Yıl: 2022 Cilt: 19 Sayı: 1 Sayfa Aralığı: 84 - 92 Metin Dili: İngilizce DOI: 10.4274/tjps.galenos.2021.81905 İndeks Tarihi: 26-06-2022

The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization

Öz:
Objectives: Daidzein (DZ), a water-insoluble isoflavone, has many beneficial effects (anti-inflammatory, antioxidant, and anticancer effects, etc.) on human health. DZ has a very low oral bioavailability related to its physicochemical properties (low solubility, intense metabolism of DZ in the intestine and liver). This study aimed to prepare and in vitro characterize the nanosuspension formulations of DZ to improve the poor solubility and efficacy of DZ. Materials and Methods: DZ nanosuspension formulations were prepared with media milling technique using zirconium oxide beads as milling media. Pluronic F127 and polyvinylpyrrolidone (PVP) K30 (formulation A; F-A) and sodium dodecyl sulfate (SDS) (SDS + pluronic F127 + PVP K30; formulation B; F-B) were used as stabilizers. The nanosuspension formulations were evaluated for morphological properties, particle sizes, zeta potential, DZ content, saturation solubility, dissolution, and their cytotoxic effects on RG2 glioblastoma tumor cells. Results: F-A and F-B formulations were nanosized (in the range of about 181-235 nm) and had negative zeta potential values before and after lyophilization. The DZ content of F-A and F-B formulations were found to be 93.68±0.78% and 89.75±0.49%, respectively. Fourier transform infrared spectroscopy analysis showed that there was no significant interaction between DZ and the excipients. Differential scanning calorimetry and X-ray diffraction analyses confirmed no change in the crystal structure of DZ in F-A and F-B formulations. Conclusion: In this study, the nanosuspension formulations were successfully prepared and characterized in vitro. Nanosuspension formulations increased the saturation solubility, dissolution rate, and cytotoxic effect of DZ.
Anahtar Kelime:

Daidzein Nanosüspansiyon Formülasyonları: Hazırlanması ve İn Vitro Karakterizasyonu

Öz:
Amaç: Suda çözünmeyen bir izoflavon olan daidzein (DZ), insan sağlığı üzerinde pek çok faydalı etkiye (anti-inflamatuvar, antioksidan ve antikanser etkileri vb.) sahiptir. DZ, fizikokimyasal özelliklerine (düşük çözünürlük, bağırsakta ve karaciğerde DZ’nin yoğun metabolizasyonu) bağlı olarak çok düşük bir oral biyoyararlanıma sahiptir. Bu çalışmanın amacı, DZ’nin zayıf çözünürlüğünü ve etkinliğini iyileştirmek üzere DZ’nin nanosüspansiyon formülasyonunu hazırlamak ve in vitro olarak karakterize etmektir. Gereç ve Yöntemler: DZ nanosüspansiyon formülasyonları, öğütme ortamı olarak zirkonyum oksit boncukları kullanılarak yaş öğütme tekniği ile hazırlandı. Stabilizan olarak pluronic F127 ve polivinilpirolidon (PVP) K30 (formülasyon A; F-A) ve sodyum dodesil sülfat (SDS) (SDS + pluronic F127 + PVP K30; formülasyon B; F-B) kullanıldı. Nanosüspansiyon formülasyonları, morfolojik özellikleri, partikül boyutları, zeta potansiyel, DZ içeriği, doygunluk çözünürlüğü, çözünme ve RG2 glioblastoma tümör hücreleri üzerindeki sitotoksik etkileri açısından değerlendirildi. Bulgular: Liyofilizasyon öncesi ve sonrası, F-A ve F-B formülasyonları nano-boyutluydular (yaklaşık 181-235 nm aralığında) ve ayrıca negatif zeta potansiyel değerlerine sahiptiler. F-A ve F-B formülasyonlarının DZ içeriği sırasıyla; %93,68±0,78 ve %89,75±0,49 olarak bulundu. Fourier dönüşümlü kızılötesi analizi, DZ ve yardımcı maddeler arasında önemli bir etkileşim olmadığını gösterdi. Diferansiyel taramalı kalorimetre ve X-ışını difraktometresi analizleri, F-A ve F-B formülasyonlarında DZ’nin kristal yapısında hiçbir değişiklik olmadığını doğruladı. Sonuç: Bu çalışmada, nanosüspansiyon formülasyonları başarıyla hazırlandı ve in vitro olarak karakterize edildi. Nanosüspansiyon formülasyonları DZ’nin doygunluk çözünürlüğünü, çözünme hızını ve sitotoksik etkisini artırdı
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Thadkala K, Nanam PK, Rambabu B, Sailu C, Aukunuru J. Preparation and characterization of amorphous ezetimibe nanosuspensions intended for enhancement of oral bioavailability. Int J Pharm Investig. 2014;4:131-137.
