Optimized Rutin-incorporating PEGylated Nanoliposomes as a Model with Remarkable Selectivity Against PANC1 and MCF7 Cell Lines


Дәйексөз келтіру

Толық мәтін

Аннотация

Background:This study aims to enhance the delivery of polyphenols using nanotechnology.

Objective:To develop and evaluate liposomal formulations for improved delivery and stability of polyphenols, specifically focusing on Rutin.

Methods:Liposomal formulations were meticulously prepared via the Thin-Film Hydration method. Comprehensive physical characterization was conducted, including stability assessments using Dynamic Light Scattering (DLS) and Thermogravimetric Analysis (TGA). The free radical scavenging activity was measured using the DPPH• assay, and MTT cell viability assays were performed to assess anti-proliferative effects.

Results:The results demonstrated a significant reduction in nanoparticle size from 123 nm to 116 nm and an increase in charge from -14 to -22 with rising Rutin concentrations. The formulation achieved enhanced homogeneity at a Rutin concentration of 2.0 mg/mL and showed higher stability. Incorporating Rutin improved the formulation's stability over 30 days, as evidenced by a decrease in the Differential Scanning Calorimetry peak temperature from 58.65°C to 54.42°C. Rutin-loaded and co-loaded nanoliposomes exhibited remarkable selectivity against PANC1 and MCF7 cell lines, with IC50 values of 2.13±0.35 μg/mL and 4.75±0.19 μg/mL, respectively.

Conclusion:PEGylated Rutin-loaded nanoliposomes offer a promising platform for biodegradable and biocompatible drug delivery systems, enhancing the bioavailability, solubility, and stability of the polyphenols.

Авторлар туралы

Ali Al-Samydai

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre,, Al-Ahliyya Amman University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Moath Al Qaraleh

Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University

Email: info@benthamscience.net

Lidia Al-Halaseh

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mutah University

Email: info@benthamscience.net

Maha Abu Hajleh

Department of Cosmetic Science, Pharmacological and Diagnostic Research Centre, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University

Email: info@benthamscience.net

Simone Carradori

Department of Pharmacy “G. d'Annunzio”, University of Chieti-Pescara

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Maryam Abdulmaged

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre,, Al-Ahliyya Amman University

Email: info@benthamscience.net

Rand Kareem

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University

Email: info@benthamscience.net

Hasanain Alzaidi

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University

Email: info@benthamscience.net

Mohamad Mousa

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre,, Al-Ahliyya Amman University

Email: info@benthamscience.net

Yusuf Al-Hiari

Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan

Email: info@benthamscience.net

Hamdi Nsairat

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University

Email: info@benthamscience.net

Walhan Alshaer

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharmacological and Diagnostic Research Centre, Al-Ahliyya Amman University

