Skip to content
2000
Volume 10, Issue 2
  • ISSN: 2405-4615
  • E-ISSN: 2405-4623

Abstract

Abemaciclib (Abm) is a CDK inhibitor that specifically targets the CDK4/6 cell cycle pathway and has potential anticancer activity. Unfortunately, it has a low solubility and dissolution rate.

Aim

The aim of this study is to enhance the solubility of Abm by loading it onto a chitosan (CS) polymer.

Methods

Polymer nanoparticle (NP) and Abm-CSNPs nanocomposites were prepared. Minitab 18 software was used to design 18 run samples to study the effects of CS, tripolyphosphate, and pH as independent variables on the loading efficiency and particle size (dependent variable). The response surface methodology (RSM) was also used to determine how the variables affected the response. The graphical analysis used surface plots, main effects plots, contour plots, and interaction graphs. The study includes F values, values, variance inflation factors (VIFs), adjusted sums of square (Adj SSs), adjusted mean squares (Adj MSs) and square error of the coefficient (SE Coef). The carriers and loaded samples were also examined using the results of tests, including Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. Furthermore, the release of Abm from Abm-CSNPs nanocomposite was studied .

Results

The results revealed an ability to produce particle sizes ranging from (168-192) nm and loading efficiencies from (56.7-62.1).

Conclusion

Abm-CSNPs nanocomposite may be used as an alternative drug delivery system for Abm to increase the release time of Abm to 1400 minutes.

Loading

Article metrics loading...

/content/journals/cnm/10.2174/0124054615288714240110072000
2024-02-13
2025-09-09
Loading full text...

Full text loading...

