Skip to main content

Advertisement

SpringerLink
Log in

Umbelliferone loaded PEGylated liposomes: preparation, characterization and its mitigatory effects on Dalton’s ascites lymphoma development

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Umbelliferone (UB) is a phenylpropanoid-based pharmacologically active agent with promising anti-tumor activities. However, complete elucidation of its therapeutic efficacy remains challenging due to low solubility and bioavailability. The present study aimed to develop a liposomal delivery system for UB to enhance its therapeutic efficacy against Dalton’s ascites lymphoma tumor model. Umbelliferone-encapsulated nanoliposomes (nLUB) were prepared using the thin-film hydration method and performed a series of characterizations to confirm successful development. The nLUB showed a particle size of 116 ± 3.2 nm with a negative surface charge and encapsulation efficiency of 78%. In vitro study results showed that nLUB treatment significantly enhanced cellular uptake and apoptosis induction in lymphoma cells compared to free UB. nLUB treatment significantly stabilized body weight, reduced tumor growth, and improved the serum biochemical and hematological parameters of experimental animals, thereby improving their overall survivability compared to an free UB. Our result indicates that nanoencapsulation enhanced the therapeutic potential of UB, which may find its way to clinical application in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data will be available on request.

References

  • Abeesh P, Vishnu WK, Guruvayoorappan C (2021) Preparation and characterization of withaferin A loaded pegylated nanoliposomal formulation with high loading efficacy: in vitro and in vivo anti-tumour study. Mater Sci Eng C 128:112335

    Article  CAS  Google Scholar 

  • Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48

    Article  CAS  PubMed  Google Scholar 

  • Cruz LF, de Figueiredo GF, Pedro LP, Amorin YM, Andrade JT, Passos TF, Rodrigues FF, Souza ILA, Gonçalves TPR, dos Santos Lima LAR (2020) Umbelliferone (7-hydroxycoumarin): a non-toxic antidiarrheal and antiulcerogenic coumarin. Biomed Pharmacother 129:110432

    Article  CAS  PubMed  Google Scholar 

  • Damari SP, Shamrakov D, Varenik M, Koren E, Nativ-Roth E, Barenholz Y, Regev O (2018) Practical aspects in size and morphology characterization of drug-loaded nano-liposomes. Int J Pharm 547(1–2):648–655

    Article  Google Scholar 

  • Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari M (2018) Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2):57

    Article  PubMed  PubMed Central  Google Scholar 

  • Dhamija I, Kumar N, Manjula S, Parihar V, Setty MM, Pai K (2013) Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Premna herbacea Roxb. in Ehrlich ascites carcinoma model and Dalton’s lymphoma ascites model. Exp Toxicol Pathol 65(3):235–242

    Article  CAS  PubMed  Google Scholar 

  • Dong H, Parekh HS, Xu ZP (2015) Particle size-and number-dependent delivery to cells by layered double hydroxide nanoparticles. J Colloid Interface Sci 437:10–16

    Article  CAS  PubMed  Google Scholar 

  • Evans BC, Nelson CE, Shann SY, Beavers KR, Kim AJ, Li H, Nelson HM, Giorgio TD, Duvall CL (2013) Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. JoVE 73:e50166

    Google Scholar 

  • Guruvayoorappan C, Kuttan G (2007) Immunomodulatory and antitumor activity of Biophytum sensitivum extract. Asian Pac J Cancer Prev 8(1):27

    CAS  PubMed  Google Scholar 

  • He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31(13):3657–3666

    Article  CAS  PubMed  Google Scholar 

  • Heurtault B, Saulnier P, Pech B, Proust J-E, Benoit J-P (2003) Physico-chemical stability of colloidal lipid particles. Biomaterials 24(23):4283–4300

    Article  CAS  PubMed  Google Scholar 

  • Iglesias-Montes ML, Luzi F, Dominici F, Torre L, Manfredi LB, Cyras VP, Puglia D (2021) Migration and degradation in composting environment of active polylactic acid bilayer nanocomposites films: combined role of umbelliferone, lignin and cellulose nanostructures. Polymers 13(2):282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomed 1(3):297

    CAS  Google Scholar 

  • Kang TH, Mao C-P, He L, Tsai Y-C, Liu K, La V, Wu T-C, Hung C-F (2012) Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects. PLoS ONE 7(4):e35141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kang C, Sun Y, Zhu J, Li W, Zhang A, Kuang T, Xie J, Yang ZJCDM (2016) Delivery of nanoparticles for treatment of brain tumor. Curr Drug Metab 17(8):745–754