Email: info@benthamscience.net

Әдебиет тізімі

  1. Hare, J.I.; Lammers, T.; Ashford, M.B.; Puri, S.; Storm, G.; Barry, S.T. Challenges and strategies in anti-cancer nanomedicine development: An industry perspective. Adv. Drug Deliv. Rev., 2017, 108, 25-38. doi: 10.1016/j.addr.2016.04.025 PMID: 27137110
  2. Santos, V.G.; Garcia, C.R.; Moreno, P.E.; Serrano Padilla, A.E.; Plascencia Salcedo, J.C. Central nervous system miliary brain metastasis secondary to breast cancer. Cureus, 2020, 12(8), e9649. doi: 10.7759/cureus.9649 PMID: 32923249
  3. Rahib, L.; Smith, B.D.; Aizenberg, R.; Rosenzweig, A.B.; Fleshman, J.M.; Matrisian, L.M. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res., 2014, 74(11), 2913-2921. doi: 10.1158/0008-5472.CAN-14-0155 PMID: 24840647
  4. Dela Cruz, C.S.; Tanoue, L.T.; Matthay, R.A. Lung cancer: Epidemiology, etiology, and prevention. Clin. Chest Med., 2011, 32(4), 605-644. doi: 10.1016/j.ccm.2011.09.001 PMID: 22054876
  5. Vishvakrama, P.; Sharma, S. Liposomes: An overview. J. Drug Deliv. Ther., 2014, 4(Suppl 3), 47-55.
  6. Romani, A.; Ieri, F.; Urciuoli, S.; Noce, A.; Marrone, G.; Nediani, C.; Bernini, R. Health effects of phenolic compounds found in extra-virgin olive oil, by-products, and leaf of Olea europaea L. Nutrients, 2019, 11(8), 1776. doi: 10.3390/nu11081776 PMID: 31374907
  7. Ruzzolini, J.; Chioccioli, S.; Monaco, N.; Peppicelli, S.; Andreucci, E.; Urciuoli, S.; Romani, A.; Luceri, C.; Tortora, K.; Calorini, L.; Caderni, G.; Nediani, C.; Bianchini, F. Oleuropein-rich leaf extract as a broad inhibitor of tumour and macrophage INOS in an Apc mutant rat model. Antioxidants, 2021, 10(10), 1577. doi: 10.3390/antiox10101577 PMID: 34679712
  8. Tresserra-Rimbau, A.; Arranz, S.; Vallverdu-Queralt, A. Dietary polyphenols in the prevention of stroke. Oxid. Med. Cell Longev., 2017, 2017, 7467962. doi: 10.1155/2017/7467962
  9. Albogami, S.; Hassan, A. Assessment of the efficacy of olive leaf (Olea europaea L.) extracts in the treatment of colorectal cancer and prostate cancer using in vitro cell models. Molecules, 2021, 26(13), 4069. doi: 10.3390/molecules26134069 PMID: 34279409
  10. Ahmad Farooqi, A.; Fayyaz, S.; Silva, A.; Sureda, A.; Nabavi, S.; Mocan, A.; Nabavi, S.; Bishayee, A. Oleuropein and cancer chemoprevention: The link is hot. Molecules, 2017, 22(5), 705. doi: 10.3390/molecules22050705 PMID: 28468276
  11. Ciafardini, G.; Marsilio, V.; Lanza, B.; Pozzi, N. Hydrolysis of oleuropein by Lactobacillus plantarum strains associated with olive fermentation. Appl. Environ. Microbiol., 1994, 60(11), 4142-4147. doi: 10.1128/aem.60.11.4142-4147.1994 PMID: 16349442
  12. Rishmawi, S.; Haddad, F.; Dokmak, G.; Karaman, R. A comprehensive review on the anti-cancer effects of oleuropein. Life (Basel), 2022, 12(8), 1140. doi: 10.3390/life12081140 PMID: 36013319
  13. Rahiman, S.; El-Metwally, T.H.; Shrivastava, D.; Tantry, M.N.; Tantry, B.A. Oleuropein and oleic acid: A novel emerging dietary target for human chronic diseases. Indian J. Biochem. Biophys., 2019, 56(4), 263-268.