References

  1. BasatiG. Saffari-ChaleshtoriJ. AbbaszadehS. Asadi-SamaniM. Ashrafi-DehkordiK. Molecular dynamics mechanisms of the inhibitory effects of abemaciclib, hymenialdisine, and indirubin on CDK-6.Curr. Drug Res. Rev.201911213514110.2174/2589977511666191018180001 31875784
    [Google Scholar]
  2. SammonsS.L. ToppingD.L. BlackwellK.L.H.R. +, HER2-advanced breast cancer and CDK4/6 inhibitors: mode of action, clinical activity, and safety profiles.Curr. Cancer Drug Targets2017177637649 28359238
    [Google Scholar]
  3. Ates-AlagozZ. HassanM.A-K. Cyclin-dependent kinase 4/6 inhibitors against breast cancer.Mini Rev. Med. Chem.202323441242810.2174/1389557522666220606095540 35670349
    [Google Scholar]
  4. MartinJ.M. GoldsteinL.J. Profile of abemaciclib and its potential in the treatment of breast cancer.OncoTargets Ther.2018115253525910.2147/OTT.S149245 30214230
    [Google Scholar]
  5. KimE.S. Abemaciclib: First global approval.Drugs201777182063207010.1007/s40265‑017‑0840‑z 29128965
    [Google Scholar]
  6. AnsarinikZ. KiyaniH. YoosefianM. Investigation of self-assembled poly(ethylene glycol)-poly(L-lactic acid) micelle as potential drug delivery system for poorly water soluble anticancer drug abemaciclib.J. Mol. Liq.202236512019210.1016/j.molliq.2022.120192
    [Google Scholar]
  7. KakranM. LiL. MüllerR.H. Overcoming the challenge of poor drug solubility.Pharm Eng201232417
    [Google Scholar]
  8. ChowdaryK. Recent research on formulation development of BCS class II drugs–A review.Int. Res. J. Pharm. Appl. Sci.201331173181
    [Google Scholar]
  9. KawabataY. WadaK. NakataniM. YamadaS. OnoueS. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications.Int. J. Pharm.2011420111010.1016/j.ijpharm.2011.08.032 21884771
    [Google Scholar]
  10. BuniyaminI. AkhirR.M. AsliN.A. KhusaimiZ. MalekM.F. MahmoodM.R. Nanotechnology applications in biomedical systems.Curr. Nanomater.20227316718010.2174/2405461507666220301121135
    [Google Scholar]
  11. SarmahP. ChoudharyB. Nanomaterials for targeted delivery of anticancer drugs: An overview.Curr. Nanomater.202271313910.2174/2405461506666210119095130
    [Google Scholar]
  12. MehataA.K. DehariD. GuptaA. RabinD.C. MiyaA. Multifunctional liquid crystal nanoparticles for cancer therapy.Curr. Nanomater.20216141610.2174/2405461506666210118114851
    [Google Scholar]
  13. JhaS. MalviyaR. Role of nanostructured biomaterials in the treatment and diagnosis of biological disorder.Curr. Nanomater.202161233010.2174/2405461505999201027214348
    [Google Scholar]
  14. YusufA. AlmotairyA.R.Z. HenidiH. AlshehriO.Y. AldughaimM.S. Nanoparticles as drug delivery systems: A review of the implication of nanoparticles’ physicochemical properties on responses in biological systems.Polymers2023157159610.3390/polym15071596 37050210
    [Google Scholar]
  15. BegumM.Y. Advanced modeling based on machine learning for evaluation of drug nanoparticle preparation via green technology: Theoretical assessment of solubility variations.Case Stud. Therm. Eng.20234510302910.1016/j.csite.2023.103029
    [Google Scholar]
  16. WaisU. JacksonA.W. HeT. ZhangH. Nanoformulation and encapsulation approaches for poorly water-soluble drug nanoparticles.Nanoscale2016841746176910.1039/C5NR07161E 26731460
    [Google Scholar]
  17. GuoS. HuangL. Nanoparticles containing insoluble drug for cancer therapy.Biotechnol. Adv.201432477878810.1016/j.biotechadv.2013.10.002 24113214
    [Google Scholar]
  18. WeiW. LuM. XuW. PolyakovN.E. DushkinA.V. SuW. Preparation of protamine-hyaluronic acid coated core-shell nanoparticles for enhanced solubility, permeability, and oral bioavailability of decoquinate.Int. J. Biol. Macromol.202221834635510.1016/j.ijbiomac.2022.07.152 35878671
    [Google Scholar]
