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Thermoresponsive phase behavior and nanoscale self-assembly generation in normal and reverse Pluronics®

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Abstract

Self-assembly generation in block copolymers (BCPs): normal Pluronics® (L31, L64, L35, P65) and reverse Pluronics® (31R1, 17R4, 25R4, 10R5) are scrutinized in single/ mixed aqueous environment systems. Solutions up to 10%w/v in investigated systems remained transparent up to ambient temperature while on progressive heating they attained their cloud point (CP). The critical micelle temperature (CMT) was evaluated by fluorescence spectroscopy, which is further complemented by dynamic light scattering (DLS) and small-angle light scattering (SANS). L31 showed phase separation (2ϕ) at ~ 30 °C without any micelle formation. L64, L35, and P65 formed micelles at high temperatures with some growth close to CP while all reverse Pluronics® formed no micelles until CP. The micellar parameters were reinforced from scattering as a function of temperature. Furthermore, these nanoscale micellar aggregates were explored qualitatively and quantitatively as potential nanocargos for anticancer (curcumin) drug to understand the cytotoxic effect using MTT assay.

Graphical Abstract

Plausible micellar transition and phase behavior in block copolymers (BCPs) with contrast block structure as a function of temperature.

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References

  1. Kuperkar K, Tiwari S, Bahadur P (2020) Self-assembled block copolymer nanoaggregates for drug delivery applications. Applications of polymers in drug delivery, Second Edition Elsevier, 15, 423–447, eBook ISBN: 978–0–12–819659–5

  2. Li X, Park E, Hyun K (2018) Rheological analysis of core-stabilized Pluronic F127 by semi-interpenetrating network (SIPN) in aqueous solution. J Rheol 62:107–120

    Article  CAS  Google Scholar 

  3. Rahdar A, Kazemi S, Askari F (2018) Pluronic as nano-carier platform for drug delivery systems. Nanomed Res J 3:174–179

    Google Scholar 

  4. Zarrintaj P, Ahmadi Z, Saeb M, Mozafari M (2018) Poloxamer-based stimuli-responsive biomaterials Mater Today: Proceedings 5:15516–15523

    CAS  Google Scholar 

  5. Kabanova A, Batrakova E, Alakhov V (2002) Pluronic® block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release 82:189–212

    Article  Google Scholar 

  6. Patel D, Patel D, Ray D, Kuperkar K, Aswal V, Bahadur P (2021) Single and mixed Pluronics micelles with solubilized hydrophobic additives: underscoring the aqueous solution demeanor and micellar transition. J Mol Liq 343:117625–117635

    Article  CAS  Google Scholar 

  7. Pitto-Barry A, Barry N (2014) Pluronic® block-copolymers in medicine: from chemical and biological versatility to rationalization and clinical advances. Polym Chem 5:3291–3297

    Article  CAS  Google Scholar 

  8. D’Errico G, Paduano L, Ortona O, Mangiapia G, Coppola L, Celso F (2011) Temperature and concentration effects on supramolecular aggregation and phase behavior for poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(propylene oxide) copolymers of different concentration in aqueous mixtures. J Coll Interf Sci 359:179–188

    Article  Google Scholar 

  9. Akash M, Rehman K, Chen S (2014) Pluronic F127-based thermosensitive gels for delivery of therapeutic proteins and peptides. Polym Rev 54:573–597

    Article  CAS  Google Scholar 

  10. Escobar-Chávez J, López-Cervantes M, Naïk A, Kalia Y, Quintanar-Guerrero D, Ganem-Quintanar A (2006) Applications of thermoreversible Pluronic F-127 gels in pharmaceutical formulations. J Pharm Pharm Sci 9:339–358

    Google Scholar 

  11. Jalaal M (2017) On the rheology of Pluronic F127 aqueous solutions. J Rheol 61:139–146

    Article  CAS  Google Scholar 

  12. Guragain S, Bastakoti B, Malgras V, Nakashima K, Yamauchi Y (2015) Multi-stimuli-responsive polymeric materials. Chem Eur J 21:13164–13174

    Article  CAS  Google Scholar 

  13. Lin Y, Paschalis A (2000) Small-angle neutron scattering investigation of the temperature-dependent aggregation behavior of the block copolymer Pluronic L64 in aqueous solution. Langmuir 16:8555–8561

