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization. Colloids Surfaces B: Biointerfaces 2015;130:40−47.[CrossRef]
• [35] Clares B, Calpena AC, Parra A, Abrego G, Alvarado H, Fangueiro JF, et al. Nanoemulsions (NEs), lipo-somes (LPs) and solid lipid nanoparticles (SLNs) for retinyl palmitate: Effect on skin permeation. Int J Pharm 2014;473:591−598. [CrossRef]
• [36] Tadros T, Izquierdo P, Esquena J, Solans C. Formation and stability of nano-emulsions. Adv Colloid Interface Sci 2004;108:303−318. [CrossRef]
• [37] Mason TG, Wilking JN, Meleson K, Chang CB, Graves SM. Nanoemulsions: formation, structure, and physical properties. J Physics Condensed Matter 2006;18:R635. [CrossRef]
• [38] Severino P, Fangueiro J, Ferreira S, Basso R, Chaud M, Santana M, et al. Nanoemulsions and nanoparti-cles for non-melanoma skin cancer: effects of lipid materials. Clin Transl Oncol 2013;15:417−424.[CrossRef]
• [39] Macedo AS, Quelhas S, Silva AM, Souto EB. Nanoemulsions for delivery of flavonoids: formu-lation and in vitro release of rutin as model drug. Pharmaceutical Dev Technol 2014;19:677−680.[CrossRef]
• [40] Teixeira M, Severino P, Andreani T, Boonme P, Santini A, Silva A, et al. D-α-tocopherol nanoemul-sions: Size properties, rheological behavior, sur-face tension, osmolarity and cytotoxicity. Saudi Pharmaceutical J 2017;25:231−235. [CrossRef]
• [41] Nasir A. Nanotechnology and dermatology: Part II-risks of nanotechnology. Clin Dermatol 2010;28:581−588. [CrossRef]
• [42] Soriano-Ruiz JL, Calpena-Capmany AC, Cañadas-Enrich C, Bozal-de Febrer N, Suñer-Carbó J, Souto EB, et al. Biopharmaceutical profile of a clotrimazole nanoemulsion: Evaluation on skin and mucosae as anti-candidal agent. Int J Pharm 2019;554:105−115. [CrossRef]
• [43] Ghosh V, Saranya S, Mukherjee A, Chandrasekaran N. Cinnamon oil nanoemulsion formulation by ultrasonic emulsification: investigation of its bactericidal activity. J Nanosci Nanotechnol 2013;13:114−122. [CrossRef]
• [44] Adjonu R, Doran G, Torley P, Agboola S. Whey pro-tein peptides as components of nanoemulsions: A review of emulsifying and biological functionalities. J Food Eng 2014;122:15−27. [CrossRef]
• [45] Bernardi DS, Pereira TA, Maciel NR, Bortoloto J, Viera GS, Oliveira GC, et al. Formation and sta-bility of oil-in-water nanoemulsions containing rice bran oil: in vitro and in vivo assessments. J Nanobiotechnol 2011;9:1−9. [CrossRef]
• [46] Ehlers C, Ivens U, Møller M, Senderovitz T, Serup J. Females have lower skin surface pH than men: a study on the influence of gender, forearm site variation, right/left difference and time of the day on the skin surface pH. Skin Res Technol 2001;7:90−94. [CrossRef]
• [47] Lin C-Y, Chen L-W. Comparison of fuel properties and emission characteristics of two-and three-phase emulsions prepared by ultrasonically vibrating and mechanically homogenizing emulsification meth-ods. Fuel 2008;87:2154−2161. [CrossRef]
• [48] Gosh V, Mukherjee A, Chandrasekaran N. Ultrasonic emulsifivation of food-grade nanoemulsion formula-tion and evulation of its bactericial activity. Ultrasonic Sonochem 2013;20:338−344. [CrossRef]
• [49] Sugumar S, Nirmala J, Ghosh V, Anjali H, Mukherjee A, Chandrasekaran N. Bio‐based nanoemulsion for-mulation, characterization and antibacterial activity against food‐borne pathogens. J Basic Microbiol 2013;53:677−685. [CrossRef]
