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2000
Volume 22, Issue 10
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Background

Gemcitabine (Gem) is a well-known antineoplastic drug used to treat several solid tumors. The clinical application of Gem is hampered owing to its non-selectivity, short half-life, and drug resistance, which, therefore, necessitate the development of a suitable novel formulation that can selectively target cancer sites.

Methods

In present work, Gem-loaded bovine serum albumin nanoparticles (Gem-BSANPs) have been prepared by using the desolvation cross-linking method and coated with hyaluronic acid (HA-Gem-BSANPs) to target the CD44 receptor which overexpressed on several solid tumors. The developed NPs were characterized by particle size, zeta potential, Transmission Electron Microscopy (TEM), and Differential Scanning Calorimetry (DSC). Further anticancer activity of the developed formulation was evaluated against A549 and MCF-7 cells and explored mode of action studies.

Results

The mean particle size and zeta potential of HA-Gem-BSANPs were observed as 144.7±5.67 nm and -45.72±3.24 mV, respectively. The TEM analysis also corroborated the particle size and shape, while thermal analysis (DSC) indicated that Gem was entrapped into NPs in an amorphous form. The nucleoside transport inhibition assay demonstrated that the NPs do not depend on transporters for cellular internalization, and hence, resistance development in cells is less expected against this formulation. HA-Gem-BSANPs exhibited higher cytotoxicity and apoptosis on both the tested cell lines. However, better cell-killing ability and mitochondrial membrane potential loss were observed against A549 due to CD44 expression.

Conclusion

The present work demonstrated that HA-Gem-BSANPs could be a potential strategy to improve Gem's therapeutic efficacy by selectively targeting the tumor site.

