Skip to main content
SpringerLink
Log in

Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs. Surface modified NPs (MOX-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetic and in vivo biodistribution following oral administration were investigated. NP surface charge was closed to neutral +4.76 mV and significantly affected by the WSC coating. MOX-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long-drawn-out the blood circulation half-life with resultant reduced liver sequestration vis-à-vis MOX-PLGA NPs. The studies, therefore, indicate the successful formulation development of MOX-PEG-WSC NPs that showed sustained release behavior from nanoparticles which indicates low frequency of dosing.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

REFERENCES

  1. Mustafa S, Pai RS, Singh G, Devi VK. Nanocarrier-based interventions for the management of MDR/XDR-TB. J Drug Target. 2015;23:287–304.

    Article  CAS  PubMed  Google Scholar 

  2. Nuermberger EL, Yoshimatsu T, Tyagi S, et al. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med. 2004;170:1131–4.

    Article  PubMed  Google Scholar 

  3. Mitchison DA. Drug resistance in tuberculosis. Eur Respir J. 2005;25:376–9.

    Article  CAS  PubMed  Google Scholar 

  4. Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J. 2011;13:519–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Soto S, Roses L, Avila S, et al. Moxifloxacin-induced acute liver injury. Am J Gastroenterol. 2002;97:1853–4.

    Article  PubMed  Google Scholar 

  6. Verma R, Dhamija R, Batts DH, et al. Moxifloxacin induced fatal hepatotoxicity in a 72-year-old man: a case report. Cases J. 2009;2:8063.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Govender T, Stolnik S, Garnett MC, et al. PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug. J Control Release. 1999;57:171–85.

    Article  CAS  PubMed  Google Scholar 

  8. Kisich KO, Gelperina S, Higgins MP, et al. Encapsulation of moxifloxacin within poly(butyl cyanoacrylate) nanoparticles enhances efficacy against intracellular Mycobacterium tuberculosis. Int J Pharm. 2007;345:154–62.

    Article  CAS  PubMed  Google Scholar 

  9. Gadad A, Chandra PS, Dandagi P, et al. Moxifloxacin loaded polymeric nanoparticles for sustained ocular drug delivery. Int J Pharm Sci Nanotech. 2012;5:1727–34.

    Google Scholar 

  10. Turk CTS, Oz UC, Serim TM, et al. Formulation and optimization of nonionic surfactants emulsified nimesulide-loaded PLGA-based nanoparticles by design of experiments. AAPS Pharm SciTech. 2014;15:161–76.

    Article  CAS  Google Scholar 

  11. Suñer J, Calpena AC, Clares B, et al. Development of clotrimazole multiple W/O/W emulsions as vehicles for drug delivery: effects of additives on emulsion stability. AAPS Pharm Sci Tech. 2016. doi:10.1208/s12249-016-0529-8.

    Google Scholar 

  12. Singh G, Pai RS. Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential. Expert Opin Drug Deliv. 2014;11:1023–32.

    Article  CAS  PubMed  Google Scholar 

  13. Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307:93–102.

    Article  CAS  PubMed  Google Scholar 

  14. Vassiliou AA, Papadimitriou SA, Bikiaris DN, et al. Facile synthesis of polyester-PEG triblock copolymers and preparation of amphiphilic nanoparticles as drug carriers. J Control Release. 2010;148:388–95.

    Article  CAS  PubMed  Google Scholar 

  15. Dunn SE, Coombes AGA, Garnett MC, et al. In vitro cell interaction and in vivo biodistribution of poly(lactide-co-glycolide) nanospheres surface modified by poloxamer and poloxamine copolymers. J Control Release. 1997;44:65–76.

    Article  CAS  Google Scholar 

  16. Semete B, Booysen L, Kalombo L, et al. Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration. Int J Pharm. 2012;424:115–20.

    Article  CAS  PubMed  Google Scholar 

  17. Esmaeili F, Ghahremani MH, Esmaeili B, et al. PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution. Int J Pharm. 2008;349:249–55.

    Article  CAS  PubMed  Google Scholar 

  18. Lemarchand C, Gref R, Couvreur P. Polysaccharide-decorated nanoparticles. Eur J Pharm Biopharm. 2004;58:327–41.

    Article  CAS  PubMed  Google Scholar 

  19. Jaulin N, Appel M, Passirani C, et al. Reduction of the uptake by a macrophagic cell line of nanoparticles bearing heparin or dextran covalently bound to poly(methyl methacrylate). J Drug Target. 2000;8:165–72.

    Article  CAS  PubMed  Google Scholar 

  20. Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res. 1998;15:1326–31.

    Article  CAS  PubMed  Google Scholar 

  21. Djurdjevic AL, Stankov MJ, Djurdjevic P. Optimization and validation of the direct HPLC method for the determination of moxifloxacin in plasma. J Chromatogr B. 2006;844:104–11.

