Skip to main content

Advertisement

Log in

A Fluorescence Study of the Interaction of Anticancer Drug Molecule Doxorubicin Hydrochloride in Pluronic P123 and F127 Micelles

  • ORIGINAL ARTICLE
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer treatment. The use of polymers such as Pluronic is being studied widely for the formulation of doxorubicin hydrochloride. However, the basic understanding of the physicochemical properties of pluronic micelles in presence of doxorubicin hydrochloride is a very essential topic of study. Doxorubicin hydrochloride is fluorescent; this helped us to study its sensitivity towards the Pluronic microenvironment using the fluorescence technique. In this work, the interaction and place of location of doxorubicin hydrochloride in Pluronic F127 and P123 micelles has been studied extensively using steady-state fluorescence intensity, dynamic fluorescence lifetime, quenching studies, dynamic light scattering, and zeta potential measurements, at different Pluronic concentrations. Using a fluorescence quenching experiment, doxorubicin hydrochloride was found to reside near the hydrophilic PEO corona region of the Pluronic micelles. For both the Pluronic, in the concentration range of study, the micellar size was found to be below 30 nm; this may have a greater advantage for various applications.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Barret PC, Gustavsson T, Markovitsi D, Manet I, Monti S (2013) Unravelling molecular mechanisms in the fluorescence spectra of doxorubicin in aqueous solution by femtosecond fluorescence spectroscopy. Phys Chem Chem Phys 15:2937–2944

    Google Scholar 

  2. Karukstis KK, Thompson EHZ, Whiles JA, Rosenfeld RJ (1998) Deciphering the fluorescence signature of daunomycin and doxorubicin. Biophys Chem 73:249–263

    CAS  PubMed  Google Scholar 

  3. Chen N, Wu C, Chung C, Hwu Y, Cheng S, Mou C, Lo L (2012) Correction: probing the dynamics of doxorubicin-DNA intercalation during the initial activation of apoptosis by fluorescence lifetime imaging microscopy (FLIM). PLoS One 7

  4. Motlagh NSH, Parvin P, Ghasemi F, Atyabi F (2016) Fluorescence properties of several chemotherapy drugs: doxorubicin, paclitaxel and bleomycin. Biomed Opt Express 7:2400–2406

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Duray PH, Cuono CB, Madri JA (1986) Demonstration of cutaneous doxorubicin extravasation by rhodamine-filtered fluorescence microscopy. J Surg Oncol 31:21–25

    CAS  PubMed  Google Scholar 

  6. Tasca E, Giudice AD, Galantini L, Schillén K, Giuliani AM, Giustini M (2019) A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles. J Colloid Interf Sci 540:593–601

    CAS  Google Scholar 

  7. Mohan P, Rapoport N (2010) Doxorubicin as a molecular nanotheranostic agent: effect of doxorubicin encapsulation in micelles or nanoemulsions on the ultrasound-mediated intracellular delivery and nuclear trafficking. Mol Pharm 7:1959–1973

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Shaikh AY, Shih JA (2012) Chemotherapy-induced cardiotoxicity. Curr Heart Fail Rep 9:117–127

    CAS  PubMed  Google Scholar 

  9. Chatterjee K, Zhang J, Honbo N, Karliner JS (2010) Doxorubicin cardiomyopathy. Cardiology. 115:155–162

    CAS  PubMed  Google Scholar 

  10. Lacko AG, Nair M, Paranjape S, Johnson S, McConathy WJ (2002) High density lipoprotein complexes as delivery vehicles for anticancer drugs. Anticancer Res 22:2045–2050

    CAS  PubMed  Google Scholar 

  11. Dai X, Yue Z, Eccleston ME, Swartling J, Slater NKH, Kaminsk CF (2008) Fluorescence intensity and lifetime imaging of free and micellar-encapsulated doxorubicin in living cells. Nanomedicine 4:49–56

    CAS  PubMed  Google Scholar 

  12. Trevisan MG, Poppi RJ (2003) Determination of doxorubicin in human plasma by excitation–emission matrix fluorescence and multi-way analysis. Anal Chim Acta 493:69–81

    CAS  Google Scholar 

  13. Prakash J, Mishra AK (2014) Quantification of doxorubicin in biofluids using white light excitation fluorescence, J. Biophotonics 7:607–616

    CAS  PubMed  Google Scholar 

  14. Ferreras FM, Wolfbeis OS, Gorris HH (2012) Dual lifetime referenced fluorometry for the determination of doxorubicin in urine. Anal Chim Acta 729:62–66

    Google Scholar 

  15. Shah S, Chandra A, Kaur A, Sabnis N, Lacko A, Gryczynski Z, Fudala R, Gryczynski I (2017) Fluorescence properties of doxorubicin in PBS buffer and PVA films. J Photochem Photobiol B 170:65–69

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Sharma RK, Shaikh S, Ray D, Aswal VK (2018) Binary mixed micellar systems of PEO-PPO-PEO block copolymers for lamotrigine solubilization: a comparative study with hydrophobic and hydrophilic copolymer, J Polym Res , 25

