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Volume 17, Issue 1
  • ISSN: 1876-4029
  • E-ISSN: 1876-4037

Abstract

Introduction

Prostate cancer is the second most often occurring cancer in males and the fourth most common cancer overall. Beta-sitosterol (β-Sit), the most prevalent plant phytosterol found in several plant species, has been reported to have inhibitory effects against several malignancies. Even though β-Sit has considerable potential, its therapeutic uses are limited due to its poor aqueous solubility (<0.1 mg/ml), low bioavailability (0.41%), and poor absorption from GIT. Nanosuspension is one of the most innovative approaches to address problems linked to low solubility and poor absorption.

Methods

In the present research work, β-Sit nanosuspension has been fabricated by nanoprecipitation-ultrasonication, followed by high-pressure homogenization (Panda plus 2000) employing HPMC E5 and poloxamer (188 and 407) as stabilizers, optimized using a Box-Behnken technique. Subsequently, nano gel was prepared by dispersion method using gellan gum as an ion-sensitive polymer by incorporating optimized nanosuspension.

Results

The optimized nanosuspension was evaluated for various parameters and has been found to have an average particle size (137 ± 5.07 nm), zeta potential (-24 ± 4.99), PDI (0.207), and improved solubility up to 5 folds, being suitable for systemic absorption through the nasal route. The optimized gel was characterized and showed the desired viscosity, good spreadability, acceptable gelation property, and sufficient mucoadhesive strength to adhere to nasal mucosa after ionic interaction. The release of pure drug, nanosuspension, and the optimized gel was compared, and optimized gel showed a maximum release of 91.41 ± 1.32% up to 8 hours.

Conclusion

It was concluded that the nasal nanogel could be the best possible approach to delivering β-Sit into systemic circulation for the treatment of prostate cancer.

