Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin

Enrico Gallo,1 Carlo Diaferia,2 Elisabetta Rosa,2 Giovanni Smaldone,1 Giancarlo Morelli,2 Antonella Accardo2 1IRCCS SDN, Naples, 80143, Italy; 2Department of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Naples, 80134, ItalyCorre...

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Autores principales:	Gallo E, Diaferia C, Rosa E, Smaldone G, Morelli G, Accardo A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hydrogels nanogels drug delivery peptide materials doxorubicin in vitro assays. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/53e9f6e0d93a455fbfb5c0be644e2446
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spelling	oai:doaj.org-article:53e9f6e0d93a455fbfb5c0be644e24462021-12-02T14:18:48ZPeptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin1178-2013https://doaj.org/article/53e9f6e0d93a455fbfb5c0be644e24462021-03-01T00:00:00Zhttps://www.dovepress.com/peptide-based-hydrogels-and-nanogels-for-delivery-of-doxorubicin-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Enrico Gallo,1 Carlo Diaferia,2 Elisabetta Rosa,2 Giovanni Smaldone,1 Giancarlo Morelli,2 Antonella Accardo2 1IRCCS SDN, Naples, 80143, Italy; 2Department of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Naples, 80134, ItalyCorrespondence: Antonella AccardoDepartment of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Via Mezzocannone 16, Naples, 80134, ItalyTel +39 0812532045Fax +39 0812536642Email antonella.accardo@unina.itIntroduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil.Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the “solvent-switch” method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN® 60 and SPAN® 60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays.Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20– 40 min) and the drug release (16– 28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20– 40%) after 72 h. Empty HGs and NGs show a high cell viability (> 95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49– 57%) and 72 h (7– 25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug.Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.Keywords: hydrogels, nanogels, drug delivery, peptide materials, doxorubicin, in vitro assaysGallo EDiaferia CRosa ESmaldone GMorelli GAccardo ADove Medical Pressarticlehydrogelsnanogelsdrug deliverypeptide materialsdoxorubicinin vitro assays.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 1617-1630 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydrogels nanogels drug delivery peptide materials doxorubicin in vitro assays. Medicine (General) R5-920
spellingShingle	hydrogels nanogels drug delivery peptide materials doxorubicin in vitro assays. Medicine (General) R5-920 Gallo E Diaferia C Rosa E Smaldone G Morelli G Accardo A Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
description	Enrico Gallo,1 Carlo Diaferia,2 Elisabetta Rosa,2 Giovanni Smaldone,1 Giancarlo Morelli,2 Antonella Accardo2 1IRCCS SDN, Naples, 80143, Italy; 2Department of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Naples, 80134, ItalyCorrespondence: Antonella AccardoDepartment of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Via Mezzocannone 16, Naples, 80134, ItalyTel +39 0812532045Fax +39 0812536642Email antonella.accardo@unina.itIntroduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil.Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the “solvent-switch” method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN® 60 and SPAN® 60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays.Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20– 40 min) and the drug release (16– 28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20– 40%) after 72 h. Empty HGs and NGs show a high cell viability (> 95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49– 57%) and 72 h (7– 25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug.Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.Keywords: hydrogels, nanogels, drug delivery, peptide materials, doxorubicin, in vitro assays
format	article
author	Gallo E Diaferia C Rosa E Smaldone G Morelli G Accardo A
author_facet	Gallo E Diaferia C Rosa E Smaldone G Morelli G Accardo A
author_sort	Gallo E
title	Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
title_short	Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
title_full	Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
title_fullStr	Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
title_full_unstemmed	Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin
title_sort	peptide-based hydrogels and nanogels for delivery of doxorubicin
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/53e9f6e0d93a455fbfb5c0be644e2446
work_keys_str_mv	AT galloe peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin AT diaferiac peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin AT rosae peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin AT smaldoneg peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin AT morellig peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin AT accardoa peptidebasedhydrogelsandnanogelsfordeliveryofdoxorubicin
_version_	1718391605512110080

Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin

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