  14. Ruzzolini, J.; Peppicelli, S.; Andreucci, E.; Bianchini, F.; Scardigli, A.; Romani, A.; La Marca, G.; Nediani, C.; Calorini, L. Oleuropein, the main polyphenol of Olea europaea leaf extract, has an anti-cancer effect on human BRAF melanoma cells and potentiates the cytotoxicity of current chemotherapies. Nutrients, 2018, 10(12), 1950. doi: 10.3390/nu10121950 PMID: 30544808
  15. Moran, J.M.; Leal-Hernandez, O.; Canal-Macias, M.L.; Roncero-Martin, R.; Guerrero-Bonmatty, R.; Aliaga, I.; Zamorano, J.D.P. Antiproliferative properties of oleuropein in human osteosarcoma cells. Nat. Prod. Commun., 2016, 11(4) doi: 10.1177/1934578X1601100418
  16. Sharma, S.; Ali, A.; Ali, J.; Sahni, J.K.; Baboota, S. Rutin: Therapeutic potential and recent advances in drug delivery. Expert Opin. Investig. Drugs, 2013, 22(8), 1063-1079. doi: 10.1517/13543784.2013.805744 PMID: 23795677
  17. Kubatka, P.; Mazurakova, A.; Samec, M.; Koklesova, L.; Zhai, K.; AL-Ishaq, R.; Kajo, K.; Biringer, K.; Vybohova, D.; Brockmueller, A.; Pec, M.; Shakibaei, M.; Giordano, F.A.; Büsselberg, D.; Golubnitschaja, O. Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression—3PM pathways. EPMA J., 2021, 12(4), 559-587. doi: 10.1007/s13167-021-00257-y PMID: 34950252
  18. Pandey, P.; Khan, F.; Qari, H.A.; Oves, M. Rutin (Bioflavonoid) as cell signaling pathway modulator: Prospects in treatment and chemoprevention. Pharmaceuticals (Basel), 2021, 14(11), 1069. doi: 10.3390/ph14111069 PMID: 34832851
  19. Markopoulos, C.; Vertzoni, M.; Agalias, A.; Magiatis, P.; Reppas, C. Stability of oleuropein in the human proximal gut. J. Pharm. Pharmacol., 2010, 61(2), 143-149. doi: 10.1211/jpp.61.02.0002 PMID: 19178760
  20. Gullón, B.; Lú-Chau, T.A.; Moreira, M.T.; Lema, J.M.; Eibes, G. Rutin: A review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability. Trends Food Sci. Technol., 2017, 67, 220-235. doi: 10.1016/j.tifs.2017.07.008
  21. Gunasekaran, T.; Haile, T.; Nigusse, T.; Dhanaraju, M.D. Nanotechnology: An effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac. J. Trop. Biomed., 2014, 4(Suppl. 1), S1-S7. doi: 10.12980/APJTB.4.2014C980 PMID: 25183064
  22. Abu Hajleh, M.N.; Abu-Huwaij, R.; AL-Samydai, A.; Al-Halaseh, L.K.; Al-Dujaili, E.A. The revolution of cosmeceuticals delivery by using nanotechnology: A narrative review of advantages and side effects. J. Cosmet. Dermatol., 2021, 20(12), 3818-3828. doi: 10.1111/jocd.14441 PMID: 34510691
  23. Tsarbopoulos, A.; Gikas, E.; Papadopoulos, N.; Aligiannis, N.; Kafatos, A. Simultaneous determination of oleuropein and its metabolites in plasma by high-performance liquid chromatography. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 785(1), 157-164. doi: 10.1016/S1570-0232(02)00905-4 PMID: 12535848
  24. Kuntić, V.; Pejić, N.; Ivković, B.; Vujić, Z.; Ilić, K.; Mićić, S.; Vukojević, V. Isocratic RP-HPLC method for rutin determination in solid oral dosage forms. J. Pharm. Biomed. Anal., 2007, 43(2), 718-721. doi: 10.1016/j.jpba.2006.07.019 PMID: 16920326