    Article  Google Scholar 

  14. Hung-Wei T, Ya-Huei H, Jing-Han W, Li-Jen C (2008) Novel behavior of heat of micellization of Pluronics F68 and F88 in aqueous solutions. Langmuir 24:13858–13862

    Article  Google Scholar 

  15. Gangul R, Aswal V, Hassan P, Gopalakrishnan I, Kulshreshtha S (2006) Effect of SDS on the self-assembly behavior of the PEO-PPO-PEO triblock copolymer (EO)20(PO)70(EO)20. J Phys Chem B 110:9843–9849

    Article  Google Scholar 

  16. Patel D, Jana R, Lin M, Kuperkar K, Seth D, Chen L, Bahadur P, (2021) Revisiting the salt-triggered self-assembly in very hydrophilic triblock copolymer Pluronic® F88 using multitechnique approach. Coll Polym Sci 229–243

  17. Alvarez-Ramirez J, Fernández V, Macías E, Rharbi Y, Taboada P, Gámez-Corrales R, Puiga J, Soltero J (2009) Phase behavior of the Pluronic P103/water system in the dilute and semi-dilute regimes. J Coll Interf Sci 333:655–662

    Article  CAS  Google Scholar 

  18. Basak R, Bandyopadhyay R (2013) Encapsulation of hydrophobic drugs in Pluronic F127 micelles: effects of drug hydrophobicity, solution temperature, and pH. Langmuir 29:4350–4356

    Article  CAS  Google Scholar 

  19. Popovici C, Popa M, Sunel V, Atanase L, Ichim D (2022) Drug delivery systems based on Pluronic micelles with antimicrobial activity. Polymer 14:3007–3022

    Article  CAS  Google Scholar 

  20. Mata J, Majhi P, Guo C, Liu H, Bahadur P (2005) Concentration, temperature, and salt-induced micellization of a triblock copolymer Pluronic L64 in aqueous media. J Coll Interf Sci 292:548–556

    Article  CAS  Google Scholar 

  21. Henda M, Gharbi A (2017) Temperature, concentration and salt effect on F68 tri-block copolymer in aqueous solution: Rheological Study. Polym Sci 59:445–450

    Google Scholar 

  22. Anderson B, Cox S, Ambardekar A, Mallapragada S (2002) The effect of salts on the micellization temperature of aqueous poly(ethylene oxide)-b-poly(propylene oxide)- b-poly(ethylene oxide) solutions and the dissolution rate and water diffusion coefficient in their corresponding gels. J Pharm Sci 91:180–188

    Article  CAS  Google Scholar 

  23. Patel V, Ray D, Bahadur A, Ma J, Aswal V, Bahadur P (2018) Pluronic®-bile salt mixed micelles. Coll Surf B 166:119–126

    Article  CAS  Google Scholar 

  24. Pérez-Sánchez G, Vicente F, Schaeffer N, Cardoso I, Ventura S, Jorge M, Coutinho J (2019) Rationalizing the phase behavior of triblock copolymers through experiments and molecular simulations. J Phys Chem C 123:21224–21236

    Article  Google Scholar 

  25. Kumi B, Hammouda B, Greer S (2014) Self-assembly of the triblock copolymer 17R4 poly(propylene oxide)14 -poly(ethylene oxide)24-poly(propylene oxide)14 in D2O. J Coll Interf Sci 434:201–207

    Article  CAS  Google Scholar 

  26. Chowdhry B, Snowdena M, Leharne S (1999) Scanning calorimetric investigations of phase transitions in a PPO-PEO-PPO block copolymer. Eur Polym J 35:273–278

    Article  CAS  Google Scholar 

  27. Guiraud S, Alimi-Guez D, Wittenberghe L, Scherman D, Kichler A (2011) The reverse block copolymer Pluronic 25R2 promotes DNA transfection of skeletal muscle. Macromol Biosci 11:590–594

    Article  CAS  Google Scholar 

  28. Dutra L, Ribeiro M, Cavalcante I, Brito D, Semião L, Silva R, Fechine P, Yeates S, Ricardo N (2015) Binary mixture micellar systems of F127and P123 for griseofulvin solubilization. Polímeros 25:433–439

