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

Abstract

Introduction

DSPE-mPEG2000 is a phospholipid and polyethylene glycol conjugate used in various biomedical applications, including drug delivery, gene transfection, and vaccine delivery. Due to the hydrophilic and hydrophobic properties of DSPE-mPEG2000, it can serve as a drug carrier, encapsulating drugs in liposomes to enhance stability and efficacy.

Methods

In this study, long-circulating podophyllotoxin liposomes (Lc-PTOX-Lps) were prepared using DSPE-mPEG2000 as a modifying material and evaluated for their pharmacokinetics and anticancer activity.

Results

Lc-PTOX-Lps had an encapsulation rate of 87.11±1.77%, an average particle size of 168.91±7.07 nm, a polydispersity index (PDI) of 0.19±0.04, and a zeta potential of -24.37±0.36 mV. release studies showed that Lc-PTOX-Lps exhibited a significant slow-release effect. The long-circulating liposomes demonstrated better stability compared to normal liposomes and exhibited a significant slow-release profile. Pharmacokinetic studies indicated that Lc-PTOX-Lps had a prolonged half-life, reduced clearance, and improved bioavailability. Additionally, Lc-PTOX-Lps exhibited better anticancer effects on MCF-7 cells and lower toxicity to normal cells compared to PTOX.

Conclusion

Lc-PTOX-Lps were synthesized using a simple and effective method, and Lc-PTOX-Lps are promising anticancer agents.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018356666241224052638
2025-01-02
2025-12-26