• [50] Moghimi R, Aliahmadi A, McClements DJ, Rafati H. Investigations of the effectiveness of nanoemul-sions from sage oil as antibacterial agents on some food borne pathogens. LWT-Food Sci Technol 2016;71:69−76. [CrossRef]
• [51] Garzoli S, Petralito S, Ovidi E, Turchetti G, Masci VL, Tiezzi A, et al. Lavandula x intermedia essen-tial oil and hydrolate: Evaluation of chemical com-position and antibacterial activity before and after formulation in nanoemulsion. Industrial Crops Products 2020;145:112068. [CrossRef]
• [52] Nirmala MJ, Durai L, Gopakumar V, Nagarajan R. Preparation of celery essential oil-based nanoemul-sion by ultrasonication and evaluation of its poten- tial anticancer and antibacterial activity. Int J Nanomed 2020;15:7651. [CrossRef]
• [53] Kumari S, Kumaraswamy R, Choudhary RC, Sharma S, Pal A, Raliya R, et al. Thymol nanoemul-sion exhibits potential antibacterial activity against bacterial pustule disease and growth pro-motory effect on soybean. Sci Rep 2018;8:1−12.[CrossRef]
• [54] de Oca-Ávalos JMM, Candal RJ, Herrera ML. Nanoemulsions: stability and physical properties. Curr Opin Food Sci 2017;16:1−6. [CrossRef]
• [55] Nishi T, Garima G, Sharma P, Nitin K. Nanoemulsions: a Review on Various Pharmaceutical Applications. Global J Pharmacol 2012;6:222−225.
• [56] Kildaci L, Budama-Kilinc Y, Kecel-Gunduz S, Altuntas E. Linseed oil nanoemulsions for treatment of atopic dermatitis disease: formulation, charac- terization, in vitro and in silico evaluations. J Drug Deliv Sci Technol 2021;64:102652. [CrossRef]
• [57] Müller R. Zeta Potential and Particle Charge in Laboratory Usage. 1996.
• [58] Karl B, Alkhatib Y, Beekmann U, Bellmann T, Blume G, Steiniger F, et al. Development and char-acterization of bacterial nanocellulose loaded with Boswellia serrata extract containing nanoemulsions as natural dressing for skin diseases. Int J Pharm 2020;587:119635. [CrossRef]
• [59] Ribeiro RC, Barreto SMAG, Ostrosky EA, Rocha-Filho PA, Veríssimo LM, Ferrari M. Production and characterization of cosmetic nanoemulsions containing Opuntia ficus-indica (L.) Mill extract as moisturizing agent. Molecules 2015;20:2492−2509.[CrossRef]
• [60] Ibrahim N, Raman I, Yusop MR. Effects of functional group of non-ionic surfactants on the stability of emulsion. Malaysian J Anal Sci 2015;19:261−267.
• [61] Ismail A, Nasr M, Sammour O. Nanoemulsion as a feasible and biocompatible carrier for ocu-lar delivery of travoprost: Improved pharmacoki- netic/pharmacodynamic properties. Int J Pharm 2020;583:119402. [CrossRef]
• [62] Mallick A, Gupta A, Hussain A, Aparajay P, Singh S, Singh SK, et al. Intranasal delivery of gabapentin loaded optimized nanoemulsion for augmented permeation. J Drug Deliv Sci Technol 2020;56:101606. [CrossRef]
• [63] Martini É. Nanoemulsões catiônicas como siste-mas de liberação de oligonucleotídeos: formulação e caracterização físico-química Master Thesis. 2005. [Spanish]
• [64] Nastiti CM, Ponto T, Abd E, Grice JE, Benson HA, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics 2017;9:37. [CrossRef]
• [65] Jiao J, Rhodes DG, Burgess DJ. Multiple emulsion sta-bility: pressure balance and interfacial film strength. J Colloid Interface Sci 2002;250:444−450. [CrossRef]
