PolyRad – Protection Against Free Radical Damage

Abstract The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel spa...

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Autores principales:	Hannah Kim, Yin Tse, Andrew Webb, Ethan Mudd, Muhammad Raisul Abedin, Melanie Mormile, Subhadeep Dutta, Kaushal Rege, Sutapa Barua
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/017b0ad86d104ad890fa2112a885c77c
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spelling	oai:doaj.org-article:017b0ad86d104ad890fa2112a885c77c2021-12-02T14:59:15ZPolyRad – Protection Against Free Radical Damage10.1038/s41598-020-65247-y2045-2322https://doaj.org/article/017b0ad86d104ad890fa2112a885c77c2020-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65247-yhttps://doaj.org/toc/2045-2322Abstract The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H2O2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H2O2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H2O2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dose-dependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration $$ \sim $$ ~ 0.01 $${mg}/{ml}$$ mg/ml ($$10\mu g/{ml}$$ 10μg/ml ). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications.Hannah KimYin TseAndrew WebbEthan MuddMuhammad Raisul AbedinMelanie MormileSubhadeep DuttaKaushal RegeSutapa BaruaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hannah Kim Yin Tse Andrew Webb Ethan Mudd Muhammad Raisul Abedin Melanie Mormile Subhadeep Dutta Kaushal Rege Sutapa Barua PolyRad – Protection Against Free Radical Damage
description	Abstract The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations. This work aims to develop a novel approach for the protection of space pharmaceutical drug molecules from the radiation-induced damage to help extend or at least preserve their structural integrity and potency. To achieve this, free radical scavenging antioxidant, Trolox was conjugated on the surface of poly-lactic-co-glycolic acid (PLGA) nanoparticles for the protection of a candidate drug, melatonin that is used as a sleep aid medication in International Space Station (ISS). Melatonin-PLGA-PLL-Trolox nanoparticle as named as PolyRad was synthesized employing single oil in water (o/w) emulsion solvent evaporation method. PolyRad is spherical in shape and has an average diameter of ~600 nm with a low polydispersity index of 0.2. PolyRad and free melatonin (control) were irradiated by UV light after being exposed to a strong oxidant, hydrogen peroxide (H2O2). Bare melatonin lost ~80% of the active structure of the drug following irradiation with UV light or treatment with H2O2. In contrast, PolyRad protected >80% of the active structure of melatonin. The ability of PolyRad to protect melatonin structure was also carried out using 0, 1, 5 and 10 Gy gamma radiation. Gamma irradiation showed >98% active structures of melatonin encapsulated in PolyRads. Drug release and effectiveness of melatonin using PolyRad were evaluated on human umbilical vein endothelial cells (HUVEC) in vitro. Non-irradiated PolyRad demonstrated maximum drug release of ~70% after 72 h, while UV-irradiated and H2O2-treated PolyRad showed a maximum drug release of ~85%. Cytotoxicity of melatonin was carried out using both live/dead and MTT assays. Melatonin, non-radiated PolyRad and irradiated PolyRad inhibited the viability of HUVEC in a dose-dependent manner. Cell viability of melatonin, PolyRad alone without melatonin (PolyRad carrier control), non-radiated PolyRad, and irradiated PolyRad were ~98, 87, 75 and 70%, respectively at a concentration $$ \sim $$ ~ 0.01 $${mg}/{ml}$$ mg/ml ($$10\mu g/{ml}$$ 10μg/ml ). Taken together, PolyRad nanoparticle provides an attractive formulation platform for preventing damage to pharmaceutical drugs in potential space mission applications.
format	article
author	Hannah Kim Yin Tse Andrew Webb Ethan Mudd Muhammad Raisul Abedin Melanie Mormile Subhadeep Dutta Kaushal Rege Sutapa Barua
author_facet	Hannah Kim Yin Tse Andrew Webb Ethan Mudd Muhammad Raisul Abedin Melanie Mormile Subhadeep Dutta Kaushal Rege Sutapa Barua
author_sort	Hannah Kim
title	PolyRad – Protection Against Free Radical Damage
title_short	PolyRad – Protection Against Free Radical Damage
title_full	PolyRad – Protection Against Free Radical Damage
title_fullStr	PolyRad – Protection Against Free Radical Damage
title_full_unstemmed	PolyRad – Protection Against Free Radical Damage
title_sort	polyrad – protection against free radical damage
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/017b0ad86d104ad890fa2112a885c77c
work_keys_str_mv	AT hannahkim polyradprotectionagainstfreeradicaldamage AT yintse polyradprotectionagainstfreeradicaldamage AT andrewwebb polyradprotectionagainstfreeradicaldamage AT ethanmudd polyradprotectionagainstfreeradicaldamage AT muhammadraisulabedin polyradprotectionagainstfreeradicaldamage AT melaniemormile polyradprotectionagainstfreeradicaldamage AT subhadeepdutta polyradprotectionagainstfreeradicaldamage AT kaushalrege polyradprotectionagainstfreeradicaldamage AT sutapabarua polyradprotectionagainstfreeradicaldamage
_version_	1718389178774847488

PolyRad – Protection Against Free Radical Damage

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