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Colloid and Polymer Science

, Volume 296, Issue 5, pp 951–960 | Cite as

Triclosan nanoparticles via emulsion-freeze-drying for enhanced antimicrobial activity

  • Ulrike Wais
  • Margarete M. Nawrath
  • Alexander W. Jackson
  • Haifei Zhang
Original Contribution
  • 99 Downloads

Abstract

Low water solubility and poor bioavailability of hydrophobic pharmaceuticals are significant problems in drug formulation. This research presents a bottom-up route to prepare nanoparticles of hydrophobic actives which is synthetically straightforward, robust, and can be applied to a range of active molecules. A series of amphiphilic branched diblock copolymers have been prepared via the conventional radical polymerization of a vinyl monomer (styrene, butylmethacrylate, or N-isopropylacrylamide) and a corresponding divinyl cross-linker facilitated by a poly(ethylene glycol)-based macro-initiator. These materials were employed as stabilizers in the emulsion-freeze-drying methodology to prepare nanoparticles of hydrophobic pharmaceuticals. It is demonstrated that these branched diblock copolymers are able to facilitate the formation of Triclosan nanoparticles which display enhanced antimicrobial activity against Candida albicans, when compared to non-processed (used as received) Triclosan. This process requires significantly lower levels of stabilizer compared to previously reported surfactant/polymer systems after optimization of polymer properties and morphology.

Keywords

Emulsion-freeze-drying Branched diblock copolymers Bottom-up Nanomedicine Antimicrobial 

Notes

Acknowledgments

Ulrike Wais acknowledges the joint PhD studentship between the University of Liverpool and the A*Star Research Attachment Program (ARAP) scholarship. The authors would like to thank Wendy Rusli (of A* Star, Institute of Chemical and Engineering Sciences) for performing cryo-TEM analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

396_2018_4312_MOESM1_ESM.docx (1.6 mb)
ESM 1 1H NMR spectra, and additional optical microscopy and SEM image (DOCX 1640 kb)