  • From This Site

    /content/journals/cdd/10.2174/0115672018356666241224052638
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. ShahZ. GoharU.F. JamshedI. MushtaqA. MukhtarH. HaqZ.U.M. TomaS.I. ManeaR. MogaM. PopoviciB. Podophyllotoxin: History, recent advances and future prospects.Biomolecules202111460310.3390/biom1104060333921719
     [Google Scholar]
  2. GordalizaM. GarcíaP.A. CorralM.D.J.M. CastroM.A. ZuritaG.M.A. Podophyllotoxin: Distribution, sources, applications and new cytotoxic derivatives.Toxicon200444444145910.1016/j.toxicon.2004.05.00815302526
     [Google Scholar]
  3. MotykaS. JafernikK. EkiertH. RadS.J. CalinaD. Al-OmariB. SzopaA. ChoW.C. Podophyllotoxin and its derivatives: Potential anticancer agents of natural origin in cancer chemotherapy.Biomed. Pharmacother.202315811414510.1016/j.biopha.2022.11414536586242
     [Google Scholar]
  4. CuiQ. DuR. LiuM. RongL. Lignans and their derivatives from plants as antivirals.Molecules202025118310.3390/molecules2501018331906391
     [Google Scholar]
  5. ShiR. FanH. YuX. TangY. JiangJ. LiangX. Advances of podophyllotoxin and its derivatives: Patterns and mechanisms.Biochem. Pharmacol.202220011503910.1016/j.bcp.2022.11503935436465
     [Google Scholar]
  6. ArdalaniH. AvanA. MobarhanG.M. Podophyllotoxin: A novel potential natural anticancer agent.Avicenna J. Phytomed.201774285294[PMID: 28884079
     [Google Scholar]
  7. FanH. ZhuZ. XianH. WangH. ChenB. TangY.J. TangY. LiangX. Insight into the molecular mechanism of podophyllotoxin derivatives as anticancer drugs.Front. Cell Dev. Biol.2021970907510.3389/fcell.2021.70907534447752
     [Google Scholar]
  8. YuX. CheZ. XuH. Recent advances in the chemistry and biology of podophyllotoxins.Chemistry201723194467452610.1002/chem.20160247227726183
     [Google Scholar]
  9. SunW. SunF. MengJ. CaoX. ZhaoS. WangC. LiL. JiangP. Design, semi-synthesis and bioactivity evaluation of novel podophyllotoxin derivatives as potent anti-tumor agents.Bioorg. Chem.202212610590610.1016/j.bioorg.2022.10590635661529
     [Google Scholar]
  10. ShenS. TongY. LuoY. HuangL. GaoW. Biosynthesis, total synthesis, and pharmacological activities of aryltetralin-type lignan podophyllotoxin and its derivatives.Nat. Prod. Rep.20223991856187510.1039/D2NP00028H35913409
     [Google Scholar]
  11. YinM. FangY. SunX. XueM. ZhangC. ZhuZ. MengY. KongL. MyintY.Y. LiY. ZhaoJ. YangX. Synthesis and anticancer activity of podophyllotoxin derivatives with nitrogen-containing heterocycles.Front Chem.202311119149810.3389/fchem.2023.119149837234201
     [Google Scholar]
  12. YakkalaP.A. PenumalluN.R. ShafiS. KamalA. Prospects of topoisomerase inhibitors as promising anti-cancer agents.Pharmaceuticals20231610145610.3390/ph1610145637895927
     [Google Scholar]
  13. AbdelwahedW. DegobertG. StainmesseS. FessiH. Freeze-drying of nanoparticles: Formulation, process and storage considerations.Adv. Drug Deliv. Rev.200658151688171310.1016/j.addr.2006.09.01717118485
     [Google Scholar]
  14. AljamalW. KostarelosK. Construction of nanoscale multicompartment liposomes for combinatory drug delivery.Int. J. Pharm.2007331218218510.1016/j.ijpharm.2006.11.02017223294
     [Google Scholar]
  15. GuimarãesD. PauloC.A. NogueiraE. Design of liposomes as drug delivery system for therapeutic applications.Int. J. Pharm.202160112057110.1016/j.ijpharm.2021.12057133812967
     [Google Scholar]
  16. LingL. YaoC. DuY. IsmailM. HeR. HouY. ZhangY. LiX. Assembled liposomes of dual podophyllotoxin phospholipid: Preparation, characterization and in vivo anticancer activity.Nanomedicine201712665767210.2217/nnm‑2016‑039628244817
     [Google Scholar]
  17. ZhaoX. QiuN. MaY. LiuJ. AnL. ZhangT. LiZ. HanX. ChenL. Preparation, characterization and biological evaluation of β-cyclodextrin-biotin conjugate based podophyllotoxin complex.Eur. J. Pharm. Sci.202116010574510.1016/j.ejps.2021.10574533549707
     [Google Scholar]
  18. LiM. ZhaoY. SunJ. ChenH. LiuZ. LinK. MaP. ZhangW. ZhenY. ZhangS. ZhangS. pH/reduction dual-responsive hyaluronic acid-podophyllotoxin prodrug micelles for tumor targeted delivery.Carbohydr. Polym.202228811940210.1016/j.carbpol.2022.11940235450654
     [Google Scholar]
  19. LiY. XuP. HeD. XuB. TuJ. ShenY. Long-circulating thermosensitive liposomes for the targeted drug delivery of oxaliplatin.Int. J. Nanomedicine2020156721673410.2147/IJN.S25077332982229
     [Google Scholar]
  20. CaddeoC. PucciL. GabrieleM. CarboneC. BusquetsF.X. ValentiD. PonsR. VassalloA. FaddaA.M. ManconiM. Stability, biocompatibility and antioxidant activity of PEG-modified liposomes containing resveratrol.Int. J. Pharm.20185381-2404710.1016/j.ijpharm.2017.12.04729294324
     [Google Scholar]
  21. DeodharS. DashA.K. Long circulating liposomes: Challenges and opportunities.Ther. Deliv.201891285787210.4155/tde‑2018‑003530444455
     [Google Scholar]
  22. TiwariH. RaiN. SinghS. GuptaP. VermaA. SinghA.K. Kajal; Salvi, P.; Singh, S.K.; Gautam, V. Recent advances in nanomaterials-based targeted drug delivery for preclinical cancer diagnosis and therapeutics.Bioengineering202310776010.3390/bioengineering1007076037508788
     [Google Scholar]
  23. TenchovR. SassoJ.M. ZhouQ.A. PEGylated lipid nanoparticle formulations: Immunological safety and efficiency perspective.Bioconjug. Chem.202334694196010.1021/acs.bioconjchem.3c0017437162501
     [Google Scholar]