  17. Wei Z, Hao J, Yuan S, Li Y, Juan W, Sha X, Fang X (2009) Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. Int J Pharm 376:176–185

    CAS  PubMed  Google Scholar 

  18. Das RK, Kasoju N, Bora U (2009) Encapsulation of curcumin in alginate-chitosan-Pluronic composite nanoparticles for delivery to cancer cells. Nanomed: Nanotechnol Biol Med 6:153–160

    Google Scholar 

  19. Han LM, Guo J, Zhang LJ, Wang QS, Fang XL (2006) Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123. Acta Pharmacol Sin 27:747–753

    CAS  PubMed  Google Scholar 

  20. Liu Z, Liu D, Wang L, Zhang J, Zhang N (2011) Docetaxel-loaded Pluronic P123 polymeric micelles: in vitro and in vivo evaluation. Int J Mol Sci 11:1684–1696

    Google Scholar 

  21. Mohanty ME, Rao VJ, Mishra AK (2014) A fluorescence study on the interaction of telmisartan in triblock polymers Pluronic P123 and F127, Spectrochim. Acta A 121:330–338

    CAS  Google Scholar 

  22. Wanka G, Hoffmann H, Ulbricht W (1994) Phase diagrams and aggregation behavior of poly (oxyethylene)-poly (oxypropylene) -poly( oxyethylene) Triblock copolymers in aqueous solutions. Macromolecules 27:4145–4159

    CAS  Google Scholar 

  23. Alexandridis P, Holzwarth JF, Hatton TA (1994) Micellization of poly(ethy1ene oxide)-poly(propylene oxide)-poly(ethy1ene oxide) Triblock copolymers in aqueous solutions: thermodynamics of copolymer association. Macromolecules 27:2414–2425

    CAS  Google Scholar 

  24. Gao Q, Han X, Zhu J, Chen R, Sun B (2012) A polymer–drug conjugate for doxorubicin: synthesis and biological evaluation of Pluronic F127-doxorubicin amide conjugates. J Appl Polym Sci 124:4953–4960

    CAS  Google Scholar 

  25. Manaspon C, Pasuwat KV, Pimpha N (2012) Preparation of Folate-conjugated Pluronic F127/chitosan Core-Shell nanoparticles encapsulating doxorubicin for breast Cancer treatment, J Nanomaterials, 22

  26. Lai JR, Chang YW, Yen HC, Yuan NY, Liao MY, Hsu CY, Tsai JL, Lai PS (2010) Multifunctional doxorubicin/superparamagnetic iron oxide-encapsulated Pluronic F127 micelles used for chemotherapy/magnetic resonance imaging, J Appl Phys, 107

  27. Alakhov V, Klinski E, Li S, Pietrzynski G, Venne A, Batrakova E, Bronitch T, Kabanov AV (1999) Block copolymer-based formulation of doxorubicin. From cell screen to clinical trials. Colloids Surf. B: Biointerfaces 16:113–134

    CAS  Google Scholar 

  28. Choo ESG, Yu B, Xue J (2011) Synthesis of poly(acrylic acid) (PAA) modified Pluronic P123 copolymers for pH-stimulated release of doxorubicin. J Colloid Interface Sci 358:462–470

    CAS  PubMed  Google Scholar 

  29. Lee ES, Oh YT, Youn YS, Nam M, Park B, Yun J, Kim JH, Song HT, Oh KT (2011) Binary mixing of micelles using Pluronics for a nano-sized drug delivery system. Colloids Surf. B: Biointerfaces 82:190–195

    CAS  PubMed  Google Scholar 

  30. Htun T (2004) A negative deviation from stern–Volmer equation in fluorescence quenching. J Fluoresc 14:217–222

    CAS  PubMed  Google Scholar 

  31. Chen YY, Wu HC, Sun JS, Dong GC, Wang TW (2013) Injectable and Thermoresponsive self-assembled Nanocomposite hydrogel for long-term anticancer drug delivery. Langmuir 29:3721–3729

    CAS  PubMed  Google Scholar 

  32. R. Anand, F. Manoli, I. Manet, S. D. Mahammed, V. Agostoni, R. Grefb and S. Monti, β-Cyclodextrin polymer nanoparticles as carriers for doxorubicin and artemisinin: a spectroscopic and photophysical study, Photochem. Photobiol. Sci., 2012, 11, 1285–1292

  33. Ghosh S, Mandal U, Adhikari A, Bhattacharyya K (2009) Study of diffusion of organic dyes in a Triblock copolymer micelle and gel by fluorescence correlation spectroscopy. Chem Asian J 4:948–954

    CAS  PubMed  Google Scholar 

  34. George S, Kumbhakar M, Singh PK, Ganguly R, Nath S, Pal H (2009) Fluorescence spectroscopic investigation to identify the micelle to gel transition of aqueous Triblock copolymer solutions. J Phys Chem B 113:5117–5127