  • 2. Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015;10:13-23.
  • 3. Wang Y, Zheng Y, Zhang L, Wang Q, Zhang D. Stability of nanosuspensions in drug delivery. J Control Release. 2013;172:1126-1141.
  • 4. Jethara SI, Patel MR, Patel AD. Nano suspension drug delivery system: an overview. Aperito J Drug Design Pharmacol. 2014;1:106.
  • 5. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012;2012:195727.
  • 6. Patel HM, Patel BB, Shah CN. Nanosuspension: a novel approach to enhance solubility of poorly water soluble drugs - a review. Int J Adv Pharm. 2016;5:21-29.
  • 7. Bektaş AE, Uğur AB, Çetin M. Nanosuspensions: preparation methods and stability ıssue. Hacettepe Univ J Fac Pharm. 2018;38:85-101.
  • 8. Verma S, Kumar S, Gokhale R, Burgess DJ. Physical stability of nanosuspensions: investigation of the role of stabilizers on Ostwald ripening. Int J Pharm. 2011;406:145-152.
  • 9. Jacob S, Nair AB, Shah J. Emerging role of nanosuspensions in drug delivery systems. Biomater Res. 2020;24:3.
  • 10. Ugur Kaplan AB, Cetin M, Orgul D, Taghizadehghalehjoughi A, Hacımuftuoglu A, Hekimoglu S. Formulation and in vitro evaluation of topical nanoemulsion and nanoemulsion-based gels containing daidzein. J Drug Deliv Sci Technol. 2019;52:189-203.
  • 11. Ma Y, Zhao X, Li J, Shen Q. The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability. Int J Nanomedicine. 2012;7:559-570.
  • 12. Gao Y, Gu W, Chen L, Xu Z, Li Y. The role of daidzein-loaded sterically stabilized solid lipid nanoparticles in therapy for cardio-cerebrovascular diseases. Biomaterials. 2008;29:4129-4136.
  • 13. Zhang Z, Huang Y, Gao F, Bu H, Gu W, Li Y. Daidzein-phospholipid complex loaded lipid nanocarriers improved oral absorption: in vitro characteristics and in vivo behavior in rats. Nanoscale. 2011;3:1780-1787.
  • 14. Lo FH, Mak NK, Leung KN. Studies on the anti-tumor activities of the soy isoflavone daidzein on murine neuroblastoma cells. Biomed Pharmacother. 2007;61:591-595.
  • 15. Guo JM, Kang GZ, Xiao BX, Liu DH, Zhang S. Effect of daidzein on cell growth, cell cycle, and telomerase activity of human cervical cancer in vitro. Int J Gynecol Cancer. 2004;14:882-888.
  • 16. Siegelin MD, Gaiser T, Habel A, Siegelin Y. Daidzein overcomes TRAIL- resistance in malignant glioma cells by modulating the expression of the intrinsic apoptotic inhibitor, bcl-2. Neurosci Lett. 2009;454:223-228.
  • 17. Gundogdu G, Dodurga Y, Cetin M, Secme M, Cicek B. The cytotoxic and genotoxic effects of daidzein on MIA PaCa-2 human pancreatic carcinoma cells and HT-29 human colon cancer cells. Drug Chem Toxicol. 2020;43:581-587.
  • 18. Qiu F, Chen XY, Song B, Zhong DF, Liu CX. Influence of dosage forms on pharmacokinetics of daidzein and its main metabolite daidzein-7-O- glucuronide in rats. Acta Pharmacol Sin. 2005;26:1145-1152.
  • 19. Borghetti GS, Pinto AP, Lula IS, Sinisterra RD, Teixeira HF, Bassai VL. Daidzein/cyclodextrin/hydrophilic polymer ternary systems. Drug Dev Ind Pharm. 2011;37:886-893.
