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Cyclo-matrix Poly(cyclotriphosphazene-co-kaempferol) Microspheres: Synthesis, Characterization, EPR Study and Their Controlled Drug Release Application

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Abstract

Cyclo-matrix polyphosphazene based microspheres offers a lot of promise for future applications owning to its uniform structures and unique characteristics. In this work, poly(cyclotriphosphazene-co-kaempferol) (CMPZ-KM) based microspheres were synthesized via precipitation polymerization. Several analytical techniques were applied to confirm the successful synthesis, surface morphology, average diameter size, crystallinity, thermal stability and the prepared microsphere’s particle size distribution. In order to analyze the cross-linking density and structural dynamics of the CMPZ-KM based microspheres, the electron paramagnetic resonance (EPR) spectroscopy was used. The observations reveal that the increased mole ratio of kaempferol has high influence on the density of the cross-linking of synthesized microspheres. In addition, the peak intensity and outer extreme separation (Azz) of (CMPZ-KM)-3/CPT based microspheres were decreased owing to incorporated of the drug molecules onto the surface of microspheres. Herein, the prepared microspheres were used as anticancer drug carriers, which exhibited 44.49 mg/g of drug loading efficiency system. The cumulative drug release of the (CMPZ-KM)-3/CPT microspheres were studied in two different pH media. The cumulative release was found to be 62.8 and 40.8% when the medium of pH kept 4.0 and 7.4, respectively at 37 °C after 518 h which are in controlled manner. Different kinetic models such 1st order and Zero order kinetic, Highuchi, Hixon Crowell’s and Korsmayer peppas were applied to the drug release data. The kinetic study showed that Highuchi, Hixon Crowell’s were best suited to the experimental data. The obtained result suggested that this approach can offers to design a new cyclo-matrix microspheres platform which helps their promising application in cancer therapy.

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References

  1. Dimitriou N, Pavlopoulou A, Tremi I, Kouloulias V, Tsigaridas G, Georgakilas A (2019) Prediction of gold nanoparticle and microwave-induced hyperthermia effects on tumor control via a simulation approach. Nanomaterials 9:167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mehmood S, Yu H, Wang L, Jian H, Uddin MA, Amin BU, Haq F, Fahad S, Haroon M (2023) Study on fully cross-linked poly(cyclotriphosphazene-co-epigallocatechin) nanospheres and their application as drug delivery carriers. Int J Polym Mater Polym Biomater. https://doi.org/10.1080/00914037.2023.2175825

    Article  Google Scholar 

  3. Mehmood S, Uddin MA, Yu H, Wang L, Amin BU, Haq F, Fahad S, Haroon M (2022) Study on synthesis of cross-linked poly(Cyclotriphosphazene-co-Luteolin) nanospheres and their Properties for Controlled Drug Delivery. Colloid Polym Sci 300:861–871

    Article  CAS  Google Scholar 

  4. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20

    Article  CAS  PubMed  Google Scholar 

  5. Su J, Chen F, Cryns VL, Messersmith PB (2011) Catechol polymers for pH-responsive, targeted drug delivery to cancer cells. J Am Chem Soc 133:11850–11853

    Article  CAS  PubMed Central  Google Scholar 

  6. Kumar S, Singh S, Senapati S, Singh AP, Ray B, Maiti P (2017) Controlled drug release through regulated biodegradation of poly(lactic acid) using inorganic salts. Int J Biol Macromol 104:487–497

    Article  CAS  PubMed  Google Scholar 

  7. Shim MS, Kwon YJ (2012) Stimuli-responsive polymers and nanomaterials for gene delivery and imaging applications. Adv Drug Deliv Rev 64:1046–1059

    Article  CAS  PubMed  Google Scholar 

  8. Cheng F, Peng X, Meng G, Pu Y, Luo K, He B (2020) Poly(ester-thioether) microspheres co-loaded with erlotinib and α-tocopheryl succinate for combinational therapy of non-small cell lung cancer. J Mater Chem B 8:1728–1738

    Article  CAS  PubMed  Google Scholar 

  9. Mehmood S, Uddin MA, Yu H, Wang L, Amin BU, Haq F, Fahad S, Haroon M (2022) Preparation of size-controlled poly(Cyclotriphosphazene-co-Resveratrol) Microspheres and their Properties as Drug Delivery Carriers. Iran Polym J 31:1225–1235

    Article  CAS  Google Scholar 

  10. Mehmood S, Yu H, Wang L, Hu J, Uddin MA, Amin BU, Haq F, Fahad S, Haroon M, Shen D, Xu J (2022) Studies on the synthesis and drug release behavior of cross-linked poly(Cyclotriphosphazene-co-Fluorescein) Microspheres. J Polym Environ 30:5119–5129

    Article  CAS  Google Scholar 

  11. Langer R (1990) New methods of drug delivery. Science 249:1527–1533

    Article  CAS  PubMed  Google Scholar 

  12. Alagusundaram M, Chetty C, Umashankari K, Badarinath AV, Lavanya C, Ramkanth DS (2009) Microspheres as a novel drug delivery sysytem-A review. Int J ChemTech Res 1:526–534

    CAS  Google Scholar 

  13. Varde NK, Pack DW (2004) Microspheres for controlled release drug delivery. Expert Opin Biol Ther 4:35–51

    Article  CAS  PubMed  Google Scholar 

  14. Wang W, Zhou S, Sun L, Huang C (2010) Controlled delivery of paracetamol and protein at different stages from core-shell biodegradable microspheres. Carbohydr Polym 79:437–444

    Article  CAS  Google Scholar 

  15. Umeki N, Sato T, Harada M, Takeda J, Saito S, Iwao Y, Itai S (2010) Preparation and evaluation of biodegradable microspheres containing a new potent osteogenic compound and new synthetic polymers for sustained release. Int J Pharm 392:42–50

    Article  CAS  PubMed  Google Scholar 

  16. Ang CY, Tan SY, Zhao Y (2014) Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy. Org Biomol Chem 12:4776–4806

    Article  CAS  PubMed  Google Scholar 

  17. Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6:688–701

    Article  CAS  PubMed  Google Scholar 

  18. Wang AZ, Langer R, Farokhzad OC (2012) Nanoparticle delivery of cancer drugs. Annu Rev Med 63:185–198

    Article  CAS  PubMed  Google Scholar 

  19. Colilla M, González B, Vallet-Regí M (2013) Mesoporous silica nanoparticles for the design of smart delivery nanodevices. Biomaterials Science 1:114–134

    Article  CAS  PubMed  Google Scholar 

  20. Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–16

    Article  CAS  PubMed  Google Scholar 

  21. Zhang H, Ma X, Nguyen KT, Zhao Y (2013) Biocompatible pillararene-assembly-based carriers for dual bioimaging. ACS Nano 7:7853–7863

    Article  CAS  PubMed  Google Scholar 

  22. Wang X, Yucel T, Lu Q, Hu X, Kaplan DL (2010) Silk nanospheres and microspheres from silk/pva blend films for drug delivery. Biomaterials 31:1025–1035

    Article  CAS  PubMed  Google Scholar 

  23. Hou S, Chen S, Dong Y, Gao S, Zhu B, Lu Q (2018) Biodegradable cyclomatrix polyphosphazene nanoparticles: a novel pH-responsive drug self-framed delivery system. ACS Appl Mater & Interfaces 10:25983–25993

    Article  CAS  Google Scholar 

  24. Mehmood S, Wang L, Yu H, Haq F, Fahad S, A. Bilal ul, M. Alim Uddin, M. Haroon, (2020) Recent progress on the preparation of cyclomatrix-polyphosphazene based micro/nanospheres and their application for drug release. ChemistrySelect 5:5939–5958

    Article  CAS  Google Scholar 

  25. Wang L, Yang YX, Shi X, Mignani S, Caminade AM, Majoral JP (2018) Cyclotriphosphazene core-based dendrimers for biomedical applications: an update on recent advances. J Mater Chem B 6:884–895

    Article  PubMed  Google Scholar 

  26. Chang F, Huang X, Wei H, Chen K, Shan C, Tang X (2014) Intrinsically fluorescent hollow spheres based on organic–inorganic hybrid polyphosphazene material: synthesis and application in drug release. Mater Lett 125:128–131

    Article  CAS  Google Scholar 

  27. Metinoğlu Örüm S, Süzen Demircioğlu Y (2019) One-pot synthesis and characterization of crosslinked polyphosphazene dopamine microspheres for controlled drug delivery applications. J Macromol Sci, Part A 56:854–859

    Article  Google Scholar 

  28. Mehmood S, Yu H, Wang L, H, Jian, M. Alim Uddin, A. Bilal ul, F. Haq, S. Fahad, M. Haroon, (2022) Cross-linked poly(cyclotriphosphazene-co-phloretin) Microspheres and their application for controlled drug delivery. Macromol Res. https://doi.org/10.1007/s13233-022-0066-0

    Article  Google Scholar 

  29. Ozay H, Ozay O (2014) Synthesis and characterization of drug microspheres containing phosphazene for biomedical applications. Colloids Surf, A 450:99–105

    Article  CAS  Google Scholar 

  30. Mehmood S, Yu H, Wang L, Jian H, Alim Uddin M, Bilal ul A, Haq F, Fahad S, Haroon M (2022) Preparation of size-controlled poly(cyclotriphosphazene-co-resveratrol) microspheres and their properties as drug delivery carriers. Iranian Polymer Journal DOI. https://doi.org/10.1007/s13726-022-01070-8

    Article  Google Scholar 

  31. Mehmood S, Yu H, Wang L, Jian H, Alim Uddin M, Bilal ul A, Haq F, Fahad S, Haroon M (2022) One-pot synthesis of size-controlled poly(cyclotriphosphazene-co-hesperetin) microspheres and their properties as drug delivery carriers. ChemistrySelect. https://doi.org/10.1002/slct.202200273

    Article  Google Scholar 

  32. Hou SL, Chen SS, Huang ZJ, Lu QH (2019) Dual-responsive polyphosphazene as a common platform for highly efficient drug self-delivery. J Mater Chem B 7:4319–4327

    Article  CAS  Google Scholar 

  33. Jing X, Zhi Z, Jin L, Wang F, Wu Y, Wang D, Yan K, Shao Y, Meng L (2019) pH/redox dual-stimuli-responsive cross-linked polyphosphazene nanoparticles for multimodal imaging-guided chemo-photodynamic therapy. Nanoscale 11:9457–9467

    Article  CAS  PubMed  Google Scholar 

  34. Lu Q, Meng L, Xu C, Zhou X, Li H, Long J (2015) One-pot synthesis of highly cross-linked fluorescent polyphosphazene nanoparticles for cell imaging, Polym Chem. 6

  35. Wang D, Hu Y, Meng L, Wang X, Lu Q (2015) One-pot synthesis of fluorescent and cross-linked polyphosphazene nanoparticles for highly sensitive and selective detection of dopamine in body fluids. RSC Adv 5:92762–92768

    Article  CAS  Google Scholar 

  36. Sun L, Liu T, Li H, Yang L, Meng L, Lu Q, Long J (2015) Fluorescent and cross-linked organic-inorganic hybrid nanoshells for monitoring drug delivery. ACS Appl Mater Interfaces 7:4990–4997

    Article  CAS  PubMed  Google Scholar 

  37. Metinoğlu Örüm S, Demircioğlu Y (2018) Cross-linked polyphosphazene nanospheres with anticancer quercetin: synthesis, spectroscopic, thermal properties, and controlled drug release. Macromol Res 26:671–679

    Article  Google Scholar 

  38. Mehmood S, Yu H, Wang L, Jian H, Alim Uddin M, Bilal ul A, Haq F, Fahad S, Haroon M (2022) Study on synthesis of cross-linked poly(cyclotriphosphazene-co-luteolin) nanospheres and their properties for controlled drug delivery. Colloid Polym Sci. https://doi.org/10.1007/s00396-22-04992-0

    Article  Google Scholar 

  39. Wang Z, Hu M, Hu S, Han J, Wang Z, Chen Y, Huang C, Fu L, Zhang Z (2018) Facile one-pot synthesis of multifunctional polyphosphazene nanoparticles as multifunctional platform for tumor imaging. Anal Bioanal Chem 410:3723–3730

    Article  CAS  PubMed  Google Scholar 

  40. Wei W, Huang X, Zhao X, Zhang P, Tang X (2010) A rapid and efficient strategy for preparation of super-hydrophobic surface with cross-linked cyclotriphosphazene/6F-bisphenol A copolymer microspheres. Chem Commun 46:487–489

    Article  CAS  Google Scholar 

  41. Zhu Y, Huang X, Li W, Fu J, Tang X (2008) Preparation of novel hybrid inorganic–organic microspheres with active hydroxyl groups using ultrasonic irradiation via one-step precipitation polymerization. Mater Lett 62:1389–1392

    Article  CAS  Google Scholar 

  42. Junk MJN, Jonas U, Hinderberger D (2008) EPR spectroscopy reveals nanoinhomogeneities in the structure and reactivity of thermoresponsive hydrogels. Small 4:1485–1493

    Article  CAS  PubMed  Google Scholar 

  43. Constantin MM, Corbu CG, Tanase C, Codrici E, Mihai S, Popescu ID, Enciu AM, Mocanu S, Matei I, Ionita G (2019) Spin probe method of electron paramagnetic resonance spectroscopy-A qualitative test for measuring the evolution of dry eye syndrome under treatment. Anal. Methods 11:965–972

