Skip to main content

Advertisement

SpringerLink
Log in

Potential chitosan-coated alginate nanoparticles for ocular delivery of daptomycin

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Daptomycin may offer an antibacterial alternative for the treatment of endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and other potential agents. In the present project, mucoadhesive chitosan-coated alginate (CS-ALG) nanoparticles are proposed as an effective delivery system for daptomycin permeation across ocular epithelia, with potential for the treatment of bacterial endophthalmitis. CS-ALG nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation, and characterized regarding particle size, polydispersity, and zeta potential. The encapsulation efficiency was determined and antimicrobial activity was also tested after encapsulation of the antibiotic. Also, in vitro ocular permeability of free daptomycin and encapsulation into chitosan and CS-ALG nanoparticles was evaluated using ocular epithelial cell culture models. Formulated daptomycin-loaded CS-ALG nanoparticles were negatively charged, with a size range of 380–420 nm, suitable for ocular application. The encapsulation efficiency was between 79 and 92 %, with decreasing alginate:daptomycin mass ratios. The antibacterial activity of daptomycin against major microorganisms responsible for bacterial endophthalmitis was not affected by encapsulation into nanoparticles. Daptomycin permeability was up to 16 % (chitosan nanoparticles) and 9 % (CS-ALG nanoparticles) through corneal cell monolayer, and 18 % (chitosan nanoparticles) and 12 % (CS-ALG nanoparticles) for retinal cell monolayer after 4 h, demonstrating epithelial retention of the drug compared to free drug. The developed daptomycin-loaded CS-ALG nanoparticles seem to be an interesting and potential system for ocular daptomycin delivery and treatment of bacterial endophthalmitis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Callegan MC, Engelbert M, Parke DW 2nd, Jett BD, Gilmore MS (2002) Bacterial endophthalmitis: epidemiology, therapeutics, and bacterium–host interactions. Clin Microbiol Rev 15:111–124

    Article  PubMed Central  PubMed  Google Scholar 

  2. Kunimoto DY, Das T, Sharma S, Jalali S, Majji AB, Gopinathan U, Athmanathan S, Rao TN (1999) Microbiologic spectrum and susceptibility of isolates: part I. Postoperative endophthalmitis. Endophthalmitis Research Group. Am J Ophthalmol 128:240–242

    Article  CAS  PubMed  Google Scholar 

  3. Callegan MC, Gilmore MS, Gregory M, Ramadan RT, Wiskur BJ, Moyer AL, Hunt JJ, Novosad BD (2007) Bacterial endophthalmitis: therapeutic challenges and host–pathogen interactions. Prog Retin Eye Res 26:189–203

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Jeu L, Fung HB (2004) Daptomycin: a cyclic lipopeptide antimicrobial agent. Clin Ther 26:1728–1757

    Article  CAS  PubMed  Google Scholar 

  5. Enoch DA, Bygott JM, Daly ML, Karas JA (2007) Daptomycin. J Infect 55:205–213

    Article  PubMed  Google Scholar 

  6. Urtti A (2006) Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58:1131–1135

    Article  CAS  PubMed  Google Scholar 

  7. de la Fuente M, Raviña M, Paolicelli P, Sanchez A, Seijo B, Alonso MJ (2010) Chitosan-based nanostructures: a delivery platform for ocular therapeutics. Adv Drug Deliv Rev 62:100–117

    Article  PubMed  Google Scholar 

  8. Silva NC, Silva S, Sarmento B, Pintado M (2013) Chitosan nanoparticles for daptomycin delivery in ocular treatment of bacterial endophthalmitis. Drug Deliv ID:858195. doi:10.3109/10717544.2013.858195

  9. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK (2008) Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimisation and in vitro characterisation. Eur J Pharm Biopharm 68:513–525

    CAS  PubMed  Google Scholar 

  10. Nagarwal RC, Kumar R, Pandit JK (2012) Chitosan coated sodium alginate–chitosan nanoparticles loaded with 5-FU for ocular delivery: in vitro characterization and in vivo study in rabbit eye. Eur J Pharm Sci 47:678–685

