Skip to main content
SpringerLink
Log in

Preparation and Evaluation of Biomineral-Binding Antibiotic Liposomes

  • Living reference work entry
  • First Online:
Liposome-Based Drug Delivery Systems

Part of the book series: Biomaterial Engineering ((BIOENG))

Abstract

The prevention and treatment of bacterial contamination induced bone infection is challenging due to the lack of osteotropicity of available antimicrobials. This protocol describes a novel biomineral-binding liposomal (BBL) platform for the efficient delivery of antimicrobials to the skeletal tissues. The biomineral-binding lipid, alendronate-tri(ethylene- glycol)-cholesterol conjugate (ALN-TEG-Chol), was synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition, a versatile “click” reaction. Using ALN-TEG-Chol, BBL-containing antimicrobial oxacillin was then successfully developed using extrusion and sonication methods. Oxacillin-loaded BBL showed fast and strong binding to hydroxyapatite particles (model bone surface), and demonstrated significantly better preventive efficacy against bacterial colonization when challenged with Staphylococcus aureus when compared to that of free oxacillin and non-BBL. This suggests that the development of biomineral-binding liposomal formulations of antimicrobials may be used in conjunction with orthopedic implants or bone-grafting materials to prevent osteomyelitis associated with orthopedic surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  • Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB (2005) The liposomal formulation of doxorubicin. Methods Enzymol 391:71–97

    Article  Google Scholar 

  • Boucher H, Miller LG, Razonable RR (2010) Serious infections caused by methicillin-resistant Staphylococcus aureus. Clin Infect Dis 51(Suppl 2):S183–S197

    Article  Google Scholar 

  • Diaz-Rodriguez P, Landin M, Rey-Rico A, Couceiro J, Coenye T, Gonzalez P, Serra J, Lopez-Alvarez M, Leon B (2011) Bio-inspired porous SiC ceramics loaded with vancomycin for preventing MRSA infections. J Mater Sci Mater Med 22(2):339–347

    Article  Google Scholar 

  • El-Husseiny M, Patel S, MacFarlane RJ, Haddad FS (2011) Biodegradable antibiotic delivery systems. J Bone Joint Surg Br 93(2):151–157

    Article  Google Scholar 

  • Gabizon A, Horowitz AT, Goren D, Tzemach D, Shmeeda H, Zalipsky S (2003) In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing mice. Clin Cancer Res 9(17):6551–6559

    Google Scholar 

  • Gaitanis A, Staal S (2010) Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol 624:385–392

    Article  Google Scholar 

  • Gast K, Zirwer D, Ladhoff AM, Schreiber J, Koelsch R, Kretschmer K, Lasch J (1982) Auto-oxidation-induced fusion of lipid vesicles. Biochim Biophys Acta 686(1):99–109

    Article  Google Scholar 

  • Hein CD, Liu XM, Wang D (2008) Click chemistry, a powerful tool for pharmaceutical sciences. Pharm Res 25(10):2216–2230

    Article  Google Scholar 

  • Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1(3):297–315

    Article  Google Scholar 

  • Jett BD, Hatter KL, Huycke MM, Gilmore MS (1997) Simplified agar plate method for quantifying viable bacteria. BioTechniques 23(4):648–650

    Google Scholar 

  • Khoo X, O’Toole GA, Nair SA, Snyder BD, Kenan DJ, Grinstaff MW (2010) Staphylococcus aureus resistance on titanium coated with multivalent PEGylated-peptides. Biomaterials 31(35): 9285–9292

    Article  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 40(11):2004–2021

    Article  Google Scholar 

  • Kumar VA, Fausto AK, Mitchell N, Robbins R (2007) Basic pathology, 8th edn. Elsevier Health Sciences, Philadelphia, pp 810–811

    Google Scholar 

  • Lew DP, Waldvogel FA (1997) Osteomyelitis. N Engl J Med 336(14):999–1007

    Article  Google Scholar 

  • Liu XM, Thakur A, Wang D (2007) Efficient synthesis of linear multifunctional poly(ethylene glycol) by copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Biomacromolecules 8(9): 2653–2658

