Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice

Kalaimathi Murugesan,1 Padmapriya Srinivasan,1,* Raghunandan Mahadeva,1,* Chhitar M Gupta,1 Wahajul Haq2 1Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, India; 2Central Drug Research Institute (CDRI), Medicinal and Process Chemistry Division, Lucknow, India*These authors co...

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Autores principales:	Murugesan K, Srinivasan P, Mahadeva R, Gupta CM, Haq W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	palmitoyl-tuftsin antitumor doxorubicin curcumin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a56e0c70be574309ae9aa6fb17273532
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spelling	oai:doaj.org-article:a56e0c70be574309ae9aa6fb172735322021-12-02T16:01:14ZTuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice1178-2013https://doaj.org/article/a56e0c70be574309ae9aa6fb172735322020-12-01T00:00:00Zhttps://www.dovepress.com/tuftsin-bearing-liposomes-co-encapsulated-with-doxorubicin-and-curcumi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Kalaimathi Murugesan,1 Padmapriya Srinivasan,1,* Raghunandan Mahadeva,1,* Chhitar M Gupta,1 Wahajul Haq2 1Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, India; 2Central Drug Research Institute (CDRI), Medicinal and Process Chemistry Division, Lucknow, India*These authors contributed equally to this workCorrespondence: Kalaimathi MurugesanInstitute of Bioinformatics and Applied Biotechnology (IBAB), Biotech Park, Electronic City Phase I, Bangalore 560100, IndiaTel +919585986415Email mathi.biotech@gmail.comBackground: Targeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH2)2-NH-COC15H31, P.Tuft) to enable its grafting within the liposome’s bilayer.Methods: The prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV–visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.Results: A significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).Conclusion: In conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.Keywords: palmitoyl-tuftsin, antitumor, doxorubicin, curcuminMurugesan KSrinivasan PMahadeva RGupta CMHaq WDove Medical Pressarticlepalmitoyl-tuftsinantitumordoxorubicincurcuminMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 10547-10559 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	palmitoyl-tuftsin antitumor doxorubicin curcumin Medicine (General) R5-920
spellingShingle	palmitoyl-tuftsin antitumor doxorubicin curcumin Medicine (General) R5-920 Murugesan K Srinivasan P Mahadeva R Gupta CM Haq W Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
description	Kalaimathi Murugesan,1 Padmapriya Srinivasan,1,* Raghunandan Mahadeva,1,* Chhitar M Gupta,1 Wahajul Haq2 1Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, India; 2Central Drug Research Institute (CDRI), Medicinal and Process Chemistry Division, Lucknow, India*These authors contributed equally to this workCorrespondence: Kalaimathi MurugesanInstitute of Bioinformatics and Applied Biotechnology (IBAB), Biotech Park, Electronic City Phase I, Bangalore 560100, IndiaTel +919585986415Email mathi.biotech@gmail.comBackground: Targeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH2)2-NH-COC15H31, P.Tuft) to enable its grafting within the liposome’s bilayer.Methods: The prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV–visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.Results: A significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).Conclusion: In conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.Keywords: palmitoyl-tuftsin, antitumor, doxorubicin, curcumin
format	article
author	Murugesan K Srinivasan P Mahadeva R Gupta CM Haq W
author_facet	Murugesan K Srinivasan P Mahadeva R Gupta CM Haq W
author_sort	Murugesan K
title	Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
title_short	Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
title_full	Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
title_fullStr	Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
title_full_unstemmed	Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
title_sort	tuftsin-bearing liposomes co-encapsulated with doxorubicin and curcumin efficiently inhibit eac tumor growth in mice
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/a56e0c70be574309ae9aa6fb17273532
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Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice

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