    Article  CAS  Google Scholar 

  29. El-Dahmy R, Elsayed I, Elshafeey A, Gawad N, El-Gazayerly O (2014) Optimization of long circulating mixed polymeric micelles containing vinpocetine using simple lattice mixture design, in-vitro and in vivo characterization. International J Pharmaceutics 477:39–46

    Article  CAS  Google Scholar 

  30. Zhao L, Du J, Duan Y, Zang Y, Zhang H, Yang C, Cao F, Zhai G (2012) Curcumin loaded mixed micelles composed of Pluronic P123 and F68: preparation, optimization and in-vitro characterization. Coll Surf B 97:101–108

    Article  CAS  Google Scholar 

  31. Lage E, Pillai S, Pal H, Bahadur A, Casas M, Sández-Macho I, Bahadur P (2018) Urea induced changes in self-assembly and aggregate microstructures of amphiphilic star block copolymers with widely different hydrophobicity. Coll Surf A 537:259–267

    Article  CAS  Google Scholar 

  32. Patel D, Ray D, Kuperkar K, Pal H, Aswal V, Bahadur P (2020) Solubilization, micellar transition and biocidal assay of loaded antioxidants in Tetronic® 1304 Micelles. Polym Int 69:1097–1104

    Article  CAS  Google Scholar 

  33. Patel D, Ray D, Kuperkar K, Aswal V, Bahadur P (2020) Parabens induced spherical micelle to polymersome transition in thermo-responsive amphiphilic linear and star-shaped EO-PO block copolymers. J Mol Liq 316:113897–113908

    Article  CAS  Google Scholar 

  34. Patel D, Agarwal S, Ray D, Kuperkar K, Aswal V, Bahadur P (2021) An expedient in to the phase behaviour and scattering profile in PEO-PPO-PEO block copolymer mixed systems in aqueous solution. Coll Surf A 617:126330–126340

    Article  CAS  Google Scholar 

  35. Zhang W, Shi Y, Chen Y, Ye J, Sha X, Fang X (2011) Multifunctional Pluronic P123/F127 mixed polymeric micelles loaded with paclitaxel for the treatment of multidrug resistant tumors. Biomaterials 32:2894–2906

    Article  CAS  Google Scholar 

  36. Naskar B, Ghosh S, Moulik S (2012) Solution behavior of normal and reverse triblock copolymers (Pluronic L44 and 10R5) individually and in binary mixture. Langmuir 28:7134–7146

    Article  CAS  Google Scholar 

  37. Hassanzadeh S, Feng Z, Pettersson T, Hakkarainen M (2015) A proof-of-concept for folate-conjugated and quercetin-anchored Pluronic mixed micelles as molecularly modulated polymeric carriers for doxorubicin. Polymer 74:193–204

    Article  CAS  Google Scholar 

  38. Patel D, Rathod S, Tiwari S, Ray D, Kuperkar K, Aswal V, Bahadur P (2020) Self-Association in EO-BO-EO triblock copolymers as a nanocarrier template for sustainable release of anticancer drugs. J Phys Chem B 124:11750–11761

    Article  CAS  Google Scholar 

  39. Iurciuc-Tincu C, Cretan M, Purcar V, Popa M, Daraba O, Atanase L, Ochiuz L (2020) Drug delivery system based on pH-sensitive biocompatible poly(2-vinyl pyridine)-b-poly(ethylene oxide) nanomicelles loaded with curcumin and 5-fluorouracil. Polymers 12:1450–1469

    Article  CAS  Google Scholar 

  40. Song J, Liu Y, Guo Y, Zhong W, Guo Y, Guo L (2022) Nano–liposomes double loaded with curcumin and tetrandrine: preparation, characterization, hepatotoxicity and anti–tumor effects. Int J Mol Sci 23:6858–6871

    Article  CAS  Google Scholar 

  41. Iurciuc C, Atanase L, Jérôme C, Sol V, Martin P, Popa M, Ochiuz L (2021) Polysaccharides-based complex particles’ protective role on the stability and bioactivity of immobilized curcumin. Int J Mol Sci 22:3075–3099