  25. Al-Samydai, A.; Alshaer, W.; Al-Dujaili, E.A.S.; Azzam, H.; Aburjai, T. Preparation, characterization, and anticancer effects of capsaicin-loaded nanoliposomes. Nutrients, 2021, 13(11), 3995. doi: 10.3390/nu13113995 PMID: 34836251
  26. Ansari, M.; Kazemipour, M.; Fathi, S. Development of a simple green extraction procedure and HPLC method for determination of oleuropein in olive leaf extract applied to a multi-source comparative study. J. Indian Chem. Soc., 2011, 8, 38-47.
  27. Lu, M.; Qiu, Q.; Luo, X.; Liu, X.; Sun, J.; Wang, C.; Lin, X.; Deng, Y.; Song, Y. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian J. Pharm. Sci., 2019, 14(3), 265-274. doi: 10.1016/j.ajps.2018.05.011 PMID: 32104457
  28. Alshaer, W.; Zraikat, M.; Amer, A.; Nsairat, H.; Lafi, Z.; Alqudah, D.A.; Al Qadi, E.; Alsheleh, T.; Odeh, F.; Alkaraki, A.; Zihlif, M.; Bustanji, Y.; Fattal, E.; Awidi, A. Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: In vitro anti-proliferative and anti-invasive activity in glioblastoma. RSC Advances, 2019, 9(53), 30976-30988. doi: 10.1039/C9RA05636J PMID: 35529392
  29. Zhu, Y.; Wang, M.; Zhang, J.; Peng, W.; Firempong, C.K.; Deng, W.; Wang, Q.; Wang, S.; Shi, F.; Yu, J.; Xu, X.; Zhang, W. Improved oral bioavailability of capsaicin via liposomal nanoformulation: Preparation, in vitro drug release and pharmacokinetics in rats. Arch. Pharm. Res., 2015, 38(4), 512-521. doi: 10.1007/s12272-014-0481-7 PMID: 25231341
  30. Patel, R.B.; Solorio, L.; Wu, H.; Krupka, T.; Exner, A.A. Effect of injection site on in situ implant formation and drug release in vivo. J. Control. Release, 2010, 147(3), 350-358. doi: 10.1016/j.jconrel.2010.08.020 PMID: 20728486
  31. Ashar, F.; Hani, U.; Osmani, R.A.M.; Kazim, S.M.; Selvamuthukumar, S. Preparation and optimization of ibrutinib-loaded nanoliposomes using response surface methodology. Polymers (Basel), 2022, 14(18), 3886. doi: 10.3390/polym14183886 PMID: 36146030
  32. Pan, L.; Wang, H.; Gu, K. Nanoliposomes as vehicles for astaxanthin: Characterization, in vitro release evaluation and structure. Molecules, 2018, 23(11), 2822. doi: 10.3390/molecules23112822 PMID: 30380797
  33. Matusiewicz, M.; Kosieradzka, I.; Niemiec, T.; Grodzik, M.; Antushevich, H.; Strojny, B.; Gołębiewska, M. In vitro influence of extracts from snail Helix aspersa Müller on the colon cancer cell line Caco-2. Int. J. Mol. Sci., 2018, 19(4), 1064. doi: 10.3390/ijms19041064 PMID: 29614018
  34. Hong, B.; Xue, P.; Wu, Y.; Bao, J.; Chuah, Y.J.; Kang, Y. A concentration gradient generator on a paper-based microfluidic chip coupled with cell culture microarray for high-throughput drug screening. Biomed. Microdevices, 2016, 18(1), 21. doi: 10.1007/s10544-016-0054-2 PMID: 26864970
  35. Maki, M.A.A.; Kumar, P.V.; Cheah, S.C.; Siew Wei, Y.; Al-Nema, M.; Bayazeid, O.; Majeed, A.B.B.A. Molecular modeling-based delivery system enhances everolimus-induced apoptosis in CaCo2 cells. ACS Omega, 2019, 4(5), 8767-8777. doi: 10.1021/acsomega.9b00109 PMID: 31459966
  36. Al-Nema, M.; Gaurav, A.; Lee, M.T.; Okechukwu, P.; Nimmanpipug, P.; Lee, V.S. Evaluation of the acute oral toxicity and antipsychotic activity of a dual inhibitor of PDE1B and PDE10A in rat model of schizophrenia. PLoS One, 2022, 17(12), e0278216. doi: 10.1371/journal.pone.0278216 PMID: 36454774
