Skip to main content
SpringerLink
Log in

Surface Modifications of Liposomes for Drug Targeting

  • Chapter
  • First Online:
Surface Modification of Nanoparticles for Targeted Drug Delivery

Abstract

Medical treatment through the use of pharmaceuticals is dependent on the ability of therapeutic agents to reach their intended targets while evading unintended interactions, endosomal sequestration, and degradation. By developing targeted therapies, our treatments of different diseases can be tremendously improved in ways that not only enhance the functionality of relevant drugs, but also improve the patients’ experiences. Liposomes are nanocarriers that encapsulate their payloads, protecting active ingredients from biological environments and degradation. Their use in nanomedicine has the ability to reshape drug administration, from improved specificity and prolonged circulation to decreased cytotoxicity and fewer negative side effects. The efficacy and functionality of liposomes can be further refined and enhanced through surface modification. By conjugating liposomes with various moieties, drug delivery can become a much more targeted process.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 44.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 59.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Fakhar ud, D., et al. (2017). Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. International Journal of Nanomedicine, 12, 7291–7309. PMC. Web: August 28, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634382/

  2. Siafaka, P. I., Okur, N. Ü., Karavas, E., & Bikiaris, D. N. (2016). Surface modified multifunctional and stimuli responsive nanoparticles for drug targeting: Current status and uses. International Journal of Molecular Sciences, 17(9), 1440. MDPI. Accessed August 28, 2018, from http://www.mdpi.com/1422-0067/17/9/1440/htm

  3. Kothalawala, N., Mudalige, T. K., Sisco, P., & Linder, S. W. (2018). Novel analytical methods to assess the chemical and physical properties of liposomes. Journal of Chromatography B, 1091, 14–20.

    Article  CAS  Google Scholar 

  4. Bozzuto, G., & Molinari, A. (2015). Liposomes as nanomedical devices. International Journal of Nanomedicine, 975–999. https://doi.org/10.2147/ijn.s68861.

  5. Riaz, M., et al. (2018). Surface Functionalization and targeting strategies of liposomes in solid tumor therapy: A review. International Journal of Molecular Sciences, 19, 195.

    Article  Google Scholar 

  6. Sriraman, S. K., Aryasomayajula, B., & Torchilin, V. P. (2014). Barriers to drug delivery in solid tumors. Tissue Barriers, 2, e29528. https://doi.org/10.4161/tisb.29528.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Akbarzadeh, A., et al. (2013). Liposome: Classification, preparation, and applications. Nanoscale Research Letters, 8(1), 102. https://doi.org/10.1186/1556-276X-8-102. PMC. Web: August 22, 2018.

  8. Hofheinz, R. D., Gnad-Vogt, S. U., Beyer, U., & Hochhaus, A. (2005). Liposomal encapsulated anti-cancer drugs. Anti-Cancer Drugs, 16, 691–707. https://doi.org/10.1097/01.cad.0000167902.53039.5a.

    Article  CAS  PubMed  Google Scholar 

  9. Hatakeyama, H., Akita, H., & Harashima, H. (2013). The polyethyleneglycol dilemma: Advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors. Biological and Pharmaceutical Bulletin, 36, 892–899.

    Article  CAS  Google Scholar 

  10. Immordino, M. L., Dosio, F., & Cattel, L. (2006). Stealth liposomes: Review of the basic science, rationale, and clinical applications, existing and potential. International Journal of Nanomedicine, 1(3), 297–315. Print.

    Article  CAS  Google Scholar 

  11. Liu, X., Peng, H., & Wang, Q. (2014). Surface engineering of liposomal formulations for targeted drug delivery. Chemical Engineering and Process Techniques, 2(1), 1024.

    Google Scholar 

  12. Milla, P., Dosio, F., & Cattel, L. (2012). PEGylation of proteins and liposomes: A powerful and flexible strategy to improve the drug delivery. Current Drug Metabolism, 13, 105. https://doi.org/10.2174/138920012798356934.

    Article  CAS  Google Scholar 

  13. Shen, Z., Ye, H., Kröger, M., & Li, Y. (2018). Aggregation of polyethylene glycol polymers suppresses receptor-mediated endocytosis of PEGylated liposomes. Nanoscale, 10, 4545–4560.