    Article  Google Scholar 

  22. Qian X, Dong H, Hu X, et al. Analysis of the interferences in quantitation of a site-specifically PEGylated exendin-4 analog by the Bradford method. Anal Biochem. 2014;465:50–2.

    Article  CAS  PubMed  Google Scholar 

  23. Raju B, Ramesh M, Roshan M, et al. Development and validation of liquid chromatography-mass spectrometric method for simultaneous determination of moxifloxacin and ketorolac in rat plasma: application to pharmacokinetic study. Biomed Chromatogr. 2012;26:1341–7.

    Article  CAS  PubMed  Google Scholar 

  24. Moghimi SM, Szebeni J. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res. 2003;42:463–78.

    Article  CAS  PubMed  Google Scholar 

  25. Sheng Y, Liu C, Yuan Y, et al. Long circulating polymeric nanoparticles bearing a combinatorial coating of PEG and water soluble chitosan. Biomaterials. 2009;30:2340–8.

    Article  CAS  PubMed  Google Scholar 

  26. Wang J, Liu CS, Chi P. Aggregate formation and surface activity of partially deacetylated water-soluble chitin. Res Chem Intermed. 2008;34:169–79.

    Article  CAS  Google Scholar 

  27. Norris DA, Puri N, Sinko PJ. The effect of physical barriers and properties on the oral absorption of particulates. Adv Drug Deliv Rev. 1998;34:135–54.

    Article  CAS  PubMed  Google Scholar 

  28. Cui G, Wang L, Davis PJ. Preparation and physical characterization of a novel marine oil emulsion as a potential new formulation vehicle for lipid soluble drugs. Int J Pharm. 2006;325:180–5.

    Article  CAS  PubMed  Google Scholar 

  29. Takeuchi H, Thongborisute J, Matsui Y. Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems. Adv Drug Deliv Rev. 2005;57:1583–94.

    Article  CAS  PubMed  Google Scholar 

  30. Bhandari R, Kaur IP. Pharmacokinetics, tissue distribution and relative bioavailability of isoniazid-solid lipid nanoparticles. Int J Pharm. 2012;441:202–12.

    Article  PubMed  Google Scholar 

  31. Muller RH, Wallis KH, Troster SD, et al. In vitro characterization of poly (methyl-methacrylate) nanoparticles and correlation to their in vivo fate. J Control Release. 1992;20:237–46.

    Article  Google Scholar 

  32. Jaiswal J, Gupta SK, Kreuter J. Preparation of biodegradable cyclosporine nanoparticles by high-pressure emulsification-solvent evaporation process. J Controlled Release. 2004;96:169–78.

    Article  CAS  Google Scholar 

  33. Panagi Z, Beletsi A, Evangelatos G, et al. Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles. Int J Pharm. 2001;221:143–52.

    Article  CAS  PubMed  Google Scholar 

  34. Mittal G, Sahana DK, Bhardwaj V, et al. Estradiol loaded PLGA nanoparticles for oral administration: effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo. J Control Release. 2007;119:77–85.

    Article  CAS  PubMed  Google Scholar 

  35. Mao S, Xu J, Cai C, Kissel T, et al. Effect of WOW process parameters on morphology and burst release of FITC-dextran loaded PLGA microspheres. Int J Pharm. 2007;334:137–48.

    Article  CAS  PubMed  Google Scholar 

  36. Zhang Z, Lee SH, Feng SS. Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for targeted drug delivery. Biomaterials. 2007;28:1889–99.

    Article  PubMed  Google Scholar 

  37. Mu FSS. A novel controlled release formulation for anticancer drug paclitaxel (Taxols): PLGA nanoparticles containing vitamin E TPGS. J Control Release. 2003;86:33–48.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Shobha Rani R. H, principal of Al-Ameen College of Pharmacy for her advice and support to carry out this research work. The authors are gratefully grateful to Cipla private Ltd, Sikkim, India for providing the gift sample of moxifloxacin. We are also grateful to M/s Boehringer Ingelheim Pharma GmbH & Co. KG (Binger Street, Ingelheim, Germany) for providing the gift sample of PLGA.

Author information

Authors and Affiliations

  1. Pharmaceutics Division, Faculty of Pharmacy, Al-Ameen College of Pharmacy, Near Lal Bagh Main gate, Hosur Road, Bangalore, Karnataka, 560027, India

    Sanaul Mustafa, V. Kusum Devi & Roopa S Pai

Authors
  1. Sanaul Mustafa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Kusum Devi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roopa S Pai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Kusum Devi.

Ethics declarations

All animal investigations were performed as per requisite protocol approved by the Institutional Animal Ethics Committee [Letter No. AACP/IAEC/Jun-2014-01]. The committee is duly approved for the purpose of control and supervision of experiments on the animals by the government of India.

Conflict of interest

The authors declare that they have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mustafa, S., Devi, V.K. & Pai, R.S. Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles. Drug Deliv. and Transl. Res. 7, 27–36 (2017). https://doi.org/10.1007/s13346-016-0326-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-016-0326-7

Keywords

Search

Navigation