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Probiotics and Antimicrobial Proteins

, Volume 11, Issue 1, pp 310–316 | Cite as

Antibacterial Activity of Vancomycin Encapsulated in Poly(DL-lactide-co-glycolide) Nanoparticles Using Electrospraying

  • Elzaan Booysen
  • Martin Bezuidenhout
  • Anton Du Preez van Staden
  • Dimiter Dimitrov
  • Shelly M. Deane
  • Leon M. T. DicksEmail author
Article

Abstract

Vancomycin is often used to treat infections caused by β-lactam-resistant bacteria. However, methicillin-resistant strains of Staphylococcus aureus (MRSA) acquired resistance to vancomycin, rendering it less effective in the treatment of serious infections. In the search for novel antibiotics, alternative delivery mechanisms have also been explored. In this study, we report on the encapsulation of vancomycin in PLGA [poly(DL-lactide-co-glycolide)] nanoparticles by electrospraying. The nanoparticles were on average 247 nm in size with small bead formations on the surface. Clusters of various sizes were visible under the SEM (scanning electron microscope). Vancomycin encapsulated in PLGA (VNP) was more effective in inhibiting the growth of S. aureus Xen 31 (MRSA) and S. aureus Xen 36 than un-encapsulated vancomycin. Encapsulated vancomycin had a minimum inhibitory concentration (MIC) of 1 μg/mL against MRSA compared to 5 μg/mL of free vancomycin. At least 70% (w/w) of the vancomycin was encapsulated. Thirty percent of the vancomycin was released within the first 144 h, followed by slow release over 10 days. Vancomycin encapsulated in PLGA nanoparticles may be used to treat serious infections.

Keywords

Staphylococcus aureus PLGA Nanoparticles Electrospraying 

Notes

Acknowledgements

The Central Analytical Facility (CAF) of Stellenbosch University for assistance with ultra-high-pressure liquid chromatography (UHPLC) and liquid chromatography mass spectrometry (LCMS).

Funding Information

This work was financed by the FraunHofer Institute for Machine Tools and Forming Technology (IWU), Chemnitz, Germany.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interest.