  19. KongY. WangW. WangC. LiL. PengD. TianB. Supersaturation and phase behavior during dissolution of amorphous solid dispersions.Int. J. Pharm.202363112252410.1016/j.ijpharm.2022.122524 36549404
    [Google Scholar]
  20. Correa SotoC.E. GaoY. IndulkarA.S. UedaK. ZhangG.G.Z. TaylorL.S. Impact of surfactants on the performance of clopidogrel-copovidone amorphous solid dispersions: Increased drug loading and stabilization of nanodroplets.Pharm. Res.202239116718810.1007/s11095‑021‑03159‑w 35013849
    [Google Scholar]
  21. YadavK. SachanA.K. KumarS. DubeyA. Techniques for increasing solubility: A review of conventional and new strategies.Asian J Pharm Res Dev202210214415310.22270/ajprd.v10i2.1054
    [Google Scholar]
  22. HuangH. ZhangY. LiuY. GuoY. HuC. Influence of intermolecular interactions on crystallite size in crystalline solid dispersions.Pharmaceutics20231510249310.3390/pharmaceutics15102493 37896253
    [Google Scholar]
  23. KhushbuJ.R. JindalR. Thermal stability and optimization of graphene oxide incorporated chitosan and sodium alginate based nanocomposite containing inclusion complexes of paracetamol and β-cyclodextrin for prolonged drug delivery systems.Polym. Bull.20238021751177210.1007/s00289‑022‑04157‑7
    [Google Scholar]
  24. kapoor D, Garg R, Gaur M, et al. Polymeric nanoparticles approach and identification and characterization of novel biomarkers for colon cancer. Results Chem2023610116710.1016/j.rechem.2023.101167
    [Google Scholar]
  25. ZouY. YueP. CaoH. Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion.Carbohydr. Polym.202330512054310.1016/j.carbpol.2023.120543 36737194
    [Google Scholar]
  26. MukherjeeC. VargheseD. KrishnaJ.S. Recent advances in biodegradable polymers – Properties, applications and future prospects.Eur. Polym. J.202319211206810.1016/j.eurpolymj.2023.112068
    [Google Scholar]
  27. PathakR. BhattS. PunethaV.D. PunethaM. Chitosan nanoparticles and based composites as a biocompatible vehicle for drug delivery: A review.Int. J. Biol. Macromol.2023253Pt 712736910.1016/j.ijbiomac.2023.127369 37839608
    [Google Scholar]
  28. HerdianaY. HusniP. NurhasanahS. ShamsuddinS. WathoniN. Chitosan-based nano systems for natural antioxidants in breast cancer therapy.Polymers20231513295310.3390/polym15132953 37447598
    [Google Scholar]
  29. MohiteP. RahayuP. MundeS. Chitosan-based hydrogel in the management of dermal infections: A review.Gels20239759410.3390/gels9070594 37504473
    [Google Scholar]
  30. KumarV. SharmaN. JanghuP. Synthesis and characterization of chitosan nanofibers for wound healing and drug delivery application.J. Drug Deliv. Sci. Technol.20238710485810.1016/j.jddst.2023.104858
    [Google Scholar]
  31. ZacaronT.M. SilvaM.L.S. CostaM.P. Advancements in chitosan-based nanoparticles for pulmonary drug delivery.Polymers20231518384910.3390/polym15183849 37765701
    [Google Scholar]
  32. HaseliS. PourmadadiM. SamadiA. A novel pH ‐responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan‐based nanocarrier: Emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction.Biotechnol. Prog.2022385e328010.1002/btpr.3280 35678755
    [Google Scholar]
  33. SoniS.S. D’EliaA.M. AlsasaA. Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype.Biomater. Sci.202210246951696710.1039/D2BM01113A 36341688
    [Google Scholar]
  34. HuangH. LouZ. ZhengS. Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage.Drug Deliv.202229176779110.1080/10717544.2022.2048130 35261301
    [Google Scholar]
  35. YuD.G. WangM. GeR. Strategies for sustained drug release from electrospun multi‐layer nanostructures.Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.2022143e177210.1002/wnan.1772 34964277
    [Google Scholar]
  36. AbadiA.J. MirzaeiS. MahabadyM.K. Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects.Phytother. Res.202236118921310.1002/ptr.7305 34697839