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References

  1. SekhoachaM. RietK. MotloungP. GumenkuL. AdegokeA. MasheleS. Prostate cancer review: Genetics, diagnosis, treatment options, and alternative approaches.Molecules20222717573010.3390/molecules27175730 36080493
     [Google Scholar]
  2. WangL. LuB. HeM. WangY. WangZ. DuL. Prostate cancer incidence and mortality: Global status and temporal trends in 89 countries from 2000 to 2019.Front. Public Health20221081104410.3389/fpubh.2022.811044 35252092
     [Google Scholar]
  3. BarsoukA. PadalaS.A. VakitiA. MohammedA. SaginalaK. ThandraK.C. RawlaP. BarsoukA. Epidemiology, staging and management of prostate cancer.Med. Sci. (Basel)2020832810.3390/medsci8030028 32698438
     [Google Scholar]
  4. AndimaM. CostabileG. IsertL. NdakalaA.J. DereseS. MerkelO.M. Evaluation of β-Sitosterol loaded PLGA and PEG-PLA nanoparticles for effective treatment of breast cancer: Preparation, physicochemical characterization, and antitumor activity.Pharmaceutics201810423210.3390/pharmaceutics10040232 30445705
     [Google Scholar]
  5. KhanZ. NathN. RaufA. EmranT.B. MitraS. IslamF. ChandranD. BaruaJ. KhandakerM.U. IdrisA.M. WilairatanaP. ThiruvengadamM. Multifunctional roles and pharmacological potential of β-sitosterol: Emerging evidence toward clinical applications.Chem. Biol. Interact.202236511011710.1016/j.cbi.2022.110117 35995256
     [Google Scholar]
  6. von HoltzRL. FinkCS. AwadAB. beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells.Nutr Cancer.199832183210.1080/01635589809514709
     [Google Scholar]
  7. BaskarA.A. IgnacimuthuS. PaulrajG.M. Al NumairK.S. Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an in vitro and in vivo study.BMC Complement. Altern. Med.20101012410.1186/1472‑6882‑10‑24 20525330
     [Google Scholar]
  8. AwadA.B. DownieA.C. FinkC.S. Inhibition of growth and stimulation of apoptosis by beta-sitosterol treatment of MDA-MB-231 human breast cancer cells in culture.Int. J. Mol. Med.20005554154510.3892/ijmm.5.5.541 10762659
     [Google Scholar]
  9. ParkC. MoonD.O. RhuC.H. ChoiB.T. LeeW.H. KimG.Y. ChoiY.H. β-sitosterol induces anti-proliferation and apoptosis in human leukemic U937 cells through activation of caspase-3 and induction of Bax/Bcl-2 ratio.Biol. Pharm. Bull.20073071317132310.1248/bpb.30.1317 17603173
     [Google Scholar]
  10. DesaiK. McManusJ.M. SharifiN. Hormonal therapy for prostate cancer.Endocr. Rev.202142335437310.1210/endrev/bnab002 33480983
     [Google Scholar]
  11. GjyreziA. XieF. VoznesenskyO. KhannaP. CalaguaC. BaiY. KungJ. WuJ. CoreyE. MontgomeryB. MaceS. GianolioD.A. BubleyG.J. BalkS.P. GiannakakouP. BhattR.S. Taxane resistance in prostate cancer is mediated by decreased drug-target engagement.J. Clin. Invest.202013063287329810.1172/JCI132184 32478682
     [Google Scholar]
  12. YunhongM. MingM. YenheS. Abelmoschus manihot flower containing traditional Chinese medicine preparation for preventing and treating prostate disease and preparation method of traditional Chinese medicine preparation.CN105434684A2016
  13. AwadA. RoyR. FinkC. β-sitosterol, a plant sterol, induces apoptosis and activates key caspases in MDA-MB-231 human breast cancer cells.Oncol. Rep.200310249750010.3892/or.10.2.497 12579296
     [Google Scholar]
  14. a AfzalO. AkhterM.H. AhmadI. MuzammilK. DawriaA. ZeyaullahM. AltamimiA.S. KhalilullahH. Mir Najib UllahS.N. RahmanM.A. AliA. A β-sitosterol encapsulated biocompatible alginate/chitosan polymer nanocomposite for the treatment of breast cancer.Pharmaceutics2022148171110.3390/pharmaceutics14081711. 36015337
     [Google Scholar]
  15. (b RajR.K. EzhilarasanD. RajeshkumarS. β-Sitosterol-assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via oxidative stress in human hepatocellular cancer cell line.J. Biomed. Mater. Res. A2020108918991908 32319188