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2025-02-12
2025-12-15

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References

  1. LiuC. G. HanY. H. KankalaR. K. WangS. Bin; Chen, A. Z. Subcellular Performance of Nanoparticles in Cancer Therapy.Int. J. Nanomedicine20201567570410.2147/IJN.S226186
     [Google Scholar]
  2. CarmichaelJ. FinkU. RussellR. C. G. SpittleM. F. HarrisA. L. SpiessiG. BlatterJ. Phase II Study of Gemcitabine in Patients with Advanced Pancreatic Cancer.Br. J. Cancer199673110110510.1038/bjc.1996.18
     [Google Scholar]
  3. YardleyD. A. Gemcitabine plus Paclitaxel in Breast Cancer.Semin. Oncol.200532SUPPL. 6142110.1053/j.seminoncol.2005.06.025
     [Google Scholar]
  4. OzolsR. F. Gemcitabine and Carboplatin in Second-Line Ovarian Cancer.Semin. Oncol.200532SUPPL. 6410.1053/j.seminoncol.2005.06.023
     [Google Scholar]
  5. HoangT. KimK. M. JaslowskiA. KochP. BeattyP. McGovernJ. QuisumbingM. ShapiroG. WitteR. SchillerJ. H. Phase II Study of Second-Line Gemcitabine in Sensitive or Refractory Small Cell Lung Cancer.Lung Cancer20034219710210.1016/S0169‑5002(03)00273‑3
     [Google Scholar]
  6. HeinemannV. XuY.Z. ChubbS. SenA. PlunkettW. HertelL.W. GrindeyG.B. HeinemannV. Cellular Elimination of 2′,2′-Difluorodeoxycytidine 5′-Triphosphate: A Mechanism of Self-Potentiation.Cancer Res.1992523533539
     [Google Scholar]
  7. NeffT. BlauC.A. Forced Expression of Cytidine Deaminase Confers Resistance to Cytosine Arabinoside and Gemcitabine.Exp. Hematol.1996241113401346
     [Google Scholar]
  8. MackeyJ.R. ManiR.S. SelnerM. MowlesD. YoungJ.D. BeltJ.A. CrawfordC.R. CassC.E. Functional Nucleoside Transporters Are Required for Gemcitabine Influx and Manifestation of Toxicity in Cancer Cell Lines.Cancer Res.1998581943494357
     [Google Scholar]
  9. DubeyR.D. AlamN. SanejaA. KhareV. KumarA. VaidhS. MahajanG. SharmaP.R. SinghS.K. MondheD.M. GuptaP.N. Development and Evaluation of Folate Functionalized Albumin Nanoparticles for Targeted Delivery of Gemcitabine.Elsevier B.V.2015Vol. 49210.1016/j.ijpharm.2015.07.012
     [Google Scholar]
  10. MieleE. SpinelliG. P. MieleE. TomaoF. TomaoS. Albumin-Bound Formulation of Paclitaxel (Abraxane® ABI-007) in the Treatment of Breast Cancer.Int. J. Nanomedicine2009419910510.2147/ijn.s3061
     [Google Scholar]
  11. GreenM. R. ManikhasG. M. OrlovS. AfanasyevB. MakhsonA. M. BharP. HawkinsM. J. Abraxane®, a Novel Cremophor®-Free, Albumin-Bound Particle Form of Paclitaxel for the Treatment of Advanced Non-Small-Cell Lung Cancer.Ann. Oncol.20061781263126810.1093/annonc/mdl104
     [Google Scholar]
  12. DosioF. ArpiccoS. StellaB. FattalE. Hyaluronic Acid for Anticancer Drug and Nucleic Acid Delivery.Adv. Drug Deliv. Rev.20159720423610.1016/j.addr.2015.11.011
     [Google Scholar]
  13. BregadzeV. I. SivaevI. B. SemioshkinA. Shmal’koA. V. KosenkoI. D. LebedevaK. V. MandalS. SreejyothiP. DubeyR. D. SarkarA. ShenZ. WuA. HosmaneN. S. Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides.Chem. A Eur. J.202026138321384110.1002/chem.201905083
     [Google Scholar]
  14. DubeyR. D. SarkarA. ShenZ. BregadzeV. I. SivaevI. B. DruzinaA. A. ZhidkovaO. B. Shmal’koA. V. KosenkoI. D. PS. MandalS. HosmaneN. S. Effects of Linkers on the Development of Liposomal Formulation of Cholesterol Conjugated Cobalt Bis(Dicarbollides).J. Pharm. Sci.202111031365137310.1016/j.xphs.2020.12.017
     [Google Scholar]
  15. DubeyR. D. SanejaA. QayumA. SinghA. MahajanG. ChashooG. KumarA. AndotraS. S. SinghS. K. SinghG. KoulS. MondheD. M. GuptaP. N. PLGA Nanoparticles Augmented the Anticancer Potential of Pentacyclic Triterpenediol: In vivo in Mice.RSC Adv.2016678745867459710.1039/c6ra14929d
     [Google Scholar]
  16. NahireR. HaldarM. K. PaulS. AmbreA. H. MeghnaniV. LayekB. KattiK. S. GangeK. N. SinghJ. SarkarK. MallikS. Multifunctional Polymersomes for Cytosolic Delivery of Gemcitabine and Doxorubicin to Cancer Cells.Biomaterials201435246482649710.1016/j.biomaterials.2014.04.026
     [Google Scholar]
  17. WangY. FanW. DaiX. KatragaddaU. McKinleyD. TengQ. TanC. Enhanced Tumor Delivery of Gemcitabine via PEGDSPE/TPGS Mixed Micelles.Mol. Pharm.20141141140115010.1021/mp4005904
     [Google Scholar]