  • 20. Ge YB, Chen DW, Xie LP, Zhang RQ. Optimized preparation of daidzein- loaded chitosan microspheres and in vivo evaluation after intramuscular injection in rats. Int J Pharm. 2007;338:142-151.
  • 21. Bhalla Y, Chadha K, Chadha R, Karan M. Daidzein cocrystals: an opportunity to improve its biopharmaceutical parameters. Heliyon. 2019;5:e02669.
  • 22. Romano-Feinholz S, Salazar-Ramiro A, Muñoz-Sandoval E, Magaña- Maldonado R, Hernández Pedro N, Rangel López E, González Aguilar A, Sánchez García A, Sotelo J, Pérez de la Cruz V, Pineda B. Cytotoxicity induced by carbon nanotubes in experimental malignant glioma. Int J Nanomed. 2017;12:6005-6026.
  • 23. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10:57.
  • 24. Zhang X, Liu X, Zhang J, Zhou W, Lu J, Wang Q, Hu R. Daidzein derivative daid002 inhibits glioblastoma growth via disrupting the interaction between moesin and CD44. Oncotarget. 2018;5:1-12.
  • 25. Patel VR, Agrawal YK. Nanosuspension: an approach to enhance solubility of drugs. J Adv Pharm Technol Res. 2011;2:81-87.
  • 26. Attari Z, Kalvakuntla S, Reddy MS, Deshpande M, Rao CM, Koteshwara KB. Formulation and characterisation of nanosuspensions of BCS class II and IV drugs by combinative method. J Exp Nanosci. 2016;11:276-288.
  • 27. Sharma M, Mehta I. Surface stabilized atorvastatin nanocrystals with improved bioavailability, safety and antihyperlipidemic potential. Sci Rep. 2019;9:16105.
  • 28. Shah U, Joshi G, Sawant K. Improvement in antihypertensive and antianginal effects of felodipine by enhanced absorption from PLGA nanoparticles optimized by factorial design. Mater Sci Eng C Mater Biol Appl. 2014;35:153-163.
  • 29. Kandilli B, Ugur Kaplan AB, Cetin M, Taspinar N, Ertugrul MS, Aydin IC, Hacimuftuoglu A. Carbamazepine and levetiracetam- loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies. Drug Dev Ind Pharm. 2020;46:1063- 1072.
  • 30. Honary S, Zahir F. Effect of zeta potential on the properties of nano-drug delivery systems - a review (Part 2). Trop J Pharm Res. 2013;12:265-273.
  • 31. Scheithauer EC, Li W, Ding Y, Harhaus L, Roether JA, Boccaccini AR. Preparation and characterization of electrosprayed daidzein-loaded PHBV microspheres. Mater Lett. 2015;158:66-69.
  • 32. Daidzein, >99% | LC laboratories. Accessed date: 14, 2021. Available from: https://lclabs.com/products/d-2946-daidzein
  • 33. Huang Z, Xia J, Li J, Gao X, Wang Y, Shen Q. Optimization and bioavailability evaluation of self-microemulsifying drug delivery system of the daidzein–nicotinamide complex. RSC Advances. 2016;6:112686- 112694.
  • 34. Kalvakuntla S, Deshpande M, Attari Z, Kunnatur B K. Preparation and characterization of nanosuspension of aprepitant by H96 process. Adv Pharm Bull. 2016;6:83-90
  • 35. Panizzon GP, Giacomini Bueno F, Ueda-Nakamura T, Nakamura CV, Dias Filho BP. Manufacturing different types of solid dispersions of bcs class IV polyphenol (daidzein) by spray drying: formulation and bioavailability. Pharmaceutics. 2019;11:492.
  • 36. The United States Convention. United States Pharmacopeia (USP 30- NF25).; 2007.
  • 37. Silva AP, Nunes BR, De Oliveira MC, Koester LS, Mayorga P, Bassani VL, Teixeira HF. Development of topical nanoemulsions containing the isoflavone genistein. Pharmazie. 2009;64:32-35.
  • 38. Oliveira SR, Taveira SF, Marreto RN, Valadares MC, Diniz DGA, Lima EM. Preparation and characterization of solid oral dosage forms containing soy isoflavones. Rev Bras Farmacogn. 2013;23:175-181.
  • 39. Argenta DF, de Mattos CB, Misturini FD, Koester LS, Bassani VL, Simões CM, Teixeira HF. Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein. Int J Nanomed. 2014;9:4737-4747.