     [Google Scholar]
  16. AbdouE.M. FayedM.A.A. HelalD. AhmedK.A. Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted β-Sitosterol against CCl4 induced hepatotoxicity in rats.Sci. Rep.2019911977910.1038/s41598‑019‑56320‑2 31875004
     [Google Scholar]
  17. MedjmedjA. Ngalle-LothA. ClemençonR. HamacekJ. PichonC. PercheF. In cellulo and in vivo comparison of cholesterol, beta-sitosterol and dioleylphosphatidylethanolamine for lipid nanoparticle formulation of mRNA.Nanomaterials (Basel)20221214244610.3390/nano12142446 35889670
     [Google Scholar]
  18. AbeeshP. GuruvayoorappanC. Preparation and characterization of beta sitosterol encapsulated nanoliposomal formulation for improved delivery to cancer cells and evaluation of its anti-tumor activities against Daltons Lymphoma Ascites tumor models.J. Drug Deliv. Sci. Technol.20227010283210.1016/j.jddst.2021.102832
     [Google Scholar]
  19. LakshmiP. KumarG.A. Nanosuspension technology: A review.Int. J. Pharma Sci.2010243540[Available from: https://www.researchgate.net/publication/285869829_Nanosuspens ion_technology_A_review
    [Google Scholar]
  20. AgrawalY.K. PatelV.R. Nanosuspension: An approach to enhance solubility of drugs.J. Adv. Pharm. Technol. Res.201122818710.4103/2231‑4040.82950 22171298
     [Google Scholar]
  21. ChandraA. SharmaU. JainS.K. SoniR.K. Nanosuspension: An overview.J. Drug Deliv. Ther.20133616216710.22270/jddt.v3i6.677
     [Google Scholar]
  22. LiX. YuanH. ZhangC. ChenW. ChengW. ChenX. YeX. Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement.J. Pharm. Pharmacol.201668898098810.1111/jphp.12575 27283220
     [Google Scholar]
  23. PatelH.M. PatelU.B. ShahC. AkbariB. Formulation and development of nanosuspension as an alternative approach for solubility and dissolution enhancement of aceclofenac.Int. J. Adv. Pharm.2018753347[Available from: https://core.ac.uk/download/pdf/335078055.pdf
    [Google Scholar]
  24. AhireE. ThakkarS. DarshanwadM. MisraM. Parenteral nanosuspensions: A brief review from solubility enhancement to more novel and specific applications.Acta Pharm. Sin. B20188573375510.1016/j.apsb.2018.07.011 30245962
     [Google Scholar]
  25. GeethaG. PoojithaU. KhanK.A. Various techniques for preparation of nanosuspension-a review.Int. J. Pharma Res. Rev.2014393037[Available from: https://www.researchgate.net/publication/290485127_Various_tech niques_for_preparation_of_nanosuspension_-_a_review
    [Google Scholar]
  26. PawarS.S. DahifaleB.R. NagargojeS.P. ShendgeR.S. Nanosuspension technologies for delivery of drugs.Nanosci Nanotech Res.201742596610.12691/nnr‑4‑2‑4
     [Google Scholar]
  27. GaoL. LiuG. WangX. LiuF. XuY. MaJ. Preparation of a chemically stable quercetin formulation using nanosuspension technology.Int. J. Pharm.20114041-223123710.1016/j.ijpharm.2010.11.009 21093559
     [Google Scholar]
  28. KukD.H. HaE.S. HaD.H. SimW.Y. LeeS.K. JeongJ.S. KimJ.S. BaekI. ParkH. ChoiD.H. YooJ.W. JeongS.H. HwangS.J. KimM.S. Development of a resveratrol nanosuspension using the antisolvent precipitation method without solvent removal, based on a quality by design (QbD) approach.Pharmaceutics2019111268810.3390/pharmaceutics11120688 31861173
     [Google Scholar]
  29. CharyS.S. BhikshapathiD.V.R.N. VamsiN.M. KumarJ.P. Optimizing entrectinib nanosuspension: Quality by design for enhanced oral bioavailability and minimized fast-fed variability.Bionanoscience20241910.1007/s12668‑024‑01462‑5
     [Google Scholar]
  30. AlsaidanO.A. PattanayakP. AwasthiA. AlruwailiN.K. ZafarA. AlmawashS. GulatiM. SinghS.K. Quality by design-based optimization of formulation parameters to develop quercetin nanosuspension for improving its biopharmaceutical properties.S. Afr. J. Bot.202214979880610.1016/j.sajb.2022.04.030
