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image of QbD-driven Formulation Development and Evaluation of Genistein Nanoparticles for Prostate Cancer

Abstract

Background

Genistein (GEN) shows significant anticancer potential, particularly against prostate cancer. However, its clinical application is limited by poor water solubility, rapid metabolism and excretion, low bioavailability, and lack of targeted delivery to cancer cells, hindering its effectiveness as a chemopreventive or therapeutic agent.

Objective

In this study, poly-ε-caprolactone (PCL) nanoparticles incorporating polyvinyl alcohol (PVA) as a stabilizer were engineered to encapsulate genistein (GEN) effectively. Utilizing a Quality by Design (QbD) methodology, the development and optimization of these nanoparticles were systematically approached.

Methods

GEN-loaded PCL nanoparticles (NPs) were prepared using the Solvent Evaporation Technique, ideal for encapsulating hydrophobic drugs. A Plackett–Burman design (PBD) identified key factors, followed by a Box–Behnken design (BBD) to optimize nanoparticle quality. The NPs were evaluated for particle size, zeta potential (ZP), polydispersity index (PDI), morphology, encapsulation efficiency (EE), drug release, and cytotoxicity.

Results

The optimized formulation containing PCL, PVA, and Volume of organic solvent as 43.7 mg, 6.2 mg, and 10.0 ml, respectively was chosen because it showed EE (%) of 94.0%, average particle size of 150 nm, PDI of 0.10, ZP of -28.0 and exhibited sustained release of GEN for around four days. The antiproliferative activities of GEN PCL NPs were confirmed by the MTT test on malignant prostate carcinoma cell lines (PC3). Flow cytometric analysis showed that the inhibition of cell proliferation of more potent GEN PCL NPs is comparable with the effects of free GEN.

Conclusion

The findings indicate that genistein-loaded PCL nanoparticles have the potential to augment the anticancer efficacy of genistein, both and . This suggests their promise as a viable candidate for prostate cancer treatment.

© 2024 Bentham Science Publishers
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2024-10-28
2025-01-20