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Bhatt PC, Rahman M, Kaithwas G, Choudhry H, Al-Abbasi FA, Anwar F, Verma A (2017) Fabrication, optimization, and characterization of umbelliferone β-d-galactopyranoside-loaded PLGA nanoparticles in treatment of hepatocellular carcinoma: in vitro and in vivo studies. Int J Nanomed 12:6747

    Article  CAS  Google Scholar 

  • Kundu M, Chatterjee S, Ghosh N, Manna P, Das J, Sil PC (2020) Tumor targeted delivery of umbelliferone via a smart mesoporous silica nanoparticles controlled-release drug delivery system for increased anticancer efficiency. Mater Sci Eng C 116:111239

    Article  CAS  Google Scholar 

  • Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ (2004) Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer 43(3):275–283

    Article  PubMed  Google Scholar 

  • Lu T, Haemmerich D, Liu H, Seynhaeve AL, van Rhoon GC, Houtsmuller AB, Ten Hagen TL (2021) Externally triggered smart drug delivery system encapsulating idarubicin shows superior kinetics and enhances tumoral drug uptake and response. Theranostics 11(12):5700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muthu R, Thangavel P, Selvaraj N, Ramalingam R, Vaiyapuri M (2013) Synergistic and individual effects of umbelliferone with 5-flurouracil on the status of lipid peroxidation and antioxidant defense against 1, 2-dimethylhydrazine induced rat colon carcinogenesis. Biomed Prev Nutr 3(1):74–82

    Article  Google Scholar 

  • Priya R, Ilavenil S, Kaleeswaran B, Srigopalram S, Ravikumar S (2011) Effect of Lawsonia inermis on tumor expression induced by Dalton’s lymphoma ascites in Swiss albino mice. Saudi J Biol Sci 18(4):353–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramesh B, Pugalendi K (2006) Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats. J Med Food 9(4):562–566

    Article  CAS  PubMed  Google Scholar 

  • Ramu R, S. Shirahatti P, Zameer F, Lakkappa Dhananjaya B, MN NP, (2016) Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp. Var. Nanjangud Rasa Bale) flower in hyperglycaemic rodent model. PLoS ONE 11(3):e0151135

    Article  PubMed  PubMed Central  Google Scholar 

  • Rauf A, Khan R, Khan H, Pervez S, Pirzada AS (2014) In vivo antinociceptive and anti-inflammatory activities of umbelliferone isolated from Potentilla evestita. Nat Prod Res 28(17):1371–1374

    Article  CAS  PubMed  Google Scholar 

  • Sakthivel K, Kannan N, Angeline A, Guruvayoorappan C (2012) Anticancer activity of Acacia nilotica (L.) Wild. Ex. Delile subsp. indica against Dalton’s ascitic lymphoma induced solid and ascitic tumor model. Asian Pac J Cancer Prev 13(8):3989–3995

    Article  CAS  PubMed  Google Scholar 

  • Sarabandi K, Jafari SM, Mohammadi M, Akbarbaglu Z, Pezeshki A, Heshmati MK (2019) Production of reconstitutable nanoliposomes loaded with flaxseed protein hydrolysates: stability and characterization. Food Hydrocolloids 96:442–450

    Article  CAS  Google Scholar 

  • Shi Y, Van der Meel R, Chen X, Lammers T (2020) The EPR effect and beyond: strategies to improve tumor targeting and cancer nanomedicine treatment efficacy. Theranostics 10(17):7921

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh R, Lillard JWJE Jr (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86(3):215–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh D, Rahman M (2020) Umbelliferone loaded nanocarriers for healthcare applications. Curr Biochem Eng 6(1):25–33

    Article  CAS  Google Scholar 

  • Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99:28–51

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Kang C, Wang M, Zhu J, Jin L, Cheng X (2016) Nanosized camptothecin conjugates for single and combined drug delivery. Eur J BioMed Res 2:8–16

    Article  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clinicians 71(3):209–249

    Article  Google Scholar 

  • Telange DR, Nirgulkar SB, Umekar MJ, Patil AT, Pethe AM, Bali NR (2019) Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: formulation development, physico-chemical and functional characterization. Eur J Pharm Sci 131:23–38