    Article  Google Scholar 

  • Liu XM, Wiswall AT, Rutledge JE, Akhter MP, Cullen DM, Reinhardt RA, Wang D (2008) Osteotropic beta-cyclodextrin for local bone regeneration. Biomaterials 29(11):1686–1692

    Article  Google Scholar 

  • Liu XM, Zhang Y, Chen F, Khutsishvili I, Fehringer EV, Marky LA, Bayles KW, Wang D (2012) Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes. Pharm Res 29(11):3169–3179

    Article  Google Scholar 

  • Ohvo-Rekila H, Ramstedt B, Leppimaki P, Slotte JP (2002) Cholesterol interactions with phospholipids in membranes. Prog Lipid Res 41(1):66–97

    Article  Google Scholar 

  • Pan H, Sima M, Kopeckova P, Wu K, Gao S, Liu J, Wang D, Miller SC, Kopecek J (2008) Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates. Mol Pharm 5(4):548–558

    Article  Google Scholar 

  • Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed Engl 41(14):2596–2599

    Article  Google Scholar 

  • Takahashi T, Yokogawa K, Sakura N, Nomura M, Kobayashi S, Miyamoto K (2008) Bone-targeting of quinolones conjugated with an acidic oligopeptide. Pharm Res 25(12):2881–2888

    Article  Google Scholar 

  • Tanaka KS, Houghton TJ, Kang T, Dietrich E, Delorme D, Ferreira SS, Caron L, Viens F, Arhin FF, Sarmiento I et al (2008) Bisphosphonated fluoroquinolone esters as osteotropic prodrugs for the prevention of osteomyelitis. Bioorg Med Chem 16(20):9217–9229

    Article  Google Scholar 

  • Torchilin VP (2005) Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov 4(2):145–160

    Article  Google Scholar 

  • Wang D, Miller S, Sima M, Kopeckova P, Kopecek J (2003) Synthesis and evaluation of water-soluble polymeric bone-targeted drug delivery systems. Bioconjug Chem 14(5):853–859

    Article  Google Scholar 

  • Wang D, Miller SC, Kopecek J (2005) Targeted drug delivery for musculoskeletal diseases. Adv Drug Deliv Rev 57(7):935–937

    Article  Google Scholar 

  • Wu P, Grainger DW (2006) Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials 27(11):2450–2467

    Article  Google Scholar 

  • Yoshinari M, Kato T, Matsuzaka K, Hayakawa T, Shiba K (2010) Prevention of biofilm formation on titanium surfaces modified with conjugated molecules comprised of antimicrobial and titanium-binding peptides. Biofouling 26(1):103–110

    Article  Google Scholar 

  • Zhang S, Gangal G, Uludag H (2007) ‘Magic bullets’ for bone diseases: progress in rational design of bone-seeking medicinal agents. Chem Soc Rev 36(3):507–531

    Article  Google Scholar 

Download references

Acknowledgments

The preparation of this book chapter was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health under award number R01 AR62680. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA

    Xin-Ming Liu, Ke Ren & Dong Wang

  2. Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

    Geoffrey Wu

Authors
  1. Xin-Ming Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ke Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Geoffrey Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ke Ren .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics, Peking University Department of Pharmaceutics, Beijing, China

    Wan-Liang Lu

  2. Department of Pharmaceutics, Peking University Department of Pharmaceutics, Beijing, China

    Xiang-Rong Qi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer-Verlag GmbH Germany

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Liu, XM., Ren, K., Wu, G., Wang, D. (2018). Preparation and Evaluation of Biomineral-Binding Antibiotic Liposomes. In: Lu, WL., Qi, XR. (eds) Liposome-Based Drug Delivery Systems. Biomaterial Engineering. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49231-4_17-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-49231-4_17-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49231-4

  • Online ISBN: 978-3-662-49231-4

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation