Lantanit Metallerle İşaretlenmiş Kolin Klorür Enkapsüle PLGA Nanopartikülleri

Öz

Burada, kolin klorür kontrollü salınımını sağlamak için PLGA nanoparçacıklarına yüklenmiştir. Bunların kapsülleme verimleri (EE) ve yükleme kapasiteleri (LC) belirlenmiştir. Ayrıca üretilen nanopartiküller Zetasizer, FT-IR, SEM ve XRD ile karakterize edilmiştir. Nanopartiküllerin yüzeyleri, üç farklı görüntüleme tekniği ile tanı ve tedavi kapasitesini genişletmek için üç farklı doğal lantanit metali Europium, Gadolinium ve Lutetium ile işaretlenerek işlevselleştirilmiştir. Nanopartiküllerin metal işaretlemesi SEM-EDX analizi ile doğrulanmıştır. Kolin klorür yüklü nanoparçacıkların EE’si %62.5-%88.9 arasında değişmiştir. Kolin klorür yüklü nanoparçacıkların LC’si %34.9 ile %61.4 arasında değişmiştir. Serbest nanopartiküllerin Zetasizer analizinden elde edilen ortalama boyut dağılımı 261.0 ± 7.598 nm idi. Kapsüllenmiş nanoparçacıkların Z-ortalama boyutu da 257.5 ila 270 nm arasındaydı. Oldukça negatif zeta potansiyeli, örneğin, serbest NP’ler için -17.85 ± 0.165 mV, nanoparçacıkların yeterince kararlı olduğunu göstermiştir. Metal işaretli NP’lerin element haritalaması, işaretleme prosedürünü doğrulamıştır. Terapötik kolin klorürür yüklü farklı metal işaretli nanoparçacıkların elde edilmesi ile aslında ortak hedefe yönelik ve farklı görüntüleme ve dedeksiyon teknikleri ile limitasyonları ortadan kaldırma beceresine sahip teranostik ajanlar üretilmiştir.

Anahtar Kelimeler

• Kolin klorür
• PLGA
• Lantanitler

Choline Chloride Encapsulated PLGA Nanoparticles Labelled with Lanthanide Metals

Abstract

Herein, choline chloride was loaded into PLGA nanoparticles to ensure its controlled release. Encapsulation efficiencies (EE) and loading capacities (LC) of them were determined. Also, the produced nanoparticles were analyzed with Zetasizer, FT-IR, SEM, and XRD. The surfaces of the nanoparticles were functionalized by labeling with three different natural lanthanide metals Europium, Gadolinium, and Lutetium to expand diagnostic and therapeutic capabilities with three different imaging tecniques. Metal labeling of the nanoparticles was confirmed with SEM-EDX analysis. EE of the choline chloride nanoparticles were ranging between 62.5%-88.9%. LC of the choline chloride nanoparticles varied from 34.9 to 61.4. The mean size distribution obtained from the Zetasizer analysis of the free nanoparticles was 261.0 ± 7.598 nm. The Z-average size of the encapsulated nanoparticles also varied from 257.5 to 270 nm. The quite negative zeta potential, for example, -17.85 ± 0.165 mV for free NPs showed that the nanoparticles were sufficiently stable. The elemental mapping of the metal labeled NPs verified the labeling procedure. By obtaining therapeutic choline chloride-loaded nanoparticles with different metal labels, theranostic agents with common target and the ability to eliminate limitations with different imaging and detection techniques have been produced.

Keywords

• Choline chloride
• PLGA
• Lanthanides

Kaynakça

1. Abamor, E. S., Allahverdiyev, A., Tosyali, O. A., Bagirova, M., Acar, T., Mustafaeva, Z., & Derman, S. (2019). Evaluation of in vitro and in vivo immunostimulatory activities of poly (lactic-co-glycolic acid) nanoparticles loaded with soluble and autoclaved Leishmania infantum antigens: A novel vaccine candidate against visceral leishmaniasis. Asian Pacific Journal of Tropical Medicine, 12(8), 353-364.
2. Acar, T., & Ucar, B. (2022). Angiotensin (1-7)-Stearic Acid Conjugate: Synthesis and Characterization. Journal of the Turkish Chemical Society Section A: Chemistry, 9(2), 331-338.
3. Al‐Saeedi, F. J., & Cheng, B. (2013). Choline treatment affects the liver reticuloendothelial system and plasma fatty acid composition in diabetic rats. Clinical Physiology and Functional Imaging, 33(4), 293-301.
4. Arias, N., Arboleya, S., Allison, J., Kaliszewska, A., Higarza, S. G., Gueimonde, M., & Arias, J. L. (2020). The relationship between choline bioavailability from diet, intestinal microbiota composition, and its modulation of human diseases. Nutrients, 12(8), 2340. Brauner, B., Semmler, J., Rauch, D., Nokaj, M., Haiss, P., Schwarz, P., . . . Gabor, F. (2020). Trimethoprim-loaded PLGA nanoparticles grafted with WGA as potential intravesical therapy of urinary tract infections—Studies on adhesion to SV-HUCs under varying time, pH, and drug-loading conditions. ACS omega, 5(28), 17377-17384.
5. Cebeci, C., Ucar, B., Acar, T., & Erden, I. (2021). Colorimetric detection of hydrogen peroxide with gadolinium complex of phenylboronic acid functionalized 4, 5-diazafluorene. Inorganica chimica acta, 522, 120386.
6. Cicalese, L. (2022). Hepatocellular Carcinoma (HCC). Retrieved from https://emedicine.medscape.com/article/197319-overview
7. Dangi, R., & Shakya, S. (2013). Preparation, optimization and characterization of PLGA nanoparticle. International Journal of Pharmacy & Life Sciences, 4(7).
8. Dasari, S., & Patra, A. K. (2015). Luminescent europium and terbium complexes of dipyridoquinoxaline and dipyridophenazine ligands as photosensitizing antennae: structures and biological perspectives. Dalton Transactions, 44(46), 19844-19855.

9. Dash, A., Pillai, M. R. A., & Knapp, F. F. (2015). Production of 177Lu for targeted radionuclide therapy: available options. Nuclear medicine and molecular imaging, 49(2), 85-107.
10. Demirkol, M. O., Kiremit, M. C., Acar, O., Falay, O., Ucar, B., & Esen, T. (2018). Local salvage treatment of post-brachytherapy recurrent prostate cancer via theranostic application of PSMA-labeled lutetium-177. Clinical genitourinary cancer, 16(2), 99-102.
11. Demirkol, M. O., Özkan, A., Uçar, B., Wester, H.-J., & Ferhanoğlu, B. (2021). Extramedullary Relapsed Multiple Myeloma Treatment With 177Lu-Labeled CXCR4 Endoradiotherapy and Dosimetric Results. Clinical nuclear medicine.
12. Gibellini, F., & Smith, T. K. (2010). The Kennedy pathway—de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB life, 62(6), 414-428.
13. Glunde, K., Bhujwalla, Z. M., & Ronen, S. M. (2011). Choline metabolism in malignant transformation. Nature Reviews Cancer, 11(12), 835-848.
14. Greiser, J., Weigand, W., & Freesmeyer, M. (2019). Metal-based complexes as Pharmaceuticals for Molecular Imaging of the liver. Pharmaceuticals, 12(3), 137.
15. Han, G., Deng, Y., Sun, J., Ling, J., & Shen, Z. (2015). Research into europium complexes as magnetic resonance imaging contrast agents. Experimental and Therapeutic Medicine, 9(5), 1561-1566.
16. Higdon, J., Drake, V., Delage, B., & Stocker, R. (2000). Linus Pauling Institute Micronutrient Information Center. Oregon State University (2003–2018).
17. Khanal, S., Adhikari, U., Rijal, N. P., Bhattarai, S. R., Sankar, J., & Bhattarai, N. (2016). pH-responsive PLGA nanoparticle for controlled payload delivery of diclofenac sodium. Journal of functional biomaterials, 7(3), 21.
18. Kierkowicz, M., González-Domínguez, J. M., Pach, E., Sandoval, S., Ballesteros, B., Da Ros, T., & Tobias, G. (2017). Filling single-walled carbon nanotubes with lutetium chloride: A sustainable production of nanocapsules free of nonencapsulated material. ACS Sustainable Chemistry & Engineering, 5(3), 2501-2508.
19. Kuang, Y., Salem, N., Corn, D. J., Erokwu, B., Tian, H., Wang, F., & Lee, Z. (2010). Transport and metabolism of radiolabeled choline in hepatocellular carcinoma. Molecular pharmaceutics, 7(6), 2077-2092.
20. Lau, J. K. C., Zhang, X., & Yu, J. (2017). Animal models of non‐alcoholic fatty liver disease: current perspectives and recent advances. The Journal of pathology, 241(1), 36-44.
21. Liu, Z.-Y., Yishake, D., Fang, A.-P., Zhang, D.-M., Liao, G.-C., Tan, X.-Y., . . . Zhu, H.-L. (2020). Serum choline is associated with hepatocellular carcinoma survival: a prospective cohort study. Nutrition & metabolism, 17(1), 1-9.
22. Llovet, J. M., Castet, F., Heikenwalder, M., Maini, M. K., Mazzaferro, V., Pinato, D. J., . . . Finn, R. S. (2022). Immunotherapies for hepatocellular carcinoma. Nature Reviews Clinical Oncology, 19(3), 151-172.
23. Makadia, H. K., & Siegel, S. J. (2011). Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers, 3(3), 1377-1397.
24. Marcolin, É., Forgiarini, L. F., Tieppo, J., Dias, A. S., Freitas, L. A. R. d., & Marroni, N. P. (2011). Methionine-and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis. Arquivos de gastroenterologia, 48, 72-79.
25. Mehedint, M. G., & Zeisel, S. H. (2013). Choline’s role in maintaining liver function: new evidence for epigenetic mechanisms. Current opinion in clinical nutrition and metabolic care, 16(3), 339.
26. NORD. (2017). Rare Disease Information / Hepatocellular Carcinoma. Retrieved from https://rarediseases.org/rare-diseases/hepatocellular-carcinoma/
27. O’Dwyer, C., Yaworski, R., Katsumura, S., Ghorbani, P., Gobeil Odai, K., Nunes, J. R., . . . Han, S. (2020). Hepatic Choline Transport Is Inhibited During Fatty Acid–Induced Lipotoxicity and Obesity. Hepatology communications, 4(6), 876-889. Özkan, A., Uçar, B., Seymen, H., Yarar, Y. Y., Falay, F. O., & Demirkol, M. O. (2020). Posttherapeutic critical organ dosimetry of extensive 177Lu-PSMA inhibitor therapy with metastatic castration-resistant prostate cancer: one center results. Clinical nuclear medicine, 45(4), 288-291.
28. Petrouleas, V., Lemmon, R., & Christensen, A. (1978). X‐ray diffraction study of choline chloride’s β form. The Journal of Chemical Physics, 68(5), 2243-2246.
29. Philips, C. A., Rajesh, S., Nair, D. C., Ahamed, R., Abduljaleel, J. K., & Augustine, P. (2021). Hepatocellular carcinoma in 2021: an exhaustive update. Cureus, 13(11).
30. Scimeca, M., Bischetti, S., Lamsira, H. K., Bonfiglio, R., & Bonanno, E. (2018). Energy Dispersive X-ray (EDX) microanalysis: A powerful tool in biomedical research and diagnosis. European journal of histochemistry: EJH, 62(1).
31. Seju, U., Kumar, A., & Sawant, K. (2011). Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies. Acta biomaterialia, 7(12), 4169-4176.
32. Sivrikaya, S. (2019). A novel vortex-assisted liquid phase microextraction method for parabens in cosmetic oil products using deep eutectic solvent. International Journal of Environmental Analytical Chemistry, 99(15), 1575-1585.
33. Snehalatha, M., Venugopal, K., Saha, R. N., Babbar, A. K., & Sharma, R. K. (2008). Etoposide loaded PLGA and PCL nanoparticles II: biodistribution and pharmacokinetics after radiolabeling with Tc-99m. Drug delivery, 15(5), 277-287.
34. Tikhonova, T. N., Shirshin, E. A., Budylin, G. S., Fadeev, V. V., & Petrova, G. P. (2014). Assessment of the europium (III) binding sites on albumin using fluorescence spectroscopy. The Journal of Physical Chemistry B, 118(24), 6626-6633.
35. Tosyali, O. A., Allahverdiyev, A., Bagirova, M., Abamor, E. S., Aydogdu, M., Dinparvar, S., . . . Derman, S. (2021). Nano-co-delivery of lipophosphoglycan with soluble and autoclaved leishmania antigens into PLGA nanoparticles: Evaluation of in vitro and in vivo immunostimulatory effects against visceral leishmaniasis. Materials Science and Engineering: C, 120, 111684.
36. Ucar, B. (2019). Synthesis and characterization of natural lanthanum labelled DOTA-Peptides for simulating radioactive Ac-225 labeling. Applied Radiation and Isotopes, 153, 108816.
37. Ucar, B., & Acar, T. (2021). Macroaggregated Albumin (MAA): Production, Size Optimization, Eu (III) and Tb (III) Complexes. Journal of the Turkish Chemical Society Section A: Chemistry, 8(1), 209-216.
38. Ullah, R., Atilhan, M., Anaya, B., Khraisheh, M., García, G., ElKhattat, A., . . . Aparicio, S. (2015). A detailed study of cholinium chloride and levulinic acid deep eutectic solvent system for CO 2 capture via experimental and molecular simulation approaches. Physical Chemistry Chemical Physics, 17(32), 20941-20960.
39. WHO. (2020). International Agency for Research on Cancer, Estimated number of new cases in 2020, all cancers, both sexes, all ages.
40. Willyard, C. E., & Kalathil, S. C. (2020). Nuclear Medicine Liver/Spleen Test.
41. Yazar, S., Arvas, M. B., & Sahin, Y. (2022). Hydrothermal Synthesis of Flexible Fe‐Doped Polyaniline/Dye‐Functionalized Carbon Felt Electrode for Supercapacitor Applications. ChemistrySelect, 7(21), e202200016.