    Article  CAS  Google Scholar 

  14. Fisher, R. K., et al. (2017). Improving the efficacy of liposome-mediated vascular gene therapy via lipid surface modifications. Journal of Surgical Research, 219, 136–144.

    Article  Google Scholar 

  15. Harris, J. M., Martin, N. E., & Modi, M. (2001). Pegylation: a novel process for modifying pharmacokinetics. Clinical Pharmacokinetics, 40(7), 539–551.

    Article  CAS  Google Scholar 

  16. Roberts, M. J., Bentley, M. D., & Harris, J. M. (2002). Chemistry for peptide and protein PEGylation. Advanced Drug Delivery Reviews, 54(4), 459–476.

    Article  CAS  Google Scholar 

  17. Suk, J. S., et al. (2016). PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews, 99(Pt A), 28–51. PMC. Web: August 23, 2018 from https://www.ncbi.nlm.nih.gov/pubmed/26456916

    Article  CAS  Google Scholar 

  18. Matsumura, Y., & Maeda, H. (1986). A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Research, 46, 6387–6392.

    CAS  PubMed  Google Scholar 

  19. Hobbs, S. K., et al. (1998). Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proceedings of the National Academy of Sciences of the United States of America, 95(8), 4607–4612. Print.

    Article  CAS  Google Scholar 

  20. Qi, R., Gao, Y., Tang, Y., He, R. R., Liu, T. L., He, Y., Sun, S., Li, B. Y., Li, Y. B., & Liu, G. (2009). PEG-conjugated PAMAM dendrimers mediate efficient intramuscular gene expression. The AAPS Journal, 11, 395–405.

    Article  CAS  Google Scholar 

  21. Jevprasesphant, R., Penny, J., Jalal, R., Attwood, D., McKeown, N. B., & D'Emanuele, A. (2003). The influence of surface modification on the cytotoxicity of PAMAM dendrimers. International Journal of Pharmaceutics, 252, 263–266. https://doi.org/10.1016/S0378-5173(02)00623-3.

    Article  CAS  PubMed  Google Scholar 

  22. Khutoryanskiy, V. V. (2018). Beyond PEGylation: Alternative surface-modification of nanoparticles with mucus-inert biomaterials. Advanced Drug Delivery Reviews, 124, 140–149.

    Article  CAS  Google Scholar 

  23. Sosnik, A., das Neves, J., & Sarmento, B. (2014). Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review. Progress in Polymer Science, 39, 2030–2075.

    Article  CAS  Google Scholar 

  24. Schneider, C. S., et al. (2017). Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Science Advances, 3, e1601556.

    Article  Google Scholar 

  25. Mert, O., et al. (2012). A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles. Journal of Controlled Release, 157, 455–460.

    Article  CAS  Google Scholar 

  26. Xu, Q. G., Boylan, N. J., Cai, S. T., Miao, B., Patel, H., & Hanes, J. (2013). Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus. Journal of Controlled Release, 170, 279–286.

    Article  CAS  Google Scholar 

  27. Guerrini, L., Alvarez-Puebla, R. A., & Pazos-Perez, N. (2018). Surface modifications of nanoparticles for stability in biological fluids. Materials, 11, 1154.

    Article  Google Scholar 

  28. Gref, R., Lück, M., Quellec, P., Marchand, M., Dellacherie, E., Harnisch, S., Blunk, T., & Müller, R. H. (2000). ‘Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): Influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids and Surfaces B: Biointerfaces, 18, 301–313.

    Article  CAS  Google Scholar 

  29. Thanh, N. T. K., & Green, L. A. W. (2010). Functionalization of nanoparticles for biomedical applications. Nano Today, 5, 213–230.

    Article  CAS  Google Scholar 

  30. Carril, M., Padro, D., Del Pino, P., Carrillo-Carrion, C., Gallego, M., & Parak, W. J. (2017). In situ detection of the protein corona in complex environments. Nature Communications, 8, 1542.