    [Google Scholar]
  37. HerdianaY. WathoniN. ShamsuddinS. MuchtaridiM. Drug release study of the chitosan-based nanoparticles.Heliyon202281e0867410.1016/j.heliyon.2021.e08674 35028457
    [Google Scholar]
  38. RosenD.B. KvarnhammarA.M. LauferB. TransCon IL-2 β/γ: A novel long-acting prodrug with sustained release of an IL-2Rβ/γ-selective IL-2 variant with improved pharmacokinetics and potent activation of cytotoxic immune cells for the treatment of cancer.J. Immunother. Cancer2022107e00499110.1136/jitc‑2022‑004991 35817480
    [Google Scholar]
  39. YuanH. ZhangZ. HuL. Development and characterization of gastro-floating sustained-release capsule with improved bioavailability of levodopa.Drug Deliv. Transl. Res.202313191710.1007/s13346‑022‑01188‑5 35661106
    [Google Scholar]
  40. GawadeA. PolshettiwarS. HingalajiaH. PrajapatiB.G. SinghA. Pharmacokinetics and pharmacodynamics of various novel formulations targeting Alzheimer’s disease. In: Alzheimer’s Disease and Advanced Drug Delivery Strategies.Elsevier2024391402
    [Google Scholar]
  41. KousarK. NaseerF. AbduhM.S. Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma.Front. Pharmacol.202313107300410.3389/fphar.2022.1073004 36712656
    [Google Scholar]
  42. SabziniM. PourmadadiM. YazdianF. Khadiv-ParsiP. RashediH. Development of chitosan/halloysite/graphitic carbon nitride nanovehicle for targeted delivery of quercetin to enhance its limitation in cancer therapy: An in vitro cytotoxicity against MCF-7 cells.Int. J. Biol. Macromol.202322615917110.1016/j.ijbiomac.2022.11.189 36435458
    [Google Scholar]
  43. KumarA. YadavS. PramanikJ. Chitosan-based composites: Development and perspective in food preservation and biomedical applications.Polymers20231515315010.3390/polym15153150 37571044
    [Google Scholar]
  44. Al-QubaisiM.S. Al-AbboodiA.S. AlhassanF.H. Preparation, characterization, in vitro drug release and anti-inflammatory of thymoquinone-loaded chitosan nanocomposite.Saudi Pharm. J.202230434735810.1016/j.jsps.2022.02.002 35527823
    [Google Scholar]
  45. Hussein-al-aliS.H. HusseinM.Z. AyoubR. FakuraziS. AbualassalQ.I.A. Al-DalahmehY. Development of new drug formulations: Cetirizine-polymers nanoparticles.Acta Pol. Pharm.2021783
    [Google Scholar]
  46. Abu ShararA.A. RamadanS.Z. Hussein-Al-AliS.H. Multiobjective optimization of fluphenazine nanocomposite formulation using NSGA-II method.Mater. Sci. Pol.202139451754410.2478/msp‑2021‑0042
    [Google Scholar]
  47. PrajapatiB.G. JivaniM. PaliwalH. Formulation and optimization of topical nanoemulsion based gel of mometasone furoate using 32 full factorial design.Indian Drugs20216061929
    [Google Scholar]
  48. ShahS. GhetiyaR. SoniwalaM. ChavdaJ. Development and optimization of inhalable levofloxacin nanoparticles for the treatment of tuberculosis.Curr. Drug Deliv.202118677979310.2174/1567201817999201103194626 33155907
    [Google Scholar]
  49. El BazA.F. ShetaiaY.M.H. ShamsE.H.A. ElMekawyA. Optimization of cellulase production by Trichoderma viride using response surface methodology.Curr. Biotechnol.201871192510.2174/2211550105666160115213402
    [Google Scholar]
  50. KumariM. GuptaS.K. Response surface methodological (RSM) approach for optimizing the removal of trihalomethanes (THMs) and its precursor’s by surfactant modified magnetic nanoadsorbents (sMNP) - An endeavor to diminish probable cancer risk.Sci. Rep.2019911833910.1038/s41598‑019‑54902‑8 31797998
    [Google Scholar]
  51. HuberL. Validation and qualification in analytical laboratories2007
    [Google Scholar]
  52. AllenT.T. AllenT.T. Software overview and methods review: Minitab: statistical quality control and design of experiments and systems. In: Introduction to Engineering Statistics and Lean Six Sigma. 2019575600
    [Google Scholar]