References

  1. 1.
    Loftssona T, Brewsterb ME (2010) Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol 62:1607–1621CrossRefGoogle Scholar
  2. 2.
    Lipinski CA, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 23:3–25CrossRefGoogle Scholar
  3. 3.
    Kalepu S, Nekkanti V (2015) Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B 5:442–453CrossRefGoogle Scholar
  4. 4.
    Hodgson J (2001) ADMET--turning chemicals into drugs. Nature Biotechnol 19:722–726CrossRefGoogle Scholar
  5. 5.
    Ren W, Cheng W, Wang G, Liu Y (2017) Developments in antimicrobial polymers. J Polym Sci A Polym Chem 55:632–639CrossRefGoogle Scholar
  6. 6.
    Turos E, Reddy GSK, Greenhalgh K, Ramaraju P, Abeylath SC, Jang S, Dickey S, Lim DV (2007) Penicillin-bound polyacrylate nanoparticles: restoring the activity of β-lactam antibiotics against MRSA. Bioorg Med Chem Lett 17:3468–3472CrossRefGoogle Scholar
  7. 7.
    Radovic-Moreno AF, Lu TK, Puscasu VA, Yoon CJ, Langer R, Farokhzad OC (2012) Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics. ACS Nano 6:4279–4287CrossRefGoogle Scholar
  8. 8.
    Pinto-Alphandary H, Andremont A, Couvreur P (2000) Targeted delivery of antibiotics using liposomes and nanoparticles: research and applications. Int J Antimicrob Agents 13:155–168CrossRefGoogle Scholar
  9. 9.
    Langowska K, Palivan CG, Meier W (2013) Polymer nanoreactors shown to produce and release antibiotics locally. Chem Commun 49:128–130CrossRefGoogle Scholar
  10. 10.
    Zhang J, Pin Chen Y, Miller KP, Ganewatta MS, Bam M, Yan Y, Nagarkatti M, Decho AW, Tang C (2014) Antimicrobial metallopolymers and their bioconjugates with conventional antibiotics against multidrug-resistant bacteria. J Am Chem Soc 136:4873–4876CrossRefGoogle Scholar
  11. 11.
    Wais U, Jackson AW, He T, Zhang H (2016). Nano 8:1746–1769Google Scholar
  12. 12.
    Tran T-H, Nguyen CT, Gonzalez-Fajardo L, Hargrove D, Song D, Deshmukh P, Mahajan L, Ndaya D, Lai L, Kasi RM, Lu X (2014) Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors. Biomacromolecules 15:4363–4375CrossRefGoogle Scholar
  13. 13.
    Williams DF (1982) Biodegradation of surgical polymers. J Mater Sci 17:1233–1246CrossRefGoogle Scholar
  14. 14.
    Lee ALZ, Venkataraman S, Sirat SBM, Gao S, Hedrick JL, Yang YY (2012) The use of cholesterol-containing biodegradable block copolymers to exploit hydrophobic interactions for the delivery of anticancer drugs. Biomaterials 33:1921–1928CrossRefGoogle Scholar
  15. 15.
    Yu Y, He Y, Xu B, He Z, Zhang Y, Chen Y, Yang Y, Xie Y, Zheng Y, He G, He J, Song X (2013) Self-assembled methoxy poly(ethylene glycol)-cholesterol micelles for hydrophobic drug delivery. J Pharm Sci 102:1054–1062CrossRefGoogle Scholar
  16. 16.
    Scherphof GL, Dijkstra JAN, Spanjer HH, Derksen JTP, Roerdink FH (1985) Uptake and intracellular processing of targeted and nontargeted liposomes by rat Kupffer cells in vivo and in vitro. Ann N Y Acad Sci 446:368–384CrossRefGoogle Scholar
  17. 17.
    Allen TM, Hansen C, Martin F, Redemann C, Yau-Young A (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta 1066:29–36CrossRefGoogle Scholar
  18. 18.
    McDonald TO, Tatham LM, Southworth FY, Giardiello M, Martin P, Liptrott NJ, Owen A, Rannard SP (2013) High-throughput nanoprecipitation of the organic antimicrobial triclosan and enhancement of activity against Escherichia coli. J Mater Chem B 1:4455–4465CrossRefGoogle Scholar
  19. 19.
    Maa Y-F, Nguyen P-A, Sweeney T, Shire SJ, Hsu CC (1999) Protein inhalation powders: spray drying vs spray freeze drying. Pharm Res 16:249–254CrossRefGoogle Scholar
  20. 20.
    Chawla A, Taylor KMG, Newton JM, Johnson MCR (1994) Production of spray dried salbutamol sulphate for use in dry powder aerosol formulation. Int J Pharm 108:233–240CrossRefGoogle Scholar
  21. 21.
    Merisko-Liversidge E, Liversidge GG (2011) Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev 63:427–440CrossRefGoogle Scholar
  22. 22.
    Brough C, Williams Iii RO (2013) Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int J Pharm 453:157–166CrossRefGoogle Scholar
  23. 23.
    Sinha B, Müller RH, Möschwitzer JP (2013) Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm 453:126–141CrossRefGoogle Scholar