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References

  1. Zhao J. Zhang C. Wang W. Li C. Mu X. Hu K. Current progress of nanomedicine for prostate cancer diagnosis and treatment. Biomed. Pharmacother. 2022 155 113714 10.1016/j.biopha.2022.113714 36150309
    [Google Scholar]
  2. Siegel R.L. Miller K.D. Fuchs H.E. Jemal A. Cancer statistics, 2022. CA Cancer J. Clin. 2022 72 1 7 33 10.3322/caac.21708 35020204
    [Google Scholar]
  3. Shi J. Kantoff P.W. Wooster R. Farokhzad O.C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2017 17 1 20 37 10.1038/nrc.2016.108 27834398
    [Google Scholar]
  4. Olivas A. Price R.S. Obesity, Inflammation, and Advanced Prostate Cancer. Nutr. Cancer 2021 73 11-12 2232 2248 10.1080/01635581.2020.1856889 33287566
    [Google Scholar]
  5. Huang Y.T. Tseng N.C. Chen Y.K. Huang K.H. Lin H.Y. Huang Y.Y. Hwang T.I.S. Ou Y.C. The detection performance of 18F–prostate-specific membrane Antigen-1007 PET/CT in primary prostate cancer. Clin. Nucl. Med. 2022 47 9 755 762 10.1097/RLU.0000000000004228 35452013
    [Google Scholar]
  6. Sulaiman G.M. Waheeb H.M. Jabir M.S. Khazaal S.H. Dewir Y.H. Naidoo Y. Hesperidin loaded on gold nanoparticles as a drug delivery system for a successful biocompatible, anti-cancer, anti-inflammatory and phagocytosis inducer model. Sci. Rep. 2020 10 1 9362 10.1038/s41598‑020‑66419‑6 32518242
    [Google Scholar]
  7. Li Q.S. Li C.Y. Li Z.L. Zhu H.L. Genistein and its synthetic analogs as anticancer agents. Anticancer. Agents Med. Chem. 2012 12 3 271 281 10.2174/187152012800228788 22043996
    [Google Scholar]
  8. Ullah M.F. Ahmad A. Zubair H. Khan H.Y. Wang Z. Sarkar F.H. Hadi S.M. Soy isoflavone genistein induces cell death in breast cancer cells through mobilization of endogenous copper ions and generation of reactive oxygen species. Mol. Nutr. Food Res. 2011 55 4 553 559 10.1002/mnfr.201000329 21462322
    [Google Scholar]
  9. Hussain A. Harish G. Prabhu S.A. Mohsin J. Khan M.A. Rizvi T.A. Sharma C. Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression. Cancer Epidemiol. 2012 36 6 e387 e393 10.1016/j.canep.2012.07.005 22884883
    [Google Scholar]
  10. Li H.Q. Luo Y. Qiao C.H. The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. Mini Rev. Med. Chem. 2012 12 4 350 362 10.2174/138955712799829258 22303948
    [Google Scholar]
  11. Vodnik V.V. Mojić M. Stamenović U. Otoničar M. Ajdžanović V. Maksimović-Ivanić D. Mijatović S. Marković M.M. Barudžija T. Filipović B. Milošević V. Šošić-Jurjević B. Development of genistein-loaded gold nanoparticles and their antitumor potential against prostate cancer cell lines. Mater. Sci. Eng. C 2021 124 112078 10.1016/j.msec.2021.112078 33947570
    [Google Scholar]
  12. Wang G. Zhang D. Yang S. Wang Y. Tang Z. Fu X. Co-administration of genistein with doxorubicin-loaded polypeptide nanoparticles weakens the metastasis of malignant prostate cancer by amplifying oxidative damage. Biomater. Sci. 2018 6 4 827 835 10.1039/C7BM01201B 29480308
    [Google Scholar]
  13. Gao X. Wang B. Wei X. Men K. Zheng F. Zhou Y. Zheng Y. Gou M. Huang M. Guo G. Huang N. Qian Z. Wei Y. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer. Nanoscale 2012 4 22 7021 7030 10.1039/c2nr32181e 23044718
    [Google Scholar]
  14. Gong C. Deng S. Wu Q. Xiang M. Wei X. Li L. Gao X. Wang B. Sun L. Chen Y. Li Y. Liu L. Qian Z. Wei Y. Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials 2013 34 4 1413 1432 10.1016/j.biomaterials.2012.10.068 23164423
    [Google Scholar]
  15. Huang L. Chen H. Zheng Y. Song X. Liu R. Liu K. Zeng X. Mei L. Nanoformulation of d -α-tocopheryl polyethylene glycol 1000 succinate- b -poly( ε -caprolactone- ran -glycolide) diblock copolymer for breast cancer therapy. Integr. Biol. 2011 3 10 993 1002 10.1039/c1ib00026h 21938302
    [Google Scholar]
  16. Zhang H. Cui W. Bei J. Wang S. Preparation of poly(lactide-co-glycolide-co-caprolactone) nanoparticles and their degradation behaviour in aqueous solution. Polym. Degrad. Stabil. 2006 91 9 1929 1936 10.1016/j.polymdegradstab.2006.03.004
    [Google Scholar]
  17. Hans M.L. Lowman A.M. Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater. Sci. 2002 6 4 319 327 10.1016/S1359‑0286(02)00117‑1
    [Google Scholar]
  18. Troiano G. Nolan J. Parsons D. Van Geen Hoven C. Zale S. A quality by design approach to developing and manufacturing polymeric nanoparticle drug products. AAPS J. 2016 18 6 1354 1365 10.1208/s12248‑016‑9969‑z 27631558
    [Google Scholar]
  19. Soni G. Kale K. Shetty S. Gupta M.K. Yadav K.S. Quality by design (QbD) approach in processing polymeric nanoparticles loading anticancer drugs by high pressure homogenizer. Heliyon 2020 6 4 e03846 10.1016/j.heliyon.2020.e03846 32373744
    [Google Scholar]
  20. Hassan H. Adam S.K. Alias E. Meor Mohd Affandi M.M.R. Shamsuddin A.F. Basir R. Central composite design for formulation and optimization of solid lipid nanoparticles to enhance oral bioavailability of acyclovir. Molecules 2021 26 18 5432 10.3390/molecules26185432 34576904
    [Google Scholar]
  21. Rathod V.R. Shah D.A. Dave R.H. Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables. Drug Dev. Ind. Pharm. 2020 46 3 443 455 10.1080/03639045.2020.1724135 32037896
    [Google Scholar]
  22. Jain P. Mirza M.A. Reyaz E. Beg M.A. Selvapandiyan A. Hasan N. Naqvi A. Punnoth Poonkuzhi N. Kuruniyan M.S. Yadav H.N. Ahmad F.J. Iqbal Z. QbD-Assisted development and optimization of doxycycline hyclate- and hydroxyapatite-loaded nanoparticles for periodontal delivery. ACS Omega 2024 9 4 4455 4465 10.1021/acsomega.3c07092 38313517
    [Google Scholar]
  23. Tang J. Xu N. Ji H. Liu H. Wang Z. Wu L. Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment. Int. J. Nanomedicine 2011 6 2429 2435 22072878
    [Google Scholar]
  24. Bohrey S. Chourasiya V. Pandey A. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study. Nano Converg. 2016 3 1 3 10.1186/s40580‑016‑0061‑2 28191413
    [Google Scholar]
  25. Rybak E. Kowalczyk P. Czarnocka-Śniadała S. Wojasiński M. Trzciński J. Ciach T. Microfluidic-assisted formulation of ε-polycaprolactone nanoparticles and evaluation of their properties and in vitro cell uptake. Polymers (Basel) 2023 15 22 4375 10.3390/polym15224375 38006099
    [Google Scholar]
  26. Chen T. Xing F. Sun Y. Facile fabrication of TPGS-PCL polymeric nanoparticles for paclitaxel delivery to breast cancer: investigation of antiproliferation and apoptosis induction. J. Exp. Nanosci. 2024 19 1 2281938 10.1080/17458080.2023.2281938
    [Google Scholar]
  27. Amasya G. Badilli U. Aksu B. Tarimci N. Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion — Solvent evaporation method. Eur. J. Pharm. Sci. 2016 84 92 102 10.1016/j.ejps.2016.01.003 26780593
    [Google Scholar]
  28. Laime-Oviedo L.A. Arenas-Chávez C.A. Yáñez J.A. Vera-Gonzáles C.A. Plackett-Burman design in the biosynthesis of silver nanoparticles with Mutisia acuminatta (Chinchircoma) and preliminary evaluation of its antibacterial activity. F1000 Res. 2023 12 1462 10.12688/f1000research.140883.1 38434649
    [Google Scholar]
  29. Yerlikaya F. Ozgen A. Vural I. Guven O. Karaagaoglu E. Khan M.A. Capan Y. Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach. J. Pharm. Sci. 2013 102 10 3748 3761 10.1002/jps.23686 23918313
    [Google Scholar]
  30. Canchi A. Khosa A. Singhvi G. Banerjee S. Dubey S.K. Design and characterization of polymeric nanoparticles of pioglitazone hydrochloride and study the effect of formulation variables using qbd approach. J. Drug Deliv. Ther. 2017 2 3 162 168
    [Google Scholar]
  31. Ekinci M. Yeğen G. Aksu B. İlem-Özdemir D. Preparation and evaluation of poly(lactic acid)/poly(vinyl alcohol) nanoparticles using the quality by design approach. ACS Omega 2022 7 38 33793 33807 10.1021/acsomega.2c02141 36188287
    [Google Scholar]
  32. Mirnezami S.M.S. Heydarinasab A. Akbarzadehkhyavi A. Adrjmand M. Development and optimization of lipid-polymer hybrid nanoparticles containing melphalan using central composite design and its effect on ovarian cancer cell lines. Iran. J. Pharm. Res. 2021 20 4 213 228 35194441
    [Google Scholar]
  33. Nikaeen G. Yousefinejad S. Rahmdel S. Samari F. Mahdavinia S. Central composite design for optimizing the biosynthesis of silver nanoparticles using plantago major extract and investigating antibacterial, antifungal and antioxidant activity. Sci. Rep. 2020 10 1 9642 10.1038/s41598‑020‑66357‑3 32541669
    [Google Scholar]
  34. Khan M.M. Zaidi S.S. Siyal F.J. Khan S.U. Ishrat G. Batool S. Mustapha O. Khan S. Din F. Statistical optimization of co-loaded rifampicin and pentamidine polymeric nanoparticles for the treatment of cutaneous leishmaniasis. J. Drug Deliv. Sci. Technol. 2023 79 104005 10.1016/j.jddst.2022.104005
    [Google Scholar]
  35. Murdande S.B. Shah D.A. Dave R.H. Impact of nanosizing on solubility and dissolution rate of poorly soluble pharmaceuticals. J. Pharm. Sci. 2015 104 6 2094 2102 10.1002/jps.24426 25821105
    [Google Scholar]
  36. Santos S. Neves A.R. Silva A. Barbosa M. Reis S. Barbosa J. Nanostructured lipid carriers loaded with resveratrol modulate human dendritic cells. Int. J. Nanomedicine 2016 11 3501 3516 10.2147/IJN.S108694 27555771
    [Google Scholar]
  37. Koshy O. Subramanian L. Thomas S. Differential scanning calorimetry in nanoscience and nanotechnology. Thermal and Rheological Measurement Techniques for Nanomaterials Characterization. Elsevier Amsterdam, Netherlands 2017 109 122 10.1016/B978‑0‑323‑46139‑9.00005‑0
    [Google Scholar]
  38. Weng J. Tong H.H.Y. Chow S.F. In vitro release study of the polymeric drug nanoparticles: Development and validation of a novel method. Pharmaceutics 2020 12 8 732 10.3390/pharmaceutics12080732 32759786
    [Google Scholar]
  39. Mead H. Paraskevopoulou V. Smith N. Gibson R. Amerio-Cox M. Taylor-Vine G. Armstrong T. Harris K. Wren S. Mann J. Developing a robust in vitro release method for a polymeric nanoparticle: Challenges and learnings. Int. J. Pharm. 2023 644 123317 10.1016/j.ijpharm.2023.123317 37586575
    [Google Scholar]
  40. Abbad S. Wang C. Waddad A.Y. Lv H. Zhou J. Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate. Int. J. Nanomedicine 2015 10 1 305 320 25609946
    [Google Scholar]
  41. Sun Y. Li B. Cao Q. Liu T. Li J. Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment. Stem Cell Res. Ther. 2022 13 1 489 10.1186/s13287‑022‑03180‑9 36182897
    [Google Scholar]
  42. Guinart A. Perry H.L. Wilton-Ely J.D.E.T. Tetley T.D. Gold nanomaterials in the management of lung cancer. Emerg. Top. Life Sci. 2020 4 6 627 643 10.1042/ETLS20200332 33270840
    [Google Scholar]
  43. Thakur R. Sharma A. Arora V. Nanoparticles methods for hydrophobic drugs — A novel approach: Graphical abstract. Materials Open 2023 1 2350002 10.1142/S2811086223500024
    [Google Scholar]
  44. Bhardwaj H. Jangde R.K. Current updated review on preparation of polymeric nanoparticles for drug delivery and biomedical applications. Next Nanotechnol. 2023 2 100013 10.1016/j.nxnano.2023.100013
    [Google Scholar]
  45. Iqbal M. Zafar N. Fessi H. Elaissari A. Double emulsion solvent evaporation techniques used for drug encapsulation. Int. J. Pharm. 2015 496 2 173 190 10.1016/j.ijpharm.2015.10.057 26522982
    [Google Scholar]
  46. Hoa L.T.M. Chi N.T. Nguyen L.H. Chien D.M. Preparation and characterisation of nanoparticles containing ketoprofen and acrylic polymers prepared by emulsion solvent evaporation method. J. Exp. Nanosci. 2012 7 2 189 197 10.1080/17458080.2010.515247
    [Google Scholar]
  47. Kızılbey K. Optimization of rutin-loaded plga nanoparticles synthesized by single-emulsion solvent evaporation method. ACS Omega 2019 4 1 555 562 10.1021/acsomega.8b02767
    [Google Scholar]
  48. Nordström P. Formation of polymeric nanoparticles encapsulating and releasing a new hydrophobic cancer drug. 2011
    [Google Scholar]
  49. Ullah F. Iqbal Z. Khan A. Khan S.A. Ahmad L. Alotaibi A. Ullah R. Shafique M. Formulation development and characterization of ph responsive polymeric nano-pharmaceuticals for targeted delivery of anti-cancer drug (methotrexate). Front. Pharmacol. 2022 13 911771 10.3389/fphar.2022.911771 35860013
    [Google Scholar]
  50. Wang J. Sui M. Fan W. Nanoparticles for tumor targeted therapies and their pharmacokinetics. Curr. Drug Metab. 2010 11 2 129 141 10.2174/138920010791110827 20359289