     [Google Scholar]
  31. AlsabeelahN. KumarV. Quality by design‐based optimization of formulation and process parameters for berberine nanosuspension for enhancing its dissolution rate, bioavailability, and cardioprotective activity.J. Food Biochem.20224610e1436110.1111/jfbc.14361 35929374
     [Google Scholar]
  32. BitterlichA. MihorkoA. JuhnkeM. Design space and control strategy for the manufacturing of wet media milled drug nanocrystal suspensions by adopting mechanistic process modeling.Pharmaceutics202416332810.3390/pharmaceutics16030328 38543222
     [Google Scholar]
  33. RoldanT.L. LiS. GuillonC. HeindelN.D. LaskinJ.D. LeeI.H. GaoD. SinkoP.J. Optimizing nanosuspension drug release and wound healing using a design of experiments approach: Improving the drug delivery potential of NDH-4338 for treating chemical burns.Pharmaceutics202416447110.3390/pharmaceutics16040471 38675132
     [Google Scholar]
  34. AlagusundaramM. ChengaiahB. GnanaprakashK. RamkanthS. ChettyC.M. DhachinamoorthiD. Nasal drug delivery system-An overview.Int. J. Res. Pharm. Sci.201014454465[Available from https://www.researchgate.net/publication/49601002_Nasal_drug_d elivery_system_-_an_overview
    [Google Scholar]
  35. KatareP. Pawar MedheT. NadkarniA. DeshpandeM. TekadeR.K. BenivalD. JainA. Nasal drug delivery system and devices: An overview on health effects. J. ACS.Chem. Health Saf.202431212714310.1021/acs.chas.3c00069
     [Google Scholar]
  36. LaffleurF. BauerB. Progress in nasal drug delivery systems.Int. J. Pharm.202160712099410.1016/j.ijpharm.2021.120994 34390810
     [Google Scholar]
  37. ScherließR. Nasal formulations for drug administration and characterization of nasal preparations in drug delivery.Ther. Deliv.202011318319110.4155/tde‑2019‑0086 32046624
     [Google Scholar]
  38. EhrickJ.D. ShahS.A. ShawC. KulkarniV.S. CoowanitwongI. DeS. SumanJ.D. Considerations for the development of nasal dosage forms.Sterile Product Development201369914410.1007/978‑1‑4614‑7978‑9_5
     [Google Scholar]
  39. HarrisE. FDA will evaluate first self-administered FluMist vaccine.JAMA202333020194510.1001/jama.2023.21870 37938864
     [Google Scholar]
  40. KanebA. BerardinoK. HanukaaiJ.S. RooneyK. KayeA.D. Calcitonin (FORTICAL, MIACALCIN) for the treatment of vertebral compression fractures.Orthop. Rev. (Pavia)20211322497610.52965/001c.24976 34745472
     [Google Scholar]
  41. UmarM. MalikM.O. IqbalS. QurbanA. SadiqA. ZanibSS. TararM.T. An analysis of bibliometric research on sumatriptan (Imitrex, Tosymra) linked to migraine relief: Sumatriptan and migraine relief.Futur. Biotech2023596510.54393/fbt.v3i03.70
     [Google Scholar]
  42. MartinV. HoekmanJ. AuroraS.K. ShrewsburyS.B. Nasal delivery of acute medications for migraine: The upper versus lower nasal space.J. Clin. Med.20211011246810.3390/jcm10112468 34199479
     [Google Scholar]
  43. SchoenenJ. SawyerJ. Zolmitriptan (Zomig™, 311C90), a novel dual central and peripheral 5HT1B/1D agonist: An overview of efficacy.Cephalalgia19971718Suppl.284010.1177/0333102497017S1805 9399015
     [Google Scholar]
  44. PfaffenrathV. FenzlE. BregmanD. FärkkilaM. Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial.Cephalalgia2012321076677710.1177/0333102412451359 22711895
     [Google Scholar]
  45. KongsgaardU.E. EegM. GreisenH. The use of Instanyl® in the treatment of breakthrough pain in cancer patients: A 3-month observational, prospective, cohort study.Support. Care Cancer20142261655166210.1007/s00520‑014‑2128‑0 24510192
     [Google Scholar]
  46. ChaniotiS. KatsouliM. TziaC. β-Sitosterol as a functional bioactive.A Centum of Valuable Plant Bioactives202119321210.1016/B978‑0‑12‑822923‑1.00014‑5
     [Google Scholar]