    Article  CAS  PubMed  Google Scholar 

  11. Yan XL, Khor E, Lim LY (2001) Chitosan–alginate films prepared with chitosans of different molecular weights. J Biomed Mater Res 58:358–365

    Article  CAS  PubMed  Google Scholar 

  12. de Campos AM, Diebold Y, Carvalho ELS, Sánchez A, Alonso MJ (2004) Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity. Pharm Res 21:803–810

    Article  PubMed  Google Scholar 

  13. Liu W, Griffith M, Li F (2008) Alginate microsphere–collagen composite hydrogel for ocular drug delivery and implantation. J Mater Sci Mater Med 19:3365–3371

    Article  CAS  PubMed  Google Scholar 

  14. Liu S, Jones L, Gu FX (2012) Nanomaterials for ocular drug delivery. Macromol Biosci 12:608–620

    Article  CAS  PubMed  Google Scholar 

  15. Sangeetha S, Venkatesh DN, Adhiyaman R, Santhi K, Suresh B (2007) Formulation of sodium alginate nanospheres containing amphotericin B for the treatment of systemic candidiasis. Trop J Pharm Res 6:653–659

    Article  Google Scholar 

  16. Ding S (1998) Recent developments in ophthalmic drug delivery. Pharm Sci Technol Today 1:328–335

    Article  CAS  Google Scholar 

  17. Nagarwal RC, Kant S, Singh PN, Maiti P, Pandit JK (2009) Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J Control Release 136:2–13

    Article  CAS  PubMed  Google Scholar 

  18. Mi FL, Tan YC, Liang HF, Sung HW (2002) In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. Biomaterials 23:181–191

    Article  CAS  PubMed  Google Scholar 

  19. Tamboli V, Mishra GP, Mitra AK (2012) Biodegradable polymers for ocular drug delivery. Adv Ocul Drug Deliv 2012:65–86

    Google Scholar 

  20. Severino P, Vasconcellos FC, Figueiredo ES (2007) Uso tópico de quitosana em oftalmologia. Rev Bras Farm 88:155–158

    CAS  Google Scholar 

  21. Mourya VK, Inamdar NN (2008) Chitosan-modifications and applications: opportunities galore. React Funct Polym 68:1013–1051

    Article  CAS  Google Scholar 

  22. Subramanian A, Vasanthan KS, Krishnan UM, Sethuraman S (2011) Chitosan and its derivatives in clinical use and applications. In: Domb AJ, Kumar N, Ezra A (eds) Biodegradable polymers in clinical use and clinical development. Wiley, New Jersey, pp 113–135

    Google Scholar 

  23. Zahoor A, Sharma S, Khuller GK (2005) Inhalable alginate nanoparticles as antitubercular drug carriers against experimental tuberculosis. Int J Antimicrob Agents 26:298–303

  24. Sarmento B, Ribeiro A, Veiga F, Ferreira D (2006) Development and validation of a rapid reversed-phase HPLC method for the determination of insulin from nanoparticulate systems. Biomed Chromatogr 20:898–903

    Article  CAS  PubMed  Google Scholar 

  25. Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D (2007) Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm Res 24:2198–2206

    Article  CAS  PubMed  Google Scholar 

  26. Clinical and Laboratory Standards Institute (CLSI) (2003) Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically, NCCLS document M7-A6, 6th edition. Villanova, Pennsylvania, USA

  27. Clinical and Laboratory Standards Institute (CLSI) (2005) Performance standards for antimicrobial susceptibility testing, 15th informational supplement, NCCLS document M100-S15. Villanova, Pennsylvania, USA

  28. Dunn KC, Aotaki-Keen AE, Putkey FR, Hjelmeland LM (1996) ARPE-19, a human retinal pigment epithelial cell line with differentiated properties. Exp Eye Res 62:155–169

    Article  CAS  PubMed  Google Scholar 

  29. Barar J, Asadi M, Mortazavi-Tabatabaei SA, Omidi Y (2009) Ocular drug delivery impact of in vitro cell culture models. J Ophthalmic Vis Res 4:238–252