References

  1. 1.
    Wagner V, Dullaart A, Bock A-K, Zweck A (2006) The emerging nanomedicine landscape. Nat Biotechnol 24:1211–1217CrossRefGoogle Scholar
  2. 2.
    Yao S, Liu H, Yu S, Li Y, Wang X, Wang L (2016) Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior. Regen Biomater 3:309–317CrossRefGoogle Scholar
  3. 3.
    Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–522CrossRefGoogle Scholar
  4. 4.
    Dillen K, Vandervoort J, Van Den Mooter G, Verheyden L, Ludwig A (2004) Factorial design, physicochemical characterisation and activity of ciprofloxacin-PLGA nanoparticles. Int J Pharm 275:171–187CrossRefGoogle Scholar
  5. 5.
    Salouti M, Ahangari A (2014) Nanoparticle based drug delivery systems for treatment of infectious diseases. In: Sezer AD (ed) Application of nanotechnology in drug delivery. InTech, pp 155–192Google Scholar
  6. 6.
    Zakeri-milani P, Loveymi BD, Jelvehgari M, Valizadeh H (2013) The characteristics and improved intestinal permeability of vancomycin PLGA-nanoparticles as colloidal drug delivery system. Colloids Surf B Biointerfaces 103:174–181.  https://doi.org/10.1016/j.colsurfb.2012.10.021 CrossRefGoogle Scholar
  7. 7.
    Adair JH, Parette MP, Altinoglu EI, Kester M (2010) Nanoparticulate alternatives for drug delivery. ACS Nano 4:4967–4970CrossRefGoogle Scholar
  8. 8.
    Farokhzad OC, Langer R (2009) Impact of aanotechnology on drug delivery. ACS Nano 3:16–20CrossRefGoogle Scholar
  9. 9.
    Turos E, Reddy GSK, Greenhalgh K, Ramaraju P, Abeylath SC, Jang S, Dickey S, Lim DV (2007a) Penicillin-bound polyacrylate nanoparticles: restoring the activity of ß-lactam antibiotics against MRSA. Bioorg Med Chem Lett 17:3468–3472.  https://doi.org/10.1016/j.bmcl.2007.03.077 CrossRefGoogle Scholar
  10. 10.
    Turos E, Shim JY, Wang Y, Greenhalgh K, Reddy GSK, Dickey S, Lim DV (2007b) Antibiotic-conjugated polyacrylate nanoparticles: new opportunities for development of anti-MRSA agents. Bioorg Med Chem Lett 17:53–56CrossRefGoogle Scholar
  11. 11.
    Hartsel S, Bolard J (1996) Amphotericin B: new life for an old drug. Trends Pharmacol Sci 17(12):445–449CrossRefGoogle Scholar
  12. 12.
    Cavalli R, Gasco MR, Chetoni P, Burgalassi S, Saettone MF (2002) Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. Int J Pharm 238:241–245CrossRefGoogle Scholar
  13. 13.
    Fielding RM, Lewis RO, Moon-McDermott L (1998) Altered tissue distribution and elimination of amikacin encapsulated in unilamellar, low clearance liposomes (MiKasome®). Pharm Res 15:1775–1781CrossRefGoogle Scholar
  14. 14.
    Jain D, Banerjee R (2008) Comparison of ciprofloxacin hydrochloride-loaded protein, lipid, and chitosan nanoparticles for drug delivery. J Biomed Mater Res B Appl Biomater 86:105–112CrossRefGoogle Scholar
  15. 15.
    Kim H, Jones MN (2004) The delivery of benzyl penicillin to Staphylococcus aureus biofilms by use of liposomes. J Liposome Res 14:123–139CrossRefGoogle Scholar
  16. 16.
    Magallanes M, Dijkstra J, Fierer J (1993) Liposome-incorporated ciprofloxacin in treatment of murine salmonellosis. Antimicrob Agents Chemother 37:2293–2297CrossRefGoogle Scholar
  17. 17.
    Omri A, Suntres ZE, Shek PN (2002) Enhanced activity of liposomal polymyxin B against Pseudomonas aeruginosa in a rat model of lung infection. Biochem Pharmacol 64:1407–1413CrossRefGoogle Scholar
  18. 18.
    Pandey R, Khuller GK (2005) Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis 85:227–234CrossRefGoogle Scholar
  19. 19.
    Pandey R, Sharma A, Zahoor A, Sharma S, Khuller GK, Prasad B (2003) Poly (DL-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis. J Antimicrob Chemother 52:981–986CrossRefGoogle Scholar
  20. 20.
    Sanna V, Gavini E, Cossu M, Rassu G, Giunchedi P (2007) Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies. J Pharm Pharmacol 59:1057–1064CrossRefGoogle Scholar
  21. 21.
    Eckert R (2011) Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microbiol 6:635–651CrossRefGoogle Scholar
  22. 22.
    Carvalho CA, Olivares-Ortega C, Soto-Arriaza MA, Carmona-Ribeiro AM (2012) Interaction of gramicidin with DPPC/DODAB bilayer fragments. Biochim Biophys Acta 1818:3064–3071CrossRefGoogle Scholar
  23. 23.
    Ragioto DAMT, Carrasco LDM, Carmona-Ribeiro AM (2014) Novel gramicidin formulations in cationic lipid as broad-spectrum microbicidal agents. Int J Nanomedicine 9:3183–3192Google Scholar
  24. 24.
    Davies B, Cohen J (2011) Endotoxin removal devices for the treatment of sepsis and septic shock. Lancet Infect Dis 11:65–71CrossRefGoogle Scholar
  25. 25.
    Shoji H (2003) Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin). Ther Apher Dial 7:108–114CrossRefGoogle Scholar
  26. 26.