  47. WangT. MaC. HuY. GuoS. BaiG. YangG. YangR. Effects of food formulation on bioavailability of phytosterols: Phytosterol structures, delivery carriers, and food matrices.Food Funct.202314125465547710.1039/D3FO00566F 37232095
     [Google Scholar]
  48. LorenzeA. HsuehW. NasrJ. Beta-sitosterol-induced acute pancreatitis: A case report and review of the literature.Cureus2020123e740710.7759/cureus.7407 32226701
     [Google Scholar]
  49. AhmadS.R. GhoshP. A systematic investigation on flavonoids, catechin, β-sitosterol and lignin glycosides from Saraca asoca (ashoka) having anti-cancer & antioxidant properties with no side effect.J. Indian Chem. Soc.202299110029310.1016/j.jics.2021.100293
     [Google Scholar]
  50. GuptaE. β-Sitosterol: Predominant phytosterol of therapeutic potential. Innovations in Food TechnologySpringer202046547710.1007/978‑981‑15‑6121‑4_32
     [Google Scholar]
  51. UsmanM.R. Salgar SurekhaU. Salkar RashmiJ. LalitS. High performance thin layer chromatographic method for quantification of β-sitosterol from Vanda roxburghii R.Br. Asian J. Plant Sci. Res.20122524529[Available from: https://www.imedpub.com/articles-pdfs/high-performance-thin-layerchromatographic-method-for-quantification-of-sitosterol-fromvanda- roxburghii-rbr.pdf
    [Google Scholar]
  52. BulamaJ.S. DangoggoS.M. MathiasS.N. Isolation and characterization of beta-sitosterol from ethyl acetate extract of root bark of Terminalia glaucescens.IJSRP Journal20155313[Available from https://www.academia.edu/11740080/Isolation_and_Characterization_of_Beta_Sitosterol_from_ethyl_acetate_extract_of_root_bark_of_Terminalia_glaucescens
    [Google Scholar]
  53. AhmadH. SehgalS. MishraA. GuptaR. SarafS.A. TLC detection of β-sitosterol in Michelia champaca L. leaves and stem bark and it’s determination by HPTLC.Pharmacogn. J.2012427455510.5530/pj.2012.27.8
     [Google Scholar]
  54. AmkarA.J. RaneB.R. JainA.S. Development and evaluation of nanosuspension loaded nanogel of nortriptyline HCl for brain delivery.Eng. Proc.20235615810.3390/ASEC2023‑15311
     [Google Scholar]
  55. A.Zeez R.; S Abaas, I.; J Kadhim, E. Isolation and characterization of β-sitosterol from Elaeagnus angustifolia cultivated in Iraq.Asian J. Pharm. Clin. Res.2018111144244610.22159/ajpcr.2018.v11i11.29030
     [Google Scholar]
  56. ShindeM.E. MaruA.D. SonawaneM.P. VadjeS.S. PatilK.R. Nanosuspension: An promising approach to enhance solubility of poorly soluble drugs.World J. Pharm. Res.2020910
     [Google Scholar]
  57. JacobS. NairA.B. ShahJ. Emerging role of nanosuspensions in drug delivery systems.Biomater. Res.2020241310.1186/s40824‑020‑0184‑8 31969986
     [Google Scholar]
  58. GuanW. MaY. DingS. LiuY. SongZ. LiuX. TangL. WangY. The technology for improving stability of nanosuspensions in drug delivery.J. Nanopart. Res.20222411410.1007/s11051‑022‑05403‑9
     [Google Scholar]
  59. MdS. AlhakamyN.A. AkhterS. AwanZ.A.Y. AldawsariH.M. AlharbiW.S. HaqueA. ChoudhuryH. SivakumarP.M. Development of polymer and surfactant based naringenin nanosuspension for improvement of stability, antioxidant, and antitumour activity.J. Chem.2020202011010.1155/2020/3489393
     [Google Scholar]
  60. CortésH. Hernández-ParraH. Bernal-ChávezS.A. Prado-AudeloM.L.D. Caballero-FloránI.H. Borbolla-JiménezF.V. González-TorresM. MagañaJ.J. Leyva-GómezG. Non-ionic surfactants for stabilization of polymeric nanoparticles for biomedical uses.Materials (Basel)20211412319710.3390/ma14123197 34200640
     [Google Scholar]
  61. OktayA.N. Ilbasmis-TamerS. KarakucukA. CelebiN. Screening of stabilizing agents to optimize flurbiprofen nanosuspensions using experimental design.J. Drug Deliv. Sci. Technol.20205710169010.1016/j.jddst.2020.101690
     [Google Scholar]