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Geiger RC, Waters CM, Kamp DW, Glucksberg MR (2005) KGF prevents oxygen-mediated damage in ARPE-19 cells. Invest Ophthalmol Vis Sci 46:3435–3442

    Article  PubMed  Google Scholar 

  31. Zimmer A, Kreuter J (1995) Microspheres and nanoparticles used in ocular delivery systems. Adv Drug Deliv Rev 16:61–73

    Article  CAS  Google Scholar 

  32. Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327

    Article  CAS  Google Scholar 

  33. Chen A, Haddad D, Wang R (2009) Analysis of chitosan-alginate bone scaffolds. Rutgers University, New Jersey Governor’s School of Engineering & Technology

  34. Harnsilawat T, Pongsawatmanit R, McClements DJ (2006) Characterization of β-lactoglobulin–sodium alginate interactions in aqueous solutions: a calorimetry, light scattering, electrophoretic mobility and solubility study. Food Hydrocoll 20:577–585

    Article  CAS  Google Scholar 

  35. Nagpal K, Singh SK, Mishra DN (2010) Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull (Tokyo) 58:1423–1430

    Article  CAS  Google Scholar 

  36. Barry AL, Fuchs PC, Brown SD (2001) In vitro activities of daptomycin against 2,789 clinical isolates from 11 North American medical centers. Antimicrob Agents Chemother 45:1919–1922

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Fuchs PC, Barry AL, Brown SD (2002) In vitro bactericidal activity of daptomycin against staphylococci. J Antimicrob Chemother 49:467–470

    Article  CAS  PubMed  Google Scholar 

  38. Fluit AC, Schmitz FJ, Verhoef J, Milatovic D (2004) In vitro activity of daptomycin against gram-positive European clinical isolates with defined resistance determinants. Antimicrob Agents Chemother 48:1007–1011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Hornof M, Toropainen E, Urtti A (2005) Cell culture models of the ocular barriers. Eur J Pharm Biopharm 60:207–225

    Article  CAS  PubMed  Google Scholar 

  40. Mannermaa E, Reinisalo M, Ranta V-P, Vellonen K-S, Kokki H, Saarikko A, Kaarniranta K, Urtti A (2010) Filter-cultured ARPE-19 cells as outer blood–retinal barrier model. Eur J Pharm Sci 40:289–296

    Article  CAS  PubMed  Google Scholar 

  41. Nagai N, Ito Y, Okamoto N, Shimomura Y (2014) A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability. Toxicology 319:53–62

    Article  CAS  PubMed  Google Scholar 

  42. Antunes F, Andrade F, Araújo F, Ferreira D, Sarmento B (2013) Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs. Eur J Pharm Biopharm 83:427–435

    Article  CAS  PubMed  Google Scholar 

  43. Diebold Y, Calonge M (2010) Applications of nanoparticles in ophthalmology. Prog Retin Eye Res 29:596–609

    Article  CAS  PubMed  Google Scholar 

  44. De Campos AM, Sánchez A, Alonso MJ (2001) Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224:159–168

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Funds from FCT through project PEst-OE/EQB/LA0016/2013. The authors would like to thank Cubist Pharmaceuticals, Inc. and Novartis Pharma AG for providing the daptomycin.

Conflict of interest

The authors report no conflict of interests.

Author information

Authors and Affiliations

  1. CBQF - Centre for Biotechnology and Fine Chemistry - State Associated Laboratory, College of Biotechnology, Catholic University of Portugal/ Porto, Rua Arquiteto Lobão Vital, Apartado 2511, 4200-401, Porto, Portugal

    J. R. Costa, N. C. Silva & M. Pintado

  2. CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Rua Central de Gandra, 1317, 4585-116, Gandra, PRD, Portugal

    B. Sarmento

  3. INEB—Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal

    B. Sarmento

Authors
  1. J. R. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. C. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Sarmento
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Pintado
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Pintado.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa, J., Silva, N.C., Sarmento, B. et al. Potential chitosan-coated alginate nanoparticles for ocular delivery of daptomycin. Eur J Clin Microbiol Infect Dis 34, 1255–1262 (2015). https://doi.org/10.1007/s10096-015-2344-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-015-2344-7

Keywords

Search

Navigation