    Article  CAS  PubMed  Google Scholar 

  • Ullah S, Shah MR, Shoaib M, Imran M, Elhissi AM, Ahmad F, Ali I, Shah SWA (2016) Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin. Drug Deliv 23(9):3480–3491

    Article  CAS  PubMed  Google Scholar 

  • Vasconcelos JF, Teixeira MM, Barbosa-Filho JM, Agra MF, Nunes XP, Giulietti AM, Ribeiro-dos-Santos R, Soares MB (2009) Effects of umbelliferone in a murine model of allergic airway inflammation. Eur J Pharmacol 609(1–3):126–131

    Article  CAS  PubMed  Google Scholar 

  • Vijayalakshmi A, Sindhu G (2017) Umbelliferone arrest cell cycle at G0/G1 phase and induces apoptosis in human oral carcinoma (KB) cells possibly via oxidative DNA damage. Biomed Pharmacother 92:661–671

    Article  CAS  PubMed  Google Scholar 

  • Vishnu WK, Abeesh P, Guruvayoorappan C (2021) Pyrazole (1, 2-diazole) induce apoptosis in lymphoma cells by targeting BCL-2 and BCL-XL genes and mitigate murine solid tumour development by regulating cyclin-D1 and Ki-67 expression. Toxicol Appl Pharmacol 418:115491

    Article  CAS  PubMed  Google Scholar 

  • Wei Y, Liang J, Zheng X, Pi C, Liu H, Yang H, Zou Y, Ye Y, Zhao L (2017) Lung-targeting drug delivery system of baicalin-loaded nanoliposomes: development, biodistribution in rabbits, and pharmacodynamics in nude mice bearing orthotopic human lung cancer. Int J Nanomed 12:251

    Article  CAS  Google Scholar 

  • Wu D, Gao Y, Qi Y, Chen L, Ma Y, Li Y (2014) Peptide-based cancer therapy: opportunity and challenge. Cancer Lett 351(1):13–22

    Article  CAS  PubMed  Google Scholar 

  • Yu SM, Hu DH, Zhang JJ (2015) Umbelliferone exhibits anticancer activity via the induction of apoptosis and cell cycle arrest in HepG2 hepatocellular carcinoma cells. Mol Med Rep 12(3):3869–3873

    Article  CAS  PubMed  Google Scholar 

  • Zocchi MR, Tosetti F, Benelli R, Poggi AJC (2020) Cancer nanomedicine special issue review anticancer drug delivery with nanoparticles: extracellular vesicles or synthetic nanobeads as therapeutic tools for conventional treatment or immunotherapy. Cancers 12(7):1886

  • Zucker D, Andriyanov AV, Steiner A, Raviv U, Barenholz Y (2012) Characterization of PEGylated nanoliposomes co-remotely loaded with topotecan and vincristine: relating structure and pharmacokinetics to therapeutic efficacy. J Control Release 160(2):281–289

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Kerala Biotechnology Commission, Kerala State Council for Science Technology and Environment (KSCSTE) (no. 454/2020/KSCSTE)., and Department of Biotechnology (DBT) (DBT/JRF/BET-16/1/2016/Al/37-458) for providing financial assistance to the study. The authors thank Dr. S. Lakshmi, Head, Division of Cancer Research and Dr. Rekha A. Nair, Director, Regional Cancer Centre, for their valuable support.

Author information

Authors and Affiliations

  1. Laboratory of Immunopharmacology and Experimental Therapeutics, Division of Cancer Research, Regional Cancer Centre, Medical College Campus, Thiruvananthapuram, Kerala, 695 011, India

    Prathapan Abeesh & Chandrasekharan Guruvayoorappan

Authors
  1. Prathapan Abeesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chandrasekharan Guruvayoorappan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PA: investigation, methodology, analysis, writing—original draft, editing, visualization, funding acquisition. CG: conceptualization, review—editing, supervision, project administration, funding acquisition.

Corresponding author

Correspondence to Chandrasekharan Guruvayoorappan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest in the publication.

Ethical approval

Animal experiments were approved by the Institutional Animal Ethics Committee, Regional Cancer Centre (Kerala, India).

Informed consent

Not applicable.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abeesh, P., Guruvayoorappan, C. Umbelliferone loaded PEGylated liposomes: preparation, characterization and its mitigatory effects on Dalton’s ascites lymphoma development. 3 Biotech 13, 216 (2023). https://doi.org/10.1007/s13205-023-03615-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-023-03615-x

Keywords

Search

Navigation