    CAS  PubMed  Google Scholar 

  35. Angeloni L, Smulevich G, Marzocchi MP (1982) Absorption, fluorescence and resonance Raman spectra of Adriamycin and its complex with DNA Spectrochim. Acta Part A 38:213–217

    Google Scholar 

  36. Smulevich G, Angeloni L, Giovannardi S, Marzocchi MP (1982) Resonance Raman and polarized light infrared spectra of 1,4-Dihydroxyanthraquinone, vibrational studies of the ground and excited electronic states. Chem Phys 65:313–322

    CAS  Google Scholar 

  37. Swain J, Mishra AK (2016) Nile red fluorescence for quantitative monitoring of micropolarity and microviscosity of pluronic F127 in aqueous media. Photochem Photobiol Sci 15:1400–1407

    CAS  PubMed  Google Scholar 

  38. Airoldi M, Barone G, Gennaro G, Giuliani AM, Giustini M (2014) Interaction of doxorubicin with polynucleotides. A Spectroscopic Study. Biochemistry 53:2197–2207

    CAS  PubMed  Google Scholar 

  39. Mohapatra M, Mishra AK (2011) Photophysical behaviour of fisetin in dimyristoylphosphatidylcholine liposome membrane. J Phys Chem B 115:9962–9970

    CAS  PubMed  Google Scholar 

  40. Mohapatra M, Subuddhi U, Mishra AK (2009) Photophysical behavior of ground state anion and phototautomer of 3-hydroxyflavone in liposome membrane. Photochem. Photobiol. Sc. 8:1373–1378

    CAS  Google Scholar 

  41. Qu P, Lu H, Yan S, Zhou D, Lu Z (2009) Investigations of effects of environmental factors in unfolding/refolding pathway of proteins on 8-anilino-1-naphthalene-sulfonic acid (ANS) fluorescence. J Mol Struct 936:187–193

    CAS  Google Scholar 

  42. Lakowicz JR (2006) Principles of fluorescence spectroscopy, Kluwer Academic, Plenum Publishers, New York

  43. Cezanne LD, Sautereau AM, Tocanne JF (1989) Localization of adriamycin in model and natural membranes influence of lipid molecular packing. Eur I Biochem 81:695–702

    Google Scholar 

  44. Gallois L, Fiallo M, Laigle A, Priebe W, Suillerot AG (1996) The overall partitioning of anthracyclines into phosphatidyl-containing model membranes depends neither on the drug charge nor the presence of anionic phospholipids. Eur J Biochem 241:879–887

    CAS  PubMed  Google Scholar 

  45. Pragatheeswaran AM, Chen SB (2013) Effect of chain length of PEO on the gelation and micellization of the Pluronic F127 copolymer aqueous system. Langmuir 29:9694–9701

    CAS  PubMed  Google Scholar 

  46. Dutra LMU, Ribeiro MENP, Cavalcante IM, Brito DHA, Semião LM, Silva RF, Fechine PBA, Yeates SG, Ricardo NMPS (2015) Binary mixture micellar systems of F127 and P123 for griseofulvin solubilisation. Polímeros 25:433–439

    Google Scholar 

  47. Oh KT, Bronich TK, Kabanov AV (2004) Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers, J. Control Release 94:411–422

    CAS  Google Scholar 

  48. Lee ES, Oh YT, Youn YS, Nam M, Park B, Yun J, Kim JH, Song HT, Oh KT (2011) Binary mixing of micelles using Pluronics for a nano-sized drug delivery system. Colloids Surf. B 82:190–195

    CAS  Google Scholar 

  49. Suna P, Misra PK (2018) Effect of ionic and nonionic surfactants on the phase behaviour and physicochemical characteristics of pseudoternary systems involving polyoxyethylene (20) sorbitan monooleate. Surfaces and Interfaces 10:19–26

    CAS  Google Scholar 

  50. Pellosi DS, Moret F, Fraix A, Marino N, Maiolino S, Gaio E, Hioka N, Reddi E, Sortino S, Quaglia F (2016) Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells. Int J Nanomedicine 11:4479

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Xue Q, Ren H, Xu C, Wang G, Ren C, Hao J, Ding D (2015) Nanospheres of doxorubicin as cross-linkers for a supramolecular hydrogelation. Sci Rep 5:8764

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank Prof Vaidya Jayathirtha Rao (IICT Hyderabad, India) and Prof Ashok Kumar Mishra (IIT Madras, India) for their valuable discussion and help in collecting fluorescence lifetime data. Dr. M. Mohapatra and Mr. S. K. Behera acknowledge the DST- Science and Engineering Research Board (SERB) (Grant number: ECR/2016/000692), Government of India, and TEQIP- III, VSSUT Burla for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Monalisa Mohapatra.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Behera, S.K., Mohanty, M.E. & Mohapatra, M. A Fluorescence Study of the Interaction of Anticancer Drug Molecule Doxorubicin Hydrochloride in Pluronic P123 and F127 Micelles. J Fluoresc 31, 17–27 (2021). https://doi.org/10.1007/s10895-020-02630-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-020-02630-y

Keywords

Navigation