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2000
Volume 26, Issue 4
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Background

Carboplatin (CP) is a widely used chemotherapeutic agent with poor oral bioavailability and potential systemic toxicity when administered intravenously. There is a growing interest in developing sustained-release oral formulations to improve therapeutic efficacy and patient compliance.

Objective

The present study aimed to develop and evaluate an oral, enteric-coated, PEGylated multi-walled carbon nanotube (MWCNT) formulation (F2) of carboplatin and assess its pharmacokinetic and histopathological profile in comparison with the marketed intravenous product, Kemocarb®.

Methods

A sensitive and robust HPLC method was developed for the quantification of CP in rabbit plasma. Stability studies were performed at 4 °C for 4 hours and -80°C for 4 weeks. Histopathological evaluation was conducted on major organs of mice to assess toxicity. CP and caffeine were extracted with minimal matrix interference. Pharmacokinetic studies were performed following oral administration of the F2 formulation and compared with Kemocarb®.

Results

The developed HPLC method demonstrated good sensitivity, accuracy, and robustness. CP was stable under both short-term and long-term storage conditions. Histological analysis revealed no significant pathological damage in mice organs. The F2 formulation exhibited sustained drug release for up to 24 hours. The Tmax, Cmax, and MRT of CP for F2 were different compared to Kemocarb®, with a relative bioavailability of 1.182 ± 0.24. The Cmax and MRT of F2 were 12.327 ± 0.03* and 3.5805 ± 0.26 h, respectively.

Conclusion

The developed F2 formulation of carboplatin demonstrates sustained release and improved relative bioavailability following oral administration. It may offer a promising alternative to commercial intravenous CP injections (Kemocarb®), potentially supporting metronomic chemotherapy strategies with improved patient compliance and reduced systemic toxicity.