    Article  Google Scholar 

  31. Zhang, G., Yang, Z., Lu, W., Zhang, R., Huang, Q., Tian, M., Li, L., Liang, D., & Li, C. (2009). Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. Biomaterials, 30, 1928–1936.

    Article  CAS  Google Scholar 

  32. Rahme, K., Nolan, M. T., Doody, T., McGlacken, G. P., Morris, M. A., O’Driscoll, C., & Holmes, J. D. (2013). Highly stable pegylated gold nanoparticles in water: Applications in biology and catalysis. RSC Advances, 3, 21016–21024.

    Article  CAS  Google Scholar 

  33. Longmire, M., Choyke, P. L., & Kobayashi, H. (2008). Clearance properties of nano-sized particles and molecules as imaging agents: Considerations and caveats. Nanomedicine, 3, 703–717.

    Article  CAS  Google Scholar 

  34. Han, H.-S., et al. (2013). Spatial charge configuration regulates nanoparticle transport and binding behavior in vivo. Angewandte Chemie (International edition in English), 52(5), 1414–1419. PMC. Web: August 24, 2018.

    Google Scholar 

  35. Miteva, M., et al. (2015). Tuning PEGylation of mixed micelles to overcome intracellular and systemic siRNA delivery barriers. Biomaterials, 38, 97–107. PMC. Web: August 25, 2018.

    Article  CAS  Google Scholar 

  36. Mori, A., Klibanov, A. L., Torchilin, V. P., & Huang, L. (1991). Influence of the steric barrier activity of amphipathic poly(ethyleneglycol) and ganglioside GM1on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Letters, 284, 263–266.

    Article  CAS  Google Scholar 

  37. Gref, R., Domb, A., Quellec, P., et al. (1995). The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. Advanced Drug Delivery Reviews, 16, 215–233.

    Article  CAS  Google Scholar 

  38. Owensiii, D., & Peppas, N. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307, 93–102.

    Article  Google Scholar 

  39. He, Q., Zhang, J., Shi, J., Zhu, Z., Zhang, L., Bu, W., Guo, L., & Chen, Y. (2010). The effect of PEGylation of mesoporous silica nanoparticles on nonspecific binding of serum proteins and cellular responses. Biomaterials, 31, 1085–1092.

    Article  CAS  Google Scholar 

  40. Yang, Q., Jones, S. W., Parker, C. L., Zamboni, W. C., Bear, J. E., & Lai, S. K. (2014). Evading immune cell uptake and clearance requires PEG grafting at densities substantially exceeding the minimum for brush conformation. Molecular Pharmaceutics, 11, 1250–1258.

    Article  CAS  Google Scholar 

  41. Eloy, J. O., et al. (2014). Liposomes as carriers of hydrophilic small molecule drugs: Strategies to enhance encapsulation and delivery. Colloids and Surfaces B: Biointerfaces, 123, 345–363.

    Article  CAS  Google Scholar 

  42. Kajimoto, K., Katsumi, T., Nakamura, T., Kataoka, M., & Harashima, H. (2018). Liposome microencapsulation for the surface modification and improved entrapment of cytochrome c for targeted delivery. Journal of the American Oil Chemists Society, 95, 101–109.

    Article  CAS  Google Scholar 

  43. Nag, O. K., & Awasthi, V. (2013). Surface engineering of liposomes for stealth behavior. Pharmaceutics, 5(4), 542–569. PMC. Web: August 27, 2018.

    Google Scholar 

  44. Tirosh, O., et al. (1998). Hydration of polyethylene glycol-grafted liposomes. Biophysical Journal, 74(3), 1371–1379.

    Article  CAS  Google Scholar 

  45. Lehtonen, J. Y., & Kinnunen, P. K. (1995). Poly(ethylene Glycol)-induced and temperature-dependent phase separation in fluid binary phospholipid membranes. Biophysical Journal, 68(2), 525–535. PMC. Web: August 27, 2018.

    Google Scholar 

  46. Stark, B., Pabst, G., & Prassl, R. (2010). Long-term stability of sterically stabilized liposomes by freezing and freeze-drying: Effects of cryoprotectants on structure. European Journal of Pharmaceutical Sciences, 41, 546–555. https://doi.org/10.1016/j.ejps.2010.08.010.