    Cruciani M, Gatti G, Lazzarini L, Furlan G, Broccali G, Malena M, Franchini C, Concia E (1996) Penetration of vancomycin into human lung tissue. J Antimicrob Chemother 38:865–869CrossRefGoogle Scholar
  27. 27.
    Pumerantz A, Muppidi K, Agnihotri S, Guerra C, Venketaraman V, Wang J, Betageri G (2011) Preparation of liposomal vancomycin and intracellular killing of methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents 37:140–144CrossRefGoogle Scholar
  28. 28.
    Nicolosi D, Scalia M, Nicolosi VM, Pignatello R (2010) Encapsulation in fusogenic liposomes broadens the spectrum of action of vancomycin against Gram-negative bacteria. Int J Antimicrob Agents 35:553–558CrossRefGoogle Scholar
  29. 29.
    Ma T, Shang BC, Tang H, Zhou TH, Xu GL, Li HL, Chen QH, Xu YQ (2011) Nano-hydroxyapatite/chitosan/konjac glucomannan scaffolds loaded with cationic liposomal vancomycin: preparation, in vitro release and activity against Staphylococcus aureus biofilms. J Biomater Sci Polym Ed 22:1669–1681CrossRefGoogle Scholar
  30. 30.
    Velkov T, Roberts KD, Nation RL, Thompson PE, Li J (2013) Pharmacology of polymyxins: new insights into an “old” class of antibiotics. Future Microbiol 8:711–724CrossRefGoogle Scholar
  31. 31.
    Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S, Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M, Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M, Welfare W, Livermore DM, Woodford N (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10:597–602CrossRefGoogle Scholar
  32. 32.
    Kirby A, Graham R, Williams NJ, Wootton M, Broughton CM, Alanazi M, Anson J, Neal TJ, Parry CM (2010) Staphylococcus aureus with reduced glycopeptide susceptibility in Liverpool, UK. J Antimicrob Chemother 65:721–724CrossRefGoogle Scholar
  33. 33.
    Hachicha W, Kodjikian L, Fessi H (2006) Preparation of vancomycin microparticles: importance of preparation parameters. Int J Pharm 324:176–184CrossRefGoogle Scholar
  34. 34.
    Lotfipour F, Abdollahi S, Jelvehgari M, Valizadeh H, Hassan M, Milani M (2013) Study of antimicrobial effects of vancomycin loaded PLGA nanoparticles against Enterococcus clinical isolates. Drug Res (Stuttg) 64:348–352.  https://doi.org/10.1055/s-0033-1358747 CrossRefGoogle Scholar
  35. 35.
    van Staden ADP (2011) Developing bone cement implants impregnated with bacteriocins for prevention of infections. MSc thesis, Stellenbosch UniversityGoogle Scholar
  36. 36.
    Branowska I, Wilczek A, Baranowski J (2010) Rapid UHPLC method for simultaneous determination of vancomycin, terbinafine, spironolactone, furosemide and their metabolites: application to human plasma and urine. Anal Sci 26:755–759CrossRefGoogle Scholar
  37. 37.
    Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 48:5–16CrossRefGoogle Scholar
  38. 38.
    Mccall RL, Sirianni RW (2013) PLGA nanoparticles formed by single- or double-emulsion with vitamin E- TPGS. J Vis Exp 82:1–8Google Scholar
  39. 39.
    Barichello JM, Morishita M, Takayama K, Nagai T (1999) Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm 25:471–476CrossRefGoogle Scholar
  40. 40.
    Hans M, Lowman A (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327CrossRefGoogle Scholar
  41. 41.
    García-Díaz M, Foged C, Nielsen HM (2015) Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids. Int J Pharm 482:84–91CrossRefGoogle Scholar
  42. 42.
    Menale C, Piccolo MT, Favicchia I, Aruta MG, Baldi A, Nicolucci C, Barba V, Mita DG, Crispi S, Diano N (2015) Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells. Pharm Res 32:362–374CrossRefGoogle Scholar
  43. 43.
    Luo C, Okubo T, Nangrejo M, Edirisinghe M, Valizadeh H, Hassan M, Milani M (2015) Preparation of polymeric nanoparticles by novel electrospray nanoprecipitation. Polym Int 64:183–187CrossRefGoogle Scholar
  44. 44.
    Ahire JJ, Neppalli R, Heunis TDJ, van Reenen AJ, Dicks LMT (2014) 2,3-Dihydroxybenzoic acid electrospun into poly (D, L-lactide) (PDLLA)/poly (ethylene oxide) (PEO) nanofibers inhibited the growth of Gram-positive and Gram-negative bacteria. Curr Microbiol 69:587–593CrossRefGoogle Scholar
  45. 45.
    Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 3:1377–1397CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Elzaan Booysen
    • 1
  • Martin Bezuidenhout
    • 2
  • Anton Du Preez van Staden
    • 3
  • Dimiter Dimitrov
    • 2
  • Shelly M. Deane
    • 1
  • Leon M. T. Dicks
    • 1
    Email author
  1. 1.Department of Microbiology, Faculty of Natural SciencesStellenbosch UniversityStellenboschSouth Africa
  2. 2.Department of Industrial Engineering, Faculty of EngineeringStellenbosch UniversityStellenboschSouth Africa
  3. 3.Department of Physiological Science, Faculty of Natural SciencesStellenbosch UniversityStellenboschSouth Africa

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