    Article  CAS  Google Scholar 

  44. Karuppuswamy P, Reddy Venugopal J, Navaneethan B, Luwang Laiva A, Ramakrishna S (2015) Polycaprolactone nanofibers for the controlled release of tetracycline hydrochloride. Mater Lett 141:180–186

    Article  CAS  Google Scholar 

  45. Colombo M, de Lima Melchiades G, Michels LR, Figueiró F, Bassani VL, Teixeira HF, Koester LS (2019) Solid dispersion of kaempferol: formulation development, characterization, and oral bioavailability assessment. AAPS PharmSciTech 20:106

    Article  CAS  PubMed  Google Scholar 

  46. Sathyadevi M, Subramanian S (2015) Extraction, isolation and characterization of bioactive flavonoids from the fruits of physalis peruviana linn extract. Asian J Pharm Clin Res 8:152–157

    CAS  Google Scholar 

  47. Süzen Y, Metinoğlu Örüm S (2017) Novel cyclomatrix-type polyphosphazene microspheres crosslinked with octachlorocyclotetraphosphazene: preparation and characterization. Anadolu Univ J Sci Technol-A Appl Sci Eng 18:973–987

    Google Scholar 

  48. Wei X, Zhang G, Zhou L, Li J (2017) Synthesis and characterization of hydrophobic amino-based polyphosphazene microspheres with different morphologies via two strategies. Appl Surf Sci 419:744–752

    Article  CAS  Google Scholar 

  49. Fu J, Wang M, Zhang C, Xu Q, Huang X, Tang X (2012) Controlled fabrication of noble metal nanoparticles loaded on the surfaces of cyclotriphosphazene-containing polymer nanotubes. J Mater Sci 47:1985–1991

    Article  CAS  Google Scholar 

  50. Li Z, Wang G, Ren W, Zhang A, An L, Tian Y (2016) Cyclotriphosphazene-containing polymeric nanotubes: synthesis, properties, and formation mechanism. J Mater Sci 51:4096–4103

    Article  CAS  Google Scholar 

  51. Hubina AV, Pogodaev AA, Sharoyko VV, Vlakh EG, Tennikova TB (2016) Self-assembled spin-labeled nanoparticles based on poly(amino acids). React Funct Polym 100:173–180

    Article  CAS  Google Scholar 

  52. Campestrini S, Corvaja C, Nardi MD, Ducati C, Franco L, Maggini M, Meneghetti M, Menna E, Ruaro G (2008) Investigation of the inner environment of carbon nanotubes with a fullerene-nitroxide probe. Small 4:350–356

    Article  CAS  PubMed  Google Scholar 

  53. Beghein N, Rouxhet L, Dinguizli M, Brewster ME, Ariën A, Préat V, Habib JL, Gallez B (2007) Characterization of self-assembling copolymers in aqueous solutions using electron paramagnetic resonance and fluorescence spectroscopy. J Control Release 117:196–203

    Article  CAS  PubMed  Google Scholar 

  54. Lock LL, LaComb M, Schwarz K, Cheetham AG, Lin Y-A, Zhang P, Cui H (2013) Self-assembly of natural and synthetic drug amphiphiles into discrete supramolecular nanostructures. Faraday Discuss 166:285–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, Hazara University, Mansehra, 21300, KPK, Pakistan

    Sahid Mehmood & Farman Ali

  2. Institute of Chemical Sciences, Gomal University, D.I.Khan, 29050, Pakistan

    Fazal Haq

  3. Faculty of Agriculture, Gomal University, D.I.Khan, 29050, Pakistan

    Mehwish Kiran

  4. School of Engineering, Westlake University, Hangzhou, 310024, China

    Tariq Aziz

  5. Gomal Center of Biochemistry and Biotechnology, Gomal University, D.I.Khan, 29050, Pakistan

    Arshad Farid

  6. Department of Chemistry, University of Turbat, Balochistan, 92600, Pakistan

    Muhammad Haroon

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Contributions

SM: has done the reaction. FH and MK: revised the topic several times and provided their suggestions and gave the final approval of the last version to be submitted. FU: and TA: revised the final version and provided his comments focusing on the synthetic routes. MH: helped to design the reaction parameters and conditions by providing in depth analysis. AF: participated in jotting down the application section.

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Correspondence to Fazal Haq.

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Mehmood, S., Haq, F., Kiran, M. et al. Cyclo-matrix Poly(cyclotriphosphazene-co-kaempferol) Microspheres: Synthesis, Characterization, EPR Study and Their Controlled Drug Release Application. J Polym Environ 31, 4817–4828 (2023). https://doi.org/10.1007/s10924-023-02890-2

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