  53. LesikS.A. Applied statistical inference with MINITAB.CRC Press201810.1201/9780429444951
    [Google Scholar]
  54. Lewis-BeckM.S. SkalabanA. The R-squared: Some straight talk.Polit. Anal.1990215317110.1093/pan/2.1.153
    [Google Scholar]
  55. BoylanG.L. ChoB.R. The normal probability plot as a tool for understanding data: A shape analysis from the perspective of skewness, kurtosis, and variability.Qual. Reliab. Eng. Int.201228324926410.1002/qre.1241
    [Google Scholar]
  56. Abul KalamM. KhanA.A. KhanS. AlmalikA. AlshamsanA. Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box–Behnken experimental design.Int. J. Biol. Macromol.20168732934010.1016/j.ijbiomac.2016.02.033 26893052
    [Google Scholar]
  57. LarsenW.A. McClearyS.J. The use of partial residual plots in regression analysis.Technometrics197214378179010.1080/00401706.1972.10488966
    [Google Scholar]
  58. TranmerM. ElliotM. Multiple linear regression.CMI20085515
    [Google Scholar]
  59. PokkallaD.K. WangZ. TeohJ.C. PohL.H. LimC.T. QuekS.T. Soft missing rib structures with controllable negative poisson’s ratios over large strains via isogeometric design optimization.J. Eng. Mech.2022148110402206310.1061/(ASCE)EM.1943‑7889.0002149
    [Google Scholar]
  60. LeeR. Statistical design of experiments for screening and optimization.Chemieingenieurtechnik 201991319120010.1002/cite.201800100
    [Google Scholar]
  61. MuleyA.B. LadoleM.R. SuprasannaP. DalviS.G. Intensification in biological properties of chitosan after γ-irradiation.Int. J. Biol. Macromol.201913143544410.1016/j.ijbiomac.2019.03.072 30876903
    [Google Scholar]
  62. AnandM. SathyapriyaP. MaruthupandyM. Hameedha BeeviA. Synthesis of chitosan nanoparticles by TPP and their potential mosquito larvicidal application.Front Laborat Med201822727810.1016/j.flm.2018.07.003
    [Google Scholar]
  63. JiaZ. YangC. ZhaoF. ChaoX. LiY. XingH. One-step reinforcement and deacidification of paper documents: Application of Lewis base—Chitosan nanoparticle coatings and analytical characterization.Coatings20201012122610.3390/coatings10121226
    [Google Scholar]
  64. AnwerM.K. FatimaF. AhmedM.M. Abemaciclib-loaded ethylcellulose based nanosponges for sustained cytotoxicity against MCF-7 and MDA-MB-231 human breast cancer cells lines.Saudi Pharm. J.202230672673410.1016/j.jsps.2022.03.019 35812154
    [Google Scholar]
  65. LeiZ. AlwanM. AlamirH.T.A. Detection of abemaciclib, an anti-breast cancer agent, using a new electrochemical DNA biosensor.Front Chem.20221098016210.3389/fchem.2022.980162 36339035
    [Google Scholar]
  66. KhorsandiZ. HajipourA.R. SarfjooM.R. VarmaR.S. A Pd/Cu-Free magnetic cobalt catalyst for C–N cross coupling reactions: Synthesis of abemaciclib and fedratinib.Green Chem.202123145222522910.1039/D1GC00518A
    [Google Scholar]
  67. LustrianeC. DwivanyF.M. SuendoV. RezaM. Effect of chitosan and chitosan-nanoparticles on post harvest quality of banana fruits.J. Plant Biotechnol.2018451364410.5010/JPB.2018.45.1.036
    [Google Scholar]
  68. BhumkarD.R. PokharkarV.B. Studies on effect of pH on cross-linking of chitosan with sodium tripolyphosphate: A technical note.AAPS PharmSciTech200672E138E14310.1208/pt070250 16796367
    [Google Scholar]
  69. KarimiM. AvciP. AhiM. GazoriT. HamblinM.R. Naderi-ManeshH. Evaluation of chitosan-tripolyphosphate nanoparticles as a p-shRNA delivery vector: formulation, optimization and cellular uptake study.J. Nanopharm. Drug Deliv.20131326627810.1166/jnd.2013.1027 26989641
    [Google Scholar]
/content/journals/cnm/10.2174/0124054615288714240110072000
Loading
/content/journals/cnm/10.2174/0124054615288714240110072000
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): Abemaciclib; breast cancer treatment; chitosan; nanocomposites; optimization; release study
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test