    [Google Scholar]
  51. Pandey A.P. Karande K.P. Sonawane R.O. Deshmukh P.K. Applying quality by design (QbD) concept for fabrication of chitosan coated nanoliposomes. J. Liposome Res. 2014 24 1 37 52 10.3109/08982104.2013.826243 23941613
    [Google Scholar]
  52. Liu D. Ge Y. Tang Y. Yuan Y. Zhang Q. Li R. Xu Q. Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation, characterization and in vitro studies. J. Microencapsul. 2010 27 8 726 734 10.3109/02652048.2010.513456 21034365
    [Google Scholar]
  53. Patra A. Satpathy S. Naik P.K. Kazi M. Hussain M.D. Folate receptor-targeted PLGA-PEG nanoparticles for enhancing the activity of genistein in ovarian cancer. Artif. Cells Nanomed. Biotechnol. 2022 50 1 228 239 10.1080/21691401.2022.2118758 36330543
    [Google Scholar]
  54. Dewangan H.K. Maurya L. Sharma R. Shah K. Soni S. Singh S. Optimization, evaluation and delivery of genistein loaded long circulating nanostructured lipid carriers for treatment of cancer melanoma cells. Res. Square 2023
    [Google Scholar]
  55. Badri W. Miladi K. Nazari Q.A. Fessi H. Elaissari A. Effect of process and formulation parameters on polycaprolactone nanoparticles prepared by solvent displacement. Colloids Surf. A Physicochem. Eng. Asp. 2017 516 238 244 10.1016/j.colsurfa.2016.12.029
    [Google Scholar]
  56. Chorny M. Fishbein I. Danenberg H.D. Golomb G. Study of the drug release mechanism from tyrphostin AG-1295-loaded nanospheres by in situ and external sink methods. J. Control. Release 2002 83 3 401 414 10.1016/S0168‑3659(02)00210‑9 12387948
    [Google Scholar]
  57. Santos D.T. Martín Á. Meireles M.A.A. Cocero M.J. Production of stabilized sub-micrometric particles of carotenoids using supercritical fluid extraction of emulsions. J. Supercrit. Fluids 2012 61 167 174 10.1016/j.supflu.2011.09.011
    [Google Scholar]
  58. Bao Y. Maeki M. Ishida A. Tani H. Tokeshi M. Effect of organic solvents on a production of plga-based drug-loaded nanoparticles using a microfluidic device. ACS Omega 2022 7 37 33079 33086 10.1021/acsomega.2c03137 36157756
    [Google Scholar]
  59. Javaid S. Ahmad N.M. Mahmood A. Nasir H. Iqbal M. Ahmad N. Irshad S. Cefotaxime loaded polycaprolactone based polymeric nanoparticles with antifouling properties for in-vitro drug release applications. Polymers (Basel) 2021 13 13 2180 10.3390/polym13132180 34209144
    [Google Scholar]
  60. Erfle P. Riewe J. Bunjes H. Dietzel A. Stabilized production of lipid nanoparticles of tunable size in taylor flow glass devices with high-surface-quality 3d microchannels. Micromachines (Basel) 2019 10 4 220 10.3390/mi10040220 30934803
    [Google Scholar]
  61. Ouchi H. Ishiguro H. Ikeda N. Hori M. Kubota Y. Uemura H. Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity. Int. J. Urol. 2005 12 1 73 80 10.1111/j.1442‑2042.2004.00973.x 15661057
    [Google Scholar]
  62. Tuli H.S. Tuorkey M.J. Thakral F. Sak K. Kumar M. Sharma A.K. Sharma U. Jain A. Aggarwal V. Bishayee A. Molecular mechanisms of action of genistein in cancer: Recent advances. Front. Pharmacol. 2019 10 1336 10.3389/fphar.2019.01336 31866857
    [Google Scholar]
  63. Jiang M. Gu D. Dai J. Huang Q. Tian L. Dark side of cytotoxic therapy: Chemoradiation-induced cell death and tumor repopulation. Trends Cancer 2020 6 5 419 431 10.1016/j.trecan.2020.01.018 32348737
    [Google Scholar]
/content/journals/raddf/10.2174/0126673878321778241010121358
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QbD-driven Formulation Development and Evaluation of Genistein Nanoparticles for Prostate Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0126673878321778241010121358
/content/journals/raddf/10.2174/0126673878321778241010121358
/content/journals/raddf/10.2174/0126673878321778241010121358
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  • Article Type:     Review Article
Keywords: cytotoxicity assessment ; polymeric nanoparticles ; Plackett–burman design (PBD) ; Genistein (GEN) ; Quality by design (QbD) ; prostate cancer ; Box–Behnken design (BBD)

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