    Article  CAS  Google Scholar 

  42. Wu J, Qi C, Wang H, Wang Q, SunJ DJ, Yu G, Gao Z, Zhang B, Tian G (2022) Curcumin and berberine coloaded liposomes for antihepatocellular carcinoma therapy by blocking the cross-talk between hepatic stellate cells and tumor cells. Front Pharmacol 13:961788

    Article  CAS  Google Scholar 

  43. Yadav V, Suresh S, Devi K, Yadav S (2009) Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. AAPS Pharm Sci Tech 10:752–762

    Article  CAS  Google Scholar 

  44. Patel D, Kuperkar K, Bahadur P (2022) Temperature stimulated self-association and micellar transition for star shaped normal and reverse EO-PO block copolymers and their mixed systems as potential use for anticancer drug solubilization. Soft Matter 18:4543–4553

    Article  CAS  Google Scholar 

  45. Kanoje B, Patel D, Kumar V, Sahoo S, Parikh J, Kuperkar K, (2019) Unraveling the solubilization and cytotoxicity study of poorly water-soluble anti-inflammatory drug in aqueous Gemini surfactants solution with physicochemical characterization and simulation study. Colloid Surf B, 179, 437–444

  46. Braunová A, Chytil P, Laga R, Šírová M, Machová D, Parnica J, Říhová B, Janoušková O, Etrych T (2020) Polymer nanomedicines based on micelle-forming amphiphilic or water soluble polymer-doxorubicin conjugates: comparative study of in-vitro and in-vivo properties related to the polymer carrier structure, composition, and hydrodynamic properties. J Controlled Release 321:718–733

    Article  Google Scholar 

  47. Shen T, Xu X, Guo L, Tang H, Diao T, Gan Z, Zhang G, Yu Q (2017) Efficient tumor accumulation, penetration and tumor growth inhibition achieved by polymer therapeutics: the effect of polymer architectures. Biomacromol 18:217–230

    Article  CAS  Google Scholar 

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Acknowledgements

Authors acknowledge Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Gujarat-INDIA for providing the instrumentation facility.

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Authors and Affiliations

  1. Department of Chemistry, Sardar Vallabhbhai National Institute of Technology (SVNIT), Ichchhanath, Surat, 395 007, Gujarat, India

    Dhruvi Patel & Ketan Kuperkar

  2. Biomedical Engineering, Indian Institute of Technology Gandhinagar (IITGn), Palaj, Gandhinagar, 382 355, Gujarat, India

    Payal Vaswani & Dhiraj Bhatia

  3. Radiation and Photochemistry Division, Bhabha Atomic Research Centre (BARC), Mumbai-400 085, Trombay, Maharashtra, India

    Sumana Sengupta & Sharmistha Dutta Choudhury

  4. Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400 094, India

    Sumana Sengupta & Sharmistha Dutta Choudhury

  5. Solid State Physics Division, Bhabha Atomic Research Centre (BARC), Trombay, Mumbai, 400 085, Maharashtra, India

    Debes Ray & Vinod K. Aswal

  6. Department of Chemistry, Veer Narmad South Gujarat University (VNSGU), Surat, 395007, Gujarat, India

    Pratap Bahadur

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  1. Dhruvi Patel
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  2. Payal Vaswani
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  3. Sumana Sengupta
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  7. Vinod K. Aswal
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  8. Ketan Kuperkar
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  9. Pratap Bahadur
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Contributions

Dhruvi Patel: experimental investigation, methodology, data fitting and analysis, writing and editing. Payal Vaswani and Dhiraj Bhatia: biological activity and analysis, writing—review and editing. Debes Ray, Sumana Sengupta, Sharmishtha Dutta Choudhury and Vinod K Aswal: formal analysis, data fitting, writing—review and editing. Ketan Kuperkar: conceptualization, methodology, writing—review and editing, supervision, project administration. Pratap Bahadur: conceptualization, writing—review and editing, supervision.

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Correspondence to Ketan Kuperkar.

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Patel, D., Vaswani, P., Sengupta, S. et al. Thermoresponsive phase behavior and nanoscale self-assembly generation in normal and reverse Pluronics®. Colloid Polym Sci 301, 75–92 (2023). https://doi.org/10.1007/s00396-022-05039-0

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  • DOI: https://doi.org/10.1007/s00396-022-05039-0

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