  24. MadkhaliO.A. Perspectives and prospective on solid lipid nanoparticles as drug delivery systems.Molecules2022275154310.3390/molecules2705154335268643
     [Google Scholar]
  25. DrummondD.C. NobleC.O. HayesM.E. ParkJ.W. KirpotinD.B. Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development.J. Pharm. Sci.200897114696474010.1002/jps.2135818351638
     [Google Scholar]
  26. ArakachiO.K. HerculanoM.J. JuradoR. MuniveL.M. LopezG.P. Pharmacokinetics and anti-tumor efficacy of pegylated liposomes co-loaded with cisplatin and mifepristone.Pharmaceuticals20231610133710.3390/ph1610133737895808
     [Google Scholar]
  27. LawrieT.A. RabbieR. ThomaC. MorrisonJ. Pegylated liposomal doxorubicin for first-line treatment of epithelial ovarian cancer.Cochrane Database Syst. Rev.2013201310CD01048210.1002/14651858.CD010482.pub224142521
     [Google Scholar]
  28. MohamedN.A. MareiI. CrovellaS. SalehA.H. Recent developments in nanomaterials-based drug delivery and upgrading treatment of cardiovascular diseases.Int. J. Mol. Sci.2022233140410.3390/ijms2303140435163328
     [Google Scholar]
  29. SeoY. LimH. ParkH. YuJ. AnJ. YooH.Y. LeeT. Recent progress of lipid nanoparticles-based lipophilic drug delivery: Focus on surface modifications.Pharmaceutics202315377210.3390/pharmaceutics1503077236986633
     [Google Scholar]
  30. YinL. PangY. ShanL. GuJ. The in vivo pharmacokinetics of block copolymers containing polyethylene glycol used in nanocarrier drug delivery systems.Drug Metab. Dispos.202250682783610.1124/dmd.121.00056835066464
     [Google Scholar]
  31. SugarbakerP.H. StuartO.A. Pharmacokinetics of the intraperitoneal nanoparticle pegylated liposomal doxorubicin in patients with peritoneal metastases.Eur. J. Surg. Oncol.202147110811410.1016/j.ejso.2019.03.03530954354
     [Google Scholar]
  32. MolesE. HowardC.B. HudaP. KarsaM. McCalmontH. KimptonK. DulyA. ChenY. HuangY. TurskyM.L. MaD. BustamanteS. PickfordR. ConnertyP. OmariS. JollyC.J. JoshiS. ShenS. PimandaJ.E. DolnikovA. CheungL.C. KotechaR.S. NorrisM.D. HaberM. de BockC.E. SomersK. LockR.B. ThurechtK.J. KavallarisM. Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia.Sci. Transl. Med.202315696eabm126210.1126/scitranslmed.abm126237196067
     [Google Scholar]
  33. BakiC. Bone marrow targeted liposomal drug delivery systems..Middle East Technical University2011https://etd.lib.metu.edu.tr/upload/12613251/index.pdf
     [Google Scholar]
  34. ShiF. YinW. FrimpongA.M. LiX. XiaX. SunW. JiH. ToreniyazovE. QilongW. CaoX. YuJ. XuX. In-vitro and in-vivo evaluation and anti-colitis activity of esculetin-loaded nanostructured lipid carrier decorated with DSPE-MPEG2000.J. Microencapsul.202340644245510.1080/02652048.2023.221534537191893
     [Google Scholar]
  35. ChouT.H. ChuI.M. Thermodynamic characteristics of DSPC/DSPE-PEG2000 mixed monolayers on the water subphase at different temperatures.Colloids Surf. B Biointerfaces200327433334410.1016/S0927‑7765(02)00096‑6
     [Google Scholar]
  36. ZhangX.Y. QiaoH. ShiY.B. HPLC method with fluorescence detection for the determination of ligustilide in rat plasma and its pharmacokinetics.Pharm. Biol.2014521213010.3109/13880209.2013.80579024044763
     [Google Scholar]
  37. DesbèneS. RenaultG.S. Drugs that inhibit tubulin polymerization: The particular case of podophyllotoxin and analogues.Curr. Med. Chem. Anticancer Agents201221719010.2174/156801102335435312678752
     [Google Scholar]
  38. LeeS.O. JooS.H. KwakA.W. LeeM.H. SeoJ.H. ChoS.S. YoonG. ChaeJ.I. ShimJ.H. Podophyllotoxin induces ROS-mediated apoptosis and cell cycle arrest in human colorectal cancer cells via p38 MAPK signaling.Biomol. Ther.202129665866610.4062/biomolther.2021.14334642263
     [Google Scholar]
  39. AkhtarM.J. YarM.S. KhanA.A. AliZ. HaiderM.R. Recent advances in the synthesis and anticancer activity of some molecules other than nitrogen containing heterocyclic moeities.Mini Rev. Med. Chem.201717171602163210.2174/138955751666616103112163927804888
     [Google Scholar]
  40. ShakerS. GardouhA. GhorabM. Factors affecting liposomes particle size prepared by ethanol injection method.Res. Pharm. Sci.201712534635210.4103/1735‑5362.21397928974972
     [Google Scholar]
  41. WangJ. SuoX. ZhangH. P-glycoprotein antibody-conjugated paclitaxel liposomes targeted for multidrug-resistant lung cancer.Nanomedicine2023181081983110.2217/nnm‑2023‑001537306214
     [Google Scholar]
  42. ShangguanY. NiJ. JiangL. HuY. HeC. MaY. WuG. XiongH. Response surface methodology-optimized extraction of flavonoids from pomelo peels and isolation of naringin with antioxidant activities by Sephadex LH20 gel chromatography.Curr. Res. Food Sci.2023710061010.1016/j.crfs.2023.10061037860143
     [Google Scholar]
/content/journals/cdd/10.2174/0115672018356666241224052638
Loading
DSPE-mPEG2000-Modified Podophyllotoxin Long-Circulating Liposomes for Targeted Delivery: Their Preparation, Characterization, and Evaluation
Curr. Drug Deliv. 22, 1481 (2025); https://doi.org/10.2174/0115672018356666241224052638
/content/journals/cdd/10.2174/0115672018356666241224052638
/content/journals/cdd/10.2174/0115672018356666241224052638
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): breast cancer; cancer therapy; DSPE-mPEG2000; liposomes; pharmacokinetics; Podophyllotoxin; stability

Most Cited Most Cited RSS feed

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