  24. 24.
    Chan H-K, Kwok PCL (2011) Production methods for nanodrug particles using the bottom-up approach. Adv Drug Deliv Rev 63:406–416CrossRefGoogle Scholar
  25. 25.
    Sultana N, Wang M (2008) Fabrication of HA/PHBV composite scaffolds through the emulsion freezing/freeze-drying process and characterisation of the scaffolds. J Mater Sci Mater Med 19:2555–2561CrossRefGoogle Scholar
  26. 26.
    Sultana N, Wang M (2012). Biofabrication 4:1–14CrossRefGoogle Scholar
  27. 27.
    Wanga T, Wang N, Wang T, Sun W, Li T (2011) Preparation of submicron liposomes exhibiting efficient entrapment of drugs by freeze-drying water-in-oil emulsions. Chem Phys Lipids 164:151–157CrossRefGoogle Scholar
  28. 28.
    Wang T, Deng Y, Geng Y, Gao Z, Zou J, Wang Z (2006) Preparation of submicron unilamellar liposomes by freeze-drying double emulsions. Biochim Biophys Acta 1758:222–231CrossRefGoogle Scholar
  29. 29.
    Grant N, Zhang H (2011) Poorly water-soluble drug nanoparticles via an emulsion-freeze-drying approach. J Colloid Interface Sci 356:573–578CrossRefGoogle Scholar
  30. 30.
    Zhang H, Wang D, Butler R, Campbell NL, Long J, Tan B, Duncalf DJ, Foster AJ, Hopkinson A, Taylor D, Angus D, Cooper AI, Rannard SP (2008) Formation and enhanced biocidal activity of water-dispersable organic nanoparticles. Nat Nanotechnol 3:506–511CrossRefGoogle Scholar
  31. 31.
    Wais U, Jackson AW, Zuo Y, Xiang Y, He T, Zhang H (2016) Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles. J Control Release 222:141–150CrossRefGoogle Scholar
  32. 32.
    Martins N, Ferreira ICFR, Barros L, Silva S, Henriques M (2014) Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment. Mycopathologia 177:223–240CrossRefGoogle Scholar
  33. 33.
    Erdogan A, Rao SSC (2015). Curr Gastroenterol Rep 17:1–7CrossRefGoogle Scholar
  34. 34.
    Teagarden DL, Baker DS (2002) Practical aspects of lyophilization using non-aqueous co-solvent systems. Eur J Pharm Sci 15:115–133CrossRefGoogle Scholar
  35. 35.
    ICH, ICH harmonised tripartite guideline-impurities: guideline for residual solvents Q3C (R5)Google Scholar
  36. 36.
    Verma A, Stellacci F (2010) Effect of surface properties on nanoparticleâcell interactions. Small 6:12–21CrossRefGoogle Scholar
  37. 37.
    Pfaller MA, Diekema DJ (2007) Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin Microbiol Rev 20:133–163CrossRefGoogle Scholar
  38. 38.
    R. Singh and A. Chakrabarti, In: C. albicans: Cellular and molecular biology, ed. R. Prasad, Springer International Publishing, Switzerland, 2017 3, pp 25–40Google Scholar
  39. 39.
    Loftsson T, Leeves N, Bjornsdottir B, Duffy L, Masson M (1999) Effect of cyclodextrins and polymers on triclosan availability and substantivity in toothpastes in vivo. J Pharm Sci 88:1254–1258CrossRefGoogle Scholar
  40. 40.
    Noyes AA, Whitney WR (1897) The rate of solution of solid substances in their own solutions. J Am Chem Soc 19:930–934CrossRefGoogle Scholar
  41. 41.
    Maleki Dizaj S, Vazifehasl Z, Salatin S, Adibkia K, Javadzadeh Y (2015). Res Pharm Sci 10:95–108Google Scholar
  42. 42.
    Heng D, Cutler DJ, Chan HK, Raper JA (2008) What is a suitable dissolution method for drug nanoparticles? Pharm Res 25:1696–1701CrossRefGoogle Scholar
  43. 43.
    Prabhu S, Poulose EK (2012). Int Nano Lett 2:32–41CrossRefGoogle Scholar
  44. 44.
    Levy SB, Marshall B (2004) Antibacterial resistance worldwide: causes, challenges and responses. Nat Med 10:S122–S129CrossRefGoogle Scholar
  45. 45.
    Barbosa TM, Levy SB (2000) The impact of antibiotic use on resistance development and persistence. Drug Resist Updat 3:303–311CrossRefGoogle Scholar
  46. 46.
    Dann AB, Hontela A (2011) Triclosan: environmental exposure, toxicity and mechanisms of action. J Appl Toxicol 31:285–311CrossRefGoogle Scholar
  47. 47.
    Jamil B, Imran M (2018) Factors pivotal for designing of nanoantimicrobials: an exposition. Crit Rev Micobiol 44:79–94CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of LiverpoolLiverpoolUK
  2. 2.Institute of Chemical and Engineering ScienceJurong IslandSingapore
  3. 3.Institute of BiochemistryUniversity of LeipzigLeipzigGermany

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