  18. JiaL. ZhengJ. J. JiangS. M. HuangK. H. Preparation, Physicochemical Characterization and Cytotoxicity in vitro of Gemcitabine-Loaded PEG-PDLLA Nanovesicles.World J. Gastroenterol.20101681008101310.3748/wjg.v16.i8.1008
     [Google Scholar]
  19. DubeyR. D. KlippsteinR. WangJ. T. W. HodginsN. MeiK. C. SosabowskiJ. HiderR. C. AbbateV. GuptaP. N. Al-JamalK. T. Novel Hyaluronic Acid Conjugates for Dual Nuclear Imaging and Therapy in Cd44-Expressing Tumors in Mice in vivo.Nanotheranostics201711597910.7150/ntno.17896
     [Google Scholar]
  20. ParohaS. VermaJ. Singh ChandelA. K. KumariS. RaniL. DubeyR. D. MahtoA. K. PandaA. K. SahooP. K. DewanganR. P. Augmented Therapeutic Efficacy of Gemcitabine Conjugated Self-Assembled Nanoparticles for Cancer Chemotherapy.J. Drug Deliv. Sci. Technol.20227610379610.1016/J.JDDST.2022.103796
     [Google Scholar]
  21. ChenZ. ChenJ. WuL. LiW. ChenJ. ChengH. PanJ. CaiB. Hyaluronic Acid-Coated Bovine Serum Albumin Nanoparticles Loaded with Brucine as Selective Nanovectors for Intra-Articular Injection.Int. J. Nanomedicine201383843385310.2147/IJN.S50721
     [Google Scholar]
  22. KumarR. SinghM. MeenaJ. SinghviP. ThiyagarajanD. SanejaA. PandaA. K. Hyaluronic Acid - Dihydroartemisinin Conjugate: Synthesis, Characterization and in vitro Evaluation in Lung Cancer Cells.Int. J. Biol. Macromol.201913349550210.1016/j.ijbiomac.2019.04.124
     [Google Scholar]
  23. LiJ. M. ChenW. WangH. JinC. YuX. J. LuW. Y. CuiL. FuD. L. NiQ. X. HouH. M. Preparation of Albumin Nanospheres Loaded with Gemcitabine and Their Cytotoxicity against BXPC-3 Cells in vitro.Acta Pharmacol. Sin.20093091337134310.1038/aps.2009.125
     [Google Scholar]
  24. QiS. JW. McAuley YangZ. TipduangtaP. Physical Stabilization of Low-Molecular- Weight Amorphous Drugs in the Solid State: A Material Science Approach.Ther. Deliv.20145781784110.4155/tde.14.39
     [Google Scholar]
  25. GuptaA. AsthanaS. KonwarR. ChourasiaM. K. An Insight into Potential of Nanoparticles-Assisted Chemotherapy of Cancer Using Gemcitabine and Its Fatty Acid Prodrug: A Comparative Study.J. Biomed. Nanotechnol.20139591592510.1166/jbn.2013.1591
     [Google Scholar]
  26. BarefordL. M. SwaanP. W. Endocytic Mechanisms for Targeted Drug Delivery.Adv. Drug Deliv. Rev.200759874875810.1016/j.addr.2007.06.008
     [Google Scholar]
  27. VandanaM. SahooS. K. Long Circulation and Cytotoxicity of PEGylated Gemcitabine and Its Potential for the Treatment of Pancreatic Cancer.Biomaterials201031359340935610.1016/j.biomaterials.2010.08.010
     [Google Scholar]
  28. GiovannettiE. LeonL. G. BertiniS. MacChiaM. MinutoloF. FunelN. AlecciC. GiancolaF. DanesiR. PetersG. J. Study of Apoptosis Induction and Deoxycytidine Kinase/Cytidine Deaminase Modulation in the Synergistic Interaction of a Novel Ceramide Analog and Gemcitabine in Pancreatic Cancer Cells.Nucleosides, Nucleotides and Nucleic Acids2010294-641942610.1080/15257771003730193
     [Google Scholar]
  29. AbbruzzeseJ. L. GrunewaldR. KantarjianH. DuM. FaucherK. TarossoffP. PlunkettW. Gemcitabine in Leukemia: A Phase I Clinical, Plasma, and Cellular Pharmacology Study.J. Clin. Oncol.199210340641310.1200/jco.1992.10.3.406
     [Google Scholar]
  30. MeyV. GiovannettiE. De BraudF. NannizziS. CuriglianoG. VerweijF. De CobelliO. PeceS. Del TaccaM. DanesiR. In vitro Synergistic Cytotoxicity of Gemcitabine and Pemetrexed and Pharmacogenetic Evaluation of Response to Gemcitabine in Bladder Cancer Patients.Br. J. Cancer200695328929710.1038/sj.bjc.6603242
     [Google Scholar]
  31. BermanP. A. AdamsP. A. Artemisinin Enhances Heme-Catalysed Oxidation of Lipid Membranes.Free Radic. Biol. Med.19972271283128810.1016/S0891‑5849(96)00508‑4
     [Google Scholar]
/content/journals/cdd/10.2174/0115672018317615240926163652
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Fabrication and Evaluation of Hyaluronic Acid-Coated Albumin Nanoparticles for Delivery of Gemcitabine
Curr. Drug Deliv. 22, 1430 (2025); https://doi.org/10.2174/0115672018317615240926163652
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  • Article Type:     Research Article
Keyword(s): anticancer; bovine serum albumin; CD44 receptor; cytotoxicity; Gemcitabine; hyaluronic acid; mitochondrial membrane potential; nanoparticles

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