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2025-07-22
2026-02-02

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References

  1. HarlandS.J. NewellD.R. SiddikZ.H. ChadwickR. CalvertA.H. HarrapK.R. Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function.Cancer Res.198444416931697 6367971
     [Google Scholar]
  2. ElmorsyE.A. SaberS. HamadR.S. Abdel-ReheimM.A. El-kottA.F. AlShehriM.A. MorsyK. SalamaS.A. YoussefM.E. Advances in understanding cisplatin-induced toxicity: Molecular mechanisms and protective strategies.Eur. J. Pharm. Sci.202420310693910.1016/j.ejps.2024.106939 39423903
     [Google Scholar]
  3. DasariS. Bernard TchounwouP. Cisplatin in cancer therapy: Molecular mechanisms of action.Eur. J. Pharmacol.201474036437810.1016/j.ejphar.2014.07.025 25058905
     [Google Scholar]
  4. HwaYun. B.; Guo, J.; Bellamri, M.; Turesky, R.J. DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans.Mass Spectrom. Rev.2020391-2558210.1002/mas.21570 29889312
     [Google Scholar]
  5. DoolittleN.D. MuldoonL.L. CulpA.Y. NeuweltE.A. Delivery of Chemotherapeutics Across the Blood–Brain Barrier.Advances in Pharmacology.Elsevier201420324310.1016/bs.apha.2014.06.002
     [Google Scholar]
  6. ChengY. WuR. ChengM. DuJ. HuX. YuL. ZhaoX. YaoY. LongQ. ZhuL. ZhuJ. HuangN. LiuH. HuY. WanF. Carboplatin-induced hematotoxicity among patients with non-small cell lung cancer: Analysis on clinical adverse events and drug-gene interactions.Oncotarget2017819322283223610.18632/oncotarget.12951 27802181
     [Google Scholar]
  7. NguyenS.M. PhamA.T. NguyenL.M. CaiH. TranT.V. ShuX.O. TranH.T.T. Chemotherapy-Induced Toxicities and Their Associations with Clinical and Non-Clinical Factors among Breast Cancer Patients in Vietnam.Curr. Oncol.202229118269828410.3390/curroncol29110653 36354713
     [Google Scholar]
  8. PasquierE. KavallarisM. AndréN. Metronomic chemotherapy: New rationale for new directions.Nat. Rev. Clin. Oncol.20107845546510.1038/nrclinonc.2010.82 20531380
     [Google Scholar]
  9. SimsekC. EsinE. YalcinS. Metronomic chemotherapy: A systematic review of the literature and clinical experience.J. Oncol.2019201913110.1155/2019/5483791 31015835
     [Google Scholar]
  10. SharmaS. NaskarS. KuotsuK. Metronomic chemotherapy of carboplatin-loaded PEGylated MWCNTs: Synthesis, characterization and in vitro toxicity in human breast cancer.Carbon Letters202030443544710.1007/s42823‑019‑00113‑0
     [Google Scholar]
  11. YamazakiH. TanakaK. GamuraS. HashimotoT. ShimizuM. High-performance liquid chromatographic assay for carboplatin in ultrafiltered plasma combined with hyperbaric oxygenation.Drug Metab. Pharmacokinet.200621542943110.2133/dmpk.21.429 17072097
     [Google Scholar]
  12. BalesJ.R. CoulsonC.J. GilmourD.W. MazidM.A. NeidleS. KurodaR. PeartB.J. RamsdenC.A. SadlerP.J. The preparation and isomerization of platinum metronidazole complexes: X-ray crystal and molecular structures of cis- and trans-dichlorobis[1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole]-platinum(II).J. Chem. Soc. Chem. Commun.1983432843210.1039/c39830000432
     [Google Scholar]
  13. KloftC. AppeliusH. SiegertW. SchunackW. JaehdeU. Determination of platinum complexes in clinical samples by a rapid flameless atomic absorption spectrometry assay.Ther. Drug Monit.199921663163710.1097/00007691‑199912000‑00009 10604824
     [Google Scholar]
  14. CurisE. ProvostK. BouvetD. NicolisI. Crauste-MancietS. BrossardD. BénazethS. Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS.J. Synchrotron Radiat.20018271671810.1107/S0909049500017775 11512906
     [Google Scholar]
  15. MorrisonJ.G. WhiteP. McDougallS. FirthJ.W. WoolfreyS.G. GrahamM.A. GreensladeD. Validation of a highly sensitive ICP-MS method for the determination of platinum in biofluids: Application to clinical pharmacokinetic studies with oxaliplatin.J. Pharm. Biomed. Anal.200024111010.1016/S0731‑7085(00)00377‑0 11108533
     [Google Scholar]
  16. HrichiH. KoukiN. TarH. Analytical methods for the quantification of cisplatin, carboplatin, and oxaliplatin in various matrices over the last two decades.Curr. Pharm. Anal.202218545549010.2174/1573412918666210929105058
     [Google Scholar]
  17. BurnsR.B. EmbreeL. Validation of high-performance liquid chromatographic assay methods for the analysis of carboplatin in plasma ultrafiltrate.J. Chromatogr., Biomed. Appl.2000744236737610.1016/S0378‑4347(00)00262‑0 10993526
     [Google Scholar]
  18. ItoH. YamaguchiH. FujikawaA. ShiidaN. TanakaN. OguraJ. KobayashiM. YamadaT. ManoN. IsekiK. Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.2013917-918182310.1016/j.jchromb.2012.11.024 23348368
     [Google Scholar]
  19. JohnstoneT.C. SuntharalingamK. LippardS.J. The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs.Chem. Rev.201611653436348610.1021/acs.chemrev.5b00597 26865551
     [Google Scholar]
  20. KharissovaO.V. KharisovB.I. de Casas OrtizE.G. Dispersion of carbon nanotubes in water and non-aqueous solvents.RSC Advances20133472481210.1039/c3ra43852j
     [Google Scholar]
  21. SalamM.A. BurkR. Synthesis and characterization of multi-walled carbon nanotubes modified with octadecylamine and polyethylene glycol.Arab. J. Chem.201710S921S92710.1016/j.arabjc.2012.12.028
     [Google Scholar]
  22. WuH. ShiH. ZhangH. WangX. YangY. YuC. HaoC. DuJ. HuH. YangS. Prostate stem cell antigen antibody-conjugated multiwalled carbon nanotubes for targeted ultrasound imaging and drug delivery.Biomaterials201435205369538010.1016/j.biomaterials.2014.03.038 24709520
     [Google Scholar]
  23. SharmaS. SarkarG. SresthaB. ChattopadhyayD. BhowmikM. In-situ fast gelling formulation for oral sustained drug delivery of paracetamol to dysphagic patients.Int. J. Biol. Macromol.201913486486810.1016/j.ijbiomac.2019.05.092 31102679
     [Google Scholar]
  24. AlexA.T. JosephA. ShaviG. RaoJ.V. UdupaN. Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery.Drug Deliv.20162372144215310.3109/10717544.2014.948643 25544603
     [Google Scholar]
  25. MittalA. ChitkaraD. KumarN. HPLC method for the determination of carboplatin and paclitaxel with cremophorEL in an amphiphilic polymer matrix.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.2007855221121910.1016/j.jchromb.2007.05.005 17543592
     [Google Scholar]
  26. MatsumuraS. AjimaK. YudasakaM. IijimaS. ShibaK. Dispersion of cisplatin-loaded carbon nanohorns with a conjugate comprised of an artificial peptide aptamer and polyethylene glycol.Mol. Pharm.20074572372910.1021/mp070022t 17685580
     [Google Scholar]
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Oral Metronomic Formulation of Carboplatin Loaded PEGylated- MWCNTs: HPLC Method Validation and Pharmacokinetic Studies in Rabbit’s Plasma
Current Drug Metabolism 26, 281 (2025); https://doi.org/10.2174/0113892002378541250704181148
/content/journals/cdm/10.2174/0113892002378541250704181148
/content/journals/cdm/10.2174/0113892002378541250704181148
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  • Article Type:     Research Article
Keyword(s): Carboplatin; gastric degradation; method validation; metronomic chemotherapy; multiwall carbon nanotubes; pharmacokinetics

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