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.
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References
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
Karukstis KK, Thompson EHZ, Whiles JA, Rosenfeld RJ (1998) Deciphering the fluorescence signature of daunomycin and doxorubicin. Biophys Chem 73:249–263
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
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
Duray PH, Cuono CB, Madri JA (1986) Demonstration of cutaneous doxorubicin extravasation by rhodamine-filtered fluorescence microscopy. J Surg Oncol 31:21–25
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
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
Shaikh AY, Shih JA (2012) Chemotherapy-induced cardiotoxicity. Curr Heart Fail Rep 9:117–127
Chatterjee K, Zhang J, Honbo N, Karliner JS (2010) Doxorubicin cardiomyopathy. Cardiology. 115:155–162
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
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
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
Prakash J, Mishra AK (2014) Quantification of doxorubicin in biofluids using white light excitation fluorescence, J. Biophotonics 7:607–616
Ferreras FM, Wolfbeis OS, Gorris HH (2012) Dual lifetime referenced fluorometry for the determination of doxorubicin in urine. Anal Chim Acta 729:62–66
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Htun T (2004) A negative deviation from stern–Volmer equation in fluorescence quenching. J Fluoresc 14:217–222
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
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
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
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
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
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
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
Airoldi M, Barone G, Gennaro G, Giuliani AM, Giustini M (2014) Interaction of doxorubicin with polynucleotides. A Spectroscopic Study. Biochemistry 53:2197–2207
Mohapatra M, Mishra AK (2011) Photophysical behaviour of fisetin in dimyristoylphosphatidylcholine liposome membrane. J Phys Chem B 115:9962–9970
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
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
Lakowicz JR (2006) Principles of fluorescence spectroscopy, Kluwer Academic, Plenum Publishers, New York
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
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
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
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
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
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
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
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
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
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.
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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
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DOI: https://doi.org/10.1007/s10895-020-02630-y