  • 40. Wang Q, Liu W, Wang J, Liu H, Chen Y. Preparation and pharmacokinetic study of daidzein long-circulating liposomes. Nanoscale Res Lett. 2019;14:321.
  • 41. Wang H, Xiao Y, Wang H, Sang Z, Han X, Ren S, Du R, Shi X, Xie Y. Development of daidzein nanosuspensions: preparation, characterization, in vitro evaluation, and pharmacokinetic analysis. Int J Pharm. 2019;566:67-76.
  • 42. Yao J, Cui B, Zhao X, Wang Y, Zeng Z, Sun C, Yang D, Liu G, Gao J, Cui H. Preparation, characterization, and evaluation of azoxystrobin nanosuspension produced by wet media milling. Appl Nanosci. 2018;8:297-307.
  • 43. Hu L, Zhang N, Yang G, Zhang J. Effects of tween-80 on the dissolution properties of daidzein solid dispersion in vitro. Int J Chem Int. J. Quantum Chem.. 2011;3(1):68-73.
  • 44. Farjadian S, Khaioei Neiad L, Fazeli M, Askari Firouziaei H, Zaeri S. Doxorubicin cytotoxicity in combination with soy isoflavone daidzein on MCF-7 breast cancer cells. Mal J Nutr. 2015;21:67-73.
  • 45. Pal R, Mamidi MK, Das AK, Bhonde R. Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells. Arch Toxicol. 2012;86:651-661.
APA KAPLAN A, Ozturk N, ÇETİN M, Vural I, OZNULUER OZER T (2022). The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. , 84 - 92. 10.4274/tjps.galenos.2021.81905
Chicago KAPLAN Afife Büşra UĞUR,Ozturk Naile,ÇETİN Meltem,Vural Imran,OZNULUER OZER Tuba The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. (2022): 84 - 92. 10.4274/tjps.galenos.2021.81905
MLA KAPLAN Afife Büşra UĞUR,Ozturk Naile,ÇETİN Meltem,Vural Imran,OZNULUER OZER Tuba The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. , 2022, ss.84 - 92. 10.4274/tjps.galenos.2021.81905
AMA KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. . 2022; 84 - 92. 10.4274/tjps.galenos.2021.81905
Vancouver KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. . 2022; 84 - 92. 10.4274/tjps.galenos.2021.81905
IEEE KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T "The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization." , ss.84 - 92, 2022. 10.4274/tjps.galenos.2021.81905
ISNAD KAPLAN, Afife Büşra UĞUR vd. "The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization". (2022), 84-92. https://doi.org/10.4274/tjps.galenos.2021.81905
APA KAPLAN A, Ozturk N, ÇETİN M, Vural I, OZNULUER OZER T (2022). The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. Turkish Journal of Pharmaceutical Sciences, 19(1), 84 - 92. 10.4274/tjps.galenos.2021.81905
Chicago KAPLAN Afife Büşra UĞUR,Ozturk Naile,ÇETİN Meltem,Vural Imran,OZNULUER OZER Tuba The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. Turkish Journal of Pharmaceutical Sciences 19, no.1 (2022): 84 - 92. 10.4274/tjps.galenos.2021.81905
MLA KAPLAN Afife Büşra UĞUR,Ozturk Naile,ÇETİN Meltem,Vural Imran,OZNULUER OZER Tuba The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. Turkish Journal of Pharmaceutical Sciences, vol.19, no.1, 2022, ss.84 - 92. 10.4274/tjps.galenos.2021.81905
AMA KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. Turkish Journal of Pharmaceutical Sciences. 2022; 19(1): 84 - 92. 10.4274/tjps.galenos.2021.81905
Vancouver KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization. Turkish Journal of Pharmaceutical Sciences. 2022; 19(1): 84 - 92. 10.4274/tjps.galenos.2021.81905
IEEE KAPLAN A,Ozturk N,ÇETİN M,Vural I,OZNULUER OZER T "The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization." Turkish Journal of Pharmaceutical Sciences, 19, ss.84 - 92, 2022. 10.4274/tjps.galenos.2021.81905
ISNAD KAPLAN, Afife Büşra UĞUR vd. "The Nanosuspension Formulations of Daidzein: Preparation and In Vitro Characterization". Turkish Journal of Pharmaceutical Sciences 19/1 (2022), 84-92. https://doi.org/10.4274/tjps.galenos.2021.81905