• [66] Shahnaz G, Hartl M, Barthelmes J, Leithner K, Sarti F, Hintzen F, et al. Uptake of phenothiazines by the harvested chylomicrons ex vivo model: Influence of self-nanoemulsifying formulation design. Eur J Pharm Biopharm 2011;79:171−180. [CrossRef]
• [67] Rachmawati H, Budiputra DK, Mauludin R. Curcumin nanoemulsion for transdermal appli-cation: formulation and evaluation. Drug Dev Ind Pharm 2015;41:560−566. [CrossRef]
• [68] Yilmaz A, Meral R, Kabli M, Ermis E, Akman PK, Dertli E, et al. Fabrication and characterization of bioactive nanoemulsion-based delivery Systems. Emerg Mater Res 2021:1−8. [CrossRef]
• [69] Donsì F, Ferrari G. Essential oil nanoemulsions as antimicrobial agents in food. J Biotechnol 2016;233:106−120. [CrossRef]
• [70] Balasubramani S, Rajendhiran T, Moola AK, Diana RKB. Development of nanoemulsion from Vitex negundo L. essential oil and their efficacy of antioxidant, antimicrobial and larvicidal activ-ities (Aedes aegypti L.). Environ Sci Pollut Res 2017;24:15125−15133. [CrossRef]
• [71] Krishnamoorthy R, Athinarayanan J, Periasamy VS, Adisa AR, Al-Shuniaber MA, Gassem MA, et al. Antimicrobial activity of nanoemulsion on drug-re-sistant bacterial pathogens. Microbial Pathogenesis 2018;120:85−96. [CrossRef]
• [72] Pathania R, Kaushik R, Khan MA. Essential oil nanoemulsions and their antimicrobial and food applications. Curr Res Nutr Food Sci J 2018;6:626−643. [CrossRef]
• [73] Majeed H, Liu F, Hategekimana J, Sharif HR, Qi J, Ali B, et al. Bactericidal action mechanism of nega-tively charged food grade clove oil nanoemulsions. Food Chem 2016;197:75−83. [CrossRef]
• [74] Dillen K, Bridts C, Van der Veken P, Cos P, Vandervoort J, Augustyns K, et al. Adhesion of PLGA or Eudragit®/PLGA nanoparticles to Staphylococcus and Pseudomonas. Int J Pharm 2008;349:234−240.[CrossRef]
• [75] Ozogul Y, Boğa EK, Akyol I, Durmus M, Ucar Y, Regenstein JM, et al. Antimicrobial activity of thyme essential oil nanoemulsions on spoilage bac-teria of fish and food-borne pathogens. Food Biosci 2020;36:100635. [CrossRef]
• [76] Lee KH, Lee J-S, Kim ES, Lee HG. Preparation, characterization, and food application of rosemary extract-loaded antimicrobial nanoparticle disper-sions. LWT 2019;101:138−144. [CrossRef]
• [77] Karimi N, Ghanbarzadeh B, Hamishehkar H, Mehramuz B, Kafil HS. Antioxidant, antimicrobial and physicochemical properties of turmeric extract-loaded nanostructured lipid carrier (NLC). Colloid Interface Sci Commun 2018;22:18−24. [CrossRef]
• [78] Fernández‐Campos F, Clares Naveros B, Lopez Serrano O, Alonso Merino C, Calpena Campmany A. Evaluation of novel nystatin nanoemulsion for skin candidosis infections. Mycoses 2013;56:70−81. [CrossRef]
• [79] Seibert JB, Bautista-Silva JP, Amparo TR, Petit A, Pervier P, dos Santos Almeida JC, et al. Development of propolis nanoemulsion with antioxidant and anti- microbial activity for use as a potential natural pre-servative. Food Chem 2019;287:61−67. [CrossRef]
• [80] Liang R, Xu S, Shoemaker CF, Li Y, Zhong F, Huang Q. Physical and antimicrobial properties of pep-permint oil nanoemulsions. J Agric Food Chem 2012;60:7548−7555. [CrossRef]
• [81] Li, ZH, Cai M, Liu Y-S, Sun P-L. Development of finger citron (Citrus medica L. var. sarcodactylis) essential oil loaded nanoemulsion and its antimi-crobial activity. Food Control 2018;94:317−323.[CrossRef]