  37. Cristiano, M.C.; Barone, A.; Mancuso, A.; Torella, D.; Paolino, D. Rutin-loaded nanovesicles for improved stability and enhanced topical efficacy of natural compound. J. Funct. Biomater., 2021, 12(4), 74. doi: 10.3390/jfb12040074 PMID: 34940553
  38. Kızılbey, K. Optimization of rutin-loaded PLGA nanoparticles synthesized by single-emulsion solvent evaporation method. ACS Omega, 2019, 4(1), 555-562. doi: 10.1021/acsomega.8b02767
  39. Zhang, S.; Han, Y. Preparation, characterisation and antioxidant activities of rutin-loaded zein-sodium caseinate nanoparticles. PLoS One, 2018, 13(3), e0194951. doi: 10.1371/journal.pone.0194951 PMID: 29579133
  40. Al-Ekaid, N.M.; Al-Samydai, A.; Al-deeb, I.; Nsairat, H.; Khleifat, K.; Alshaer, W. Preparation, characterization, and anticancer activity of pegylated nano liposomal loaded with rutin against human carcinoma cells (HT‐29). Chem. Biodivers., 2023, 20(11), e202301167. doi: 10.1002/cbdv.202301167 PMID: 37781742
  41. Mahmood, T.H.; Al-Samydai, A.; Sulaibi, M.A.; Alqaraleh, M.; Abed, A.I.; Shalan, N.; Alsanabrah, A.; Alsotari, S.T.; Nsairat, H.; Alshaer, W. Development of pegylated nano‐phytosome formulation with oleuropein and rutin to compare anti‐colonic cancer activity with Olea europaea leaves extract. Chem. Biodivers., 2023, 20(8), e202300534. doi: 10.1002/cbdv.202300534 PMID: 37498138
  42. Abu Hajleh, M.N.; Al-limoun, M.; Al-Tarawneh, A.; Hijazin, T.J.; Alqaraleh, M.; Khleifat, K.; Al-Madanat, O.Y.; Qaisi, Y.A.; AlSarayreh, A.; Al-Samydai, A.; Qaralleh, H.; Al-Dujaili, E.A.S. Synergistic effects of AgNPs and biochar: A potential combination for combating lung cancer and pathogenic bacteria. Molecules, 2023, 28(12), 4757. doi: 10.3390/molecules28124757 PMID: 37375312
  43. Morgan, A.B.; Mukhopadhyay, P. A targeted review of bio-derived plasticizers with flame retardant functionality used in PVC. J. Mater. Sci., 2022, 57(14), 7155-7172. doi: 10.1007/s10853-022-07096-w
  44. Alper Öztürk, A.; Başaran, E.; Şenel, B.; Demirel, M.; Sarıca, Ş. Synthesis, characterization, antioxidant activity of Quercetin, Rutin and Quercetin-Rutin incorporated β-cyclodextrin inclusion complexes and determination of their activity in NIH-3T3, MDA-MB-231 and A549 cell lines. J. Mol. Struct., 2023, 1282, 135169. doi: 10.1016/j.molstruc.2023.135169
  45. Prasad, R.; Prasad, S.B. A review on the chemistry and biological properties of Rutin, a promising nutraceutical agent. Asian J. Pharm. Pharmacol., 2019, 5(S1), 1-20. doi: 10.31024/ajpp.2019.5.s1.1
  46. Kalaydina, R.V.; Bajwa, K.; Qorri, B.; DeCarlo, A.; Szewczuk, M.R. Recent advances in “smart” delivery systems for extended drug release in cancer therapy. Int. J. Nanomed., 2018, 13, 4727-4745. doi: 10.2147/IJN.S168053 PMID: 30154657
  47. Xu, G.; Gu, H.; Hu, B.; Tong, F.; Liu, D.; Yu, X.; Zheng, Y.; Gu, J. PEG-b-(PELG-g-PLL) nanoparticles as TNF-α nanocarriers: Potential cerebral ischemia/reperfusion injury therapeutic applications. Int. J. Nanomed., 2017, 12, 2243-2254. doi: 10.2147/IJN.S130842 PMID: 28356740