  62. WeiD. WangL. LiuC. WangB. β-Sitosterol solubility in selected organic solvents.J. Chem. Eng. Data20105582917291910.1021/je9009909
     [Google Scholar]
  63. ShidL.R. DholeS.N. KulkarniN. ShidL. S.L. Formulation and evaluation of nanosuspension delivery system for simvastatin.Int. J. Pharm. Sci. Nanotechnol.2014722459247510.37285/ijpsn.2014.7.2.8
     [Google Scholar]
  64. LiuH. GalbraithS.C. RicartB. StantonC. Smith-GoettlerB. VerdiL. O’ConnorT. LeeS. YoonS. Optimization of critical quality attributes in continuous twin-screw wet granulation via design space validated with pilot scale experimental data.Int. J. Pharm.2017525124926310.1016/j.ijpharm.2017.04.055 28450171
     [Google Scholar]
  65. RameshY. SarayuB. Hari ChandanaG. NeelimaO. SanaS. Formulation and evaluation of lamivudine nanosuspension.J. Drug Deliv. Ther.2021114-S717710.22270/jddt.v11i4‑S.4961
     [Google Scholar]
  66. ButaniS. Fabrication of an ion-sensitive in situ gel loaded with nanostructured lipid carrier for nose to brain delivery of donepezil.Asian J. Pharm.2018124293302[Available from: https://www.researchgate.net/publication/332138952_Fabrication_ of_an_ion-sensitive_in_situ_gel_loaded_with_nanostructured_ lipid_ carrier_for_nose_to_brain_delivery_of_Donepezil
    [Google Scholar]
  67. GalgatteU.C. KumbharA.B. ChaudhariP.D. Development of in situ gel for nasal delivery: Design, optimization, in vitro and in vivo evaluation.Drug Deliv.2014211627310.3109/10717544.2013.849778 24191774
     [Google Scholar]
  68. UttarwarS. Formulation and development of in situ gelling system for nasal administration for an antiemetic drug ondansetron hydrochloride by using Pluronics 127P and Pluronics 68.Int. J. Res. Pharm. Biomed. Sci.2012311031108[Available from: https://www.semanticscholar.org/paper/Formulation-and- Development-of-In-Situ-Gelling-for- Uttarwar/87966384e3e1dc9b2ece4babdda2195fa3bd7c57
    [Google Scholar]
  69. NairA.B. ChaudharyS. JacobS. PatelD. ShinuP. ShahH. ChaudharyA. AldhubiabB. AlmuqbilR.M. AlnaimA.S. AlqattanF. ShahJ. Intranasal administration of dolutegravir-loaded nanoemulsion-based in situ gel for enhanced bioavailability and direct brain targeting.Gels20239213010.3390/gels9020130 36826300
     [Google Scholar]
  70. PatelA.U. ShahP.P. ShahP. ShahS. Formulation development and evaluation of thermoreversible mucoadhesive in situ nasal gel of asenapine maleate.Curr. Psychopharmacol.201549991110.2174/2211556004666150525224515
     [Google Scholar]
  71. SherafudeenS.P. VasanthaP.V. Development and evaluation of in situ nasal gel formulations of loratadine.Res. Pharm. Sci.2015106466476 26779266
     [Google Scholar]
  72. BorasteS.V. PatilS.B. Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride.Drug Dev. Ind. Pharm.2024501112210.1080/03639045.2023.2291463 38054848
     [Google Scholar]
  73. DingX. GuoL. DuQ. WangT. ZengZ. WangY. CuiH. GaoF. CuiB. Preparation and comprehensive evaluation of the efficacy and safety of chlorantraniliprole nanosuspension.Toxics20241217810.3390/toxics12010078 38251033
     [Google Scholar]
/content/journals/mns/10.2174/0118764029328588240816075844
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Preparation and Optimization of Beta-Sitosterol Nanosuspension-Loaded In situ Gel by Using Box-Behnken Model for the Treatment of Prostate Cancer
Micro and Nanosystems 17, 27 (2025); https://doi.org/10.2174/0118764029328588240816075844
/content/journals/mns/10.2174/0118764029328588240816075844
/content/journals/mns/10.2174/0118764029328588240816075844
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  • Article Type:     Research Article
Keyword(s): Beta-sitosterol; Box-Behnken model; high-pressure homogenization; in situ nanogel; nanosuspension; nanotechnology; optimization; prostate cancer

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