    Article  CAS  PubMed  Google Scholar 

  47. Szebeni, J. (2005). Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicity. Toxicology, 216, 106–121. https://doi.org/10.1016/j.tox.2005.07.023.

    Article  CAS  PubMed  Google Scholar 

  48. Neun, B., Barenholz, Y., Szebeni, J., & Dobrovolskaia, M. (2018). Understanding the role of anti-PEG antibodies in the complement activation by doxil in vitro. Molecules, 23, 1700.

    Article  Google Scholar 

  49. Szebeni, J., Alving, C. R., Rosivall, L., Bunger, R., Baranyi, L., Bedocs, P., Toth, M., & Barenholz, Y. (2007). Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles. Journal of Liposome Research, 17, 107–117.

    Article  CAS  Google Scholar 

  50. Chen, B. M., Su, Y. C., Chang, C. J., Burnouf, P. A., Chuang, K. H., Chen, C. H., Cheng, T. L., Chen, Y. T., Wu, J. Y., & Roffler, S. R. (2016). Measurement of pre-existing IgG and IgM antibodies against polyethylene glycol in healthy individuals. Analytical Chemistry, 88, 10661–10666.

    Article  CAS  Google Scholar 

  51. Yang, Q., Ma, Y., Zhao, Y., She, Z., Wang, L., Li, J., Wang, C., & Deng, Y. (2013). Accelerated drug release and clearance of pegylated epirubicin liposomes following repeated injections: A new challenge for sequential low-dose chemotherapy. International Journal of Nanomedicine, 8, 1257–1268.

    PubMed  PubMed Central  Google Scholar 

  52. Nag, O. K., Yadav, V. R., Hedrick, A., & Awasthi, V. (2013). Post-modification of preformed liposomes with novel non-phospholipid poly(ethylene glycol)-conjugated hexadecylcarbamoylmethyl hexadecanoic acid for enhanced circulation persistence in vivo. International Journal of Pharmaceutics, 446, 119–129. https://doi.org/10.1016/j.ijpharm.2013.02.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gabizon, A., Goren, D., Horowitz, A. T., Tzemach, D., Lossos, A., & Siegal, T. (1997). Long-circulating liposomes for drug delivery in cancer therapy: A review of biodistribution studies in tumor-bearing animals. Advanced Drug Delivery Reviews, 24, 337–344. https://doi.org/10.1016/S0169-409X(96)00476-0.

    Article  CAS  Google Scholar 

  54. Cui, J., Li, C., Guo, W., Li, Y., Wang, C., Zhang, L., Zhang, L., Hao, Y., & Wang, Y. (2007). Direct comparison of two pegylated liposomal doxorubicin formulations: Is auc predictive for toxicity and efficacy? Journal of Controlled Release, 118, 204–215. https://doi.org/10.1016/j.jconrel.2006.12.002.

    Article  CAS  PubMed  Google Scholar 

  55. Yamada, A., Taniguchi, Y., Kawano, K., Honda, T., Hattori, Y., & Maitani, Y. (2008). Design of folate-linked liposomal doxorubicin to its antitumor effect in mice. Clinical Cancer Research, 14(24), 8161–8168.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia

    Doniya Milani & Umi Athiyah

  2. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Dewi Melani Hariyadi & Yashwant V Pathak

  3. Adjunct professor at Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia

    Yashwant V Pathak

  4. Faculty of Public Health, Airlangga University, Surabaya, Indonesia

    Dewi Melani Hariyadi

Authors
  1. Doniya Milani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Umi Athiyah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dewi Melani Hariyadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yashwant V Pathak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yashwant V Pathak .

Editor information

Editors and Affiliations

  1. College of Pharmacy, University of South Florida, Tampa, FL, USA

    Yashwant V Pathak

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Milani, D., Athiyah, U., Hariyadi, D.M., Pathak, Y.V. (2019). Surface Modifications of Liposomes for Drug Targeting. In: Pathak, Y. (eds) Surface Modification of Nanoparticles for Targeted Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-030-06115-9_11

Download citation

Publish with us

Policies and ethics

Search

Navigation