Skip to main content

Advertisement

SpringerLink
Log in

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin.

Methods

Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used.

Results

The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from −19 to −13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well.

Conclusion

The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

COX enzyme:

Cyclooxygenase enzyme

CLSM:

Confocal laser scanning microscopy

DSC:

Differential scanning calorimeter

EE:

Encapsulation efficiency

FTIR:

Fourier transform infrared spectroscopy

IND:

Indomethacin

NPs:

Nanoparticles

NSAIDs:

Non-Steroidal Anti-inflammatory Drugs

PCL:

Polycaprolactone

PVA:

Polyvinyl alcohol

RT:

Room temperature (25°C)

SEM:

Scanning Electron Microscopy

TEM:

Transmission Electron Microscopy

References

  1. Cordero JA, Camacho M, Obach R, Domenech J, Vila L. In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs. Eur J Pharm Biopharm. 2001;51:135–42.

    Article  CAS  PubMed  Google Scholar 

  2. Sostres C, Gargallo CJ, Arroyo MT, Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24:121–32.

    Article  CAS  PubMed  Google Scholar 

  3. Bateman DN. Non-steroidal anti-inflammatory drugs. Medicine (Baltimore). 2012;40:140.

    Article  Google Scholar 

  4. Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Surv Ophthalmol. 2010;55:108–33.

    Article  PubMed  Google Scholar 

  5. Ziltener J-L, Leal S, Fournier P-E. Non-steroidal anti-inflammatory drugs for athletes: an update. Ann Phys Rehabil Med. 2010;53:278–82. 282–8

    Article  PubMed  Google Scholar 

  6. Závišová V, Koneracká M, Štrbák O, Tomašovičová N, Kopčanský P, Timko M, et al. Encapsulation of indomethacin in magnetic biodegradable polymer nanoparticles. J Magn Magn Mater. 2007;311:379–82.

    Article  Google Scholar 

  7. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26:1261–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tomoda K, Terashima H, Suzuki K, Inagi T, Terada H, Makino K. Enhanced transdermal delivery of indomethacin using combination of PLGA nanoparticles and iontophoresis in vivo. Colloids Surf B: Biointerfaces. 2012;92:50–4.

    Article  CAS  PubMed  Google Scholar 

  9. Suksiriworapong J, Sripha K, Kreuter J, Junyaprasert VB. Comparative study of Ibuprofen and Indomethacin loaded poly (caprolactone) nanoparticles: physicochemical properties. J Magn Magn Mater. 2010;37:17–27.

    CAS  Google Scholar 

  10. Iqbal M, Zafar N, Fessi H, Elaissari A. Double emulsion solvent evaporation techniques used for drug encapsulation. Int J Pharm. 2015;496:173–90.

    Article  CAS  PubMed  Google Scholar 

  11. Jelvehgari M, Montazam SH. Comparison of Microencapsulation by Emulsion-Solvent Extraction/Evaporation Technique Using Derivatives Cellulose and Acrylate-Methacrylate Copolymer as Carriers. Jundishapur J Nat Pharm Prod. 2012;7:144–52.

    PubMed  PubMed Central  Google Scholar 

  12. Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989;55:R1–4.

    Article  CAS  Google Scholar 

  13. Miladi K, Sfar S, Fessi H, Elaissari A. Nanoprecipitation process: from particle preparation to in vivo applications. Polymer Nanoparticles for Nanomedicines 2016. p. 17–53.

  14. Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. Int J Pharm. 2010;385:113–42.

    Article  CAS  PubMed  Google Scholar 

  15. Park J-H, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J Control Release Off J Control Release Soc. 2005;104:51–66.

    Article  CAS  Google Scholar 

  16. Dash TK, Konkimalla VB. Poly-є-caprolactone based formulations for drug delivery and tissue engineering: A review. J Control Release Off. 2012;158:15–33.

    Article  CAS  Google Scholar 

  17. Badri W, Miladi K, Nazari QA, Fessi H, Elaissari A. Effect of process and formulation parameters on polycaprolactone nanoparticles prepared by solvent displacement. Colloids Surf A Physicochem Eng Asp. 2017;516:238–44.