  48. Nouri, Z.; Fakhri, S.; Nouri, K.; Wallace, C.E.; Farzaei, M.H.; Bishayee, A. Targeting multiple signaling pathways in cancer: The rutin therapeutic approach. Cancers (Basel), 2020, 12(8), 2276. doi: 10.3390/cancers12082276 PMID: 32823876
  49. Vieira, N.F.; Serafini, L.N.; Novais, P.C.; Neto, F.S.L.; Cirino, M.L.A.; Kemp, R.; Ardengh, J.C.; Saggioro, F.P.; Gaspar, A.F.; Sankarankutty, A.K.; Júnior, J.R.L.; Tirapelli, D.P.C.; dos Santos, J.S. The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis. Oncotarget, 2021, 12(17), 1638-1650. doi: 10.18632/oncotarget.28038 PMID: 34434493
  50. Danaei, M.; Dehghankhold, M.; Ataei, S.; Hasanzadeh Davarani, F.; Javanmard, R.; Dokhani, A.; Khorasani, S.; Mozafari, M.R. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 2018, 10(2), 57. doi: 10.3390/pharmaceutics10020057 PMID: 29783687
  51. Satari, A.; Ghasemi, S.; Habtemariam, S.; Asgharian, S.; Lorigooini, Z. Rutin: A flavonoid as an effective sensitizer for anticancer therapy; insights into multifaceted mechanisms and applicability for combination therapy. Evid. Based Complement. Alternat. Med., 2021, 2021, 9913179. doi: 10.1155/2021/9913179
  52. Pinzaru, I.; Chioibas, R.; Marcovici, I.; Coricovac, D.; Susan, R.; Predut, D.; Georgescu, D.; Dehelean, C. Rutin exerts cytotoxic and senescence-inducing properties in human melanoma cells. Toxics, 2021, 9(9), 226. doi: 10.3390/toxics9090226 PMID: 34564377
  53. Hua, S. Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery. Int. J. Nanomed., 2014, 9, 735-744. doi: 10.2147/IJN.S55805 PMID: 24511230
  54. Siddique, F.; Aqdas, A.; Bashir, M.; Nadeem, S.; Rawat, R.; Ahmad, S.; Anwaar, A.; Arora, R.; Kaur, M.; Gulati, M.; Yadav, S.; Vargas, C.; Cruz, D-L.; Swarnkar, S.; Gupta, P.; Wal, P.; Behl, T.; Ojha, S. Harnessing the potential of natural products in cancer treatment: A comprehensive review. J. Biol. Regul. Homeost. Agents, 2024, 38, 873-897.
  55. Fu, P.; Shi, P.; Li, X.; Li, W.; Li, H.; Wu, Z. One-pot synthesis of ultrasmall ferric ion coupled mitoxantrone nanoparticles for high bioavailability and effective chemo-ferroptosis combination therapy of breast cancer. J. Drug Deliv. Sci. Technol., 2024, 91, 105187. doi: 10.1016/j.jddst.2023.105187
  56. Whitnall, M.; Howard, J.; Ponka, P.; Richardson, D.R. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc. Natl. Acad. Sci. USA, 2006, 103(40), 14901-14906. doi: 10.1073/pnas.0604979103 PMID: 17003122
  57. Vetta, M.D.; González, L.; Nogueira, J.J. Hydrogen bonding regulates the rigidity of liposome‐encapsulated chlorin photosensitizers. ChemistryOpen, 2018, 7(6), 475-483. doi: 10.1002/open.201800050 PMID: 29938159
  58. Kerdudo, A.; Dingas, A.; Fernandez, X.; Faure, C. Encapsulation of rutin and naringenin in multilamellar vesicles for optimum antioxidant activity. Food Chem., 2014, 159, 12-19. doi: 10.1016/j.foodchem.2014.03.005 PMID: 24767021

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML

© Bentham Science Publishers, 2025