    Article  CAS  Google Scholar 

  18. Pygall SR, Whetstone J, Timmins P, Melia CD. Pharmaceutical applications of confocal laser scanning microscopy: The physical characterisation of pharmaceutical systems. Adv Drug Deliv Rev. 2007;59:1434–52.

    Article  CAS  PubMed  Google Scholar 

  19. Alvarez-Román R, Naik A, Kalia YN, Guy RH, Fessi H. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99:53–62.

    Article  PubMed  Google Scholar 

  20. Zhang X, Zhang X, Wang S, Liu M, Tao L, Wei Y. Surfactant modification of aggregation-induced emission material as biocompatible nanoparticles: Facile preparation and cell imaging. Nanoscale. 2012;5:147–50.

    Article  PubMed  Google Scholar 

  21. Adibkia K, Javadzadeh Y, Dastmalchi S, Mohammadi G, Niri FK, Alaei-Beirami M. Naproxen-eudragit RS100 nanoparticles: preparation and physicochemical characterization. Colloids Surf B: Biointerfaces. 2011;83:155–9.

    Article  CAS  PubMed  Google Scholar 

  22. Gratieri T, Schaefer UF, Jing L, Gao M, Kostka K-H, Lopez RFV, et al. Penetration of quantum dot particles through human skin. J Biomed Nanotechnol. 2010;6:586–95.

    Article  CAS  PubMed  Google Scholar 

  23. Vulovic N, Primorac M, Stupar M, Ford JL. Some studies into the properties of indomethacin suspensions intended for ophthalmic use. Int J Pharm. 1989;55:123–8.

    Article  CAS  Google Scholar 

  24. Gupta KC, Haider A, Choi Y, Kang I. Nanofibrous scaffolds in biomedical applications. Biomater Res. 2014;18:5.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Braz WR, Rocha NL, de Faria EH, Silva MLAE, Ciuffi KJ, Tavares DC, et al. Incorporation of anti-inflammatory agent into mesoporous silica. Nanotechnology. 2016;27(38):385,103.

    Article  Google Scholar 

  26. Elzein T, Nasser-Eddine M, Delaite C, Bistac S, Dumas P. FTIR study of polycaprolactone chain organization at interfaces. J Colloid Interface Sci. 2004;273:381–7.

    Article  CAS  PubMed  Google Scholar 

  27. Lin H-L, Zhang G-C, Lin S-Y. Real-time co-crystal screening and formation between indomethacin and saccharin via DSC analytical technique or DSC–FTIR microspectroscopy. J Therm Anal Calorim. 2015;120:679–87.

    Article  CAS  Google Scholar 

  28. Tomoda K, Terashima H, Suzuki K, Inagi T, Terada H, Makino K. Enhanced transdermal delivery of indomethacin-loaded PLGA nanoparticles by iontophoresis. Colloids Surf B: Biointerfaces. 2011;88:706–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments and Disclosures

Waisudin Badri gratefully acknowledges French foreign affairs ministry and Afghanistan higher education ministry for providing the PhD scholarship.

Author information

Authors and Affiliations

  1. Univ Lyon, University Claude Bernard Lyon-1, CNRS, LAGEP UMR 5007, 43 boulevard du 11 novembre 1918, F-69100,, Villeurbanne, France

    Waisudin Badri, Karim Miladi, Géraldine Agusti, Hatem Fessi & Abdelhamid Elaissari

  2. Faculty of Pharmacy, Kabul University, Kabul, Afghanistan

    Waisudin Badri & Qand Agha Nazari

  3. Laboratory of Engineering and Cutaneous Biology, UMR 1098, Bourgogne Franche-Comté University, 19 rue Ambroise Paré, 25000, Besançon, France

    Sophie Robin & Céline Viennet

Authors
  1. Waisudin Badri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karim Miladi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie Robin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Céline Viennet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qand Agha Nazari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Géraldine Agusti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hatem Fessi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Abdelhamid Elaissari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abdelhamid Elaissari.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Badri, W., Miladi, K., Robin, S. et al. Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study. Pharm Res 34, 1773–1783 (2017). https://doi.org/10.1007/s11095-017-2166-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-017-2166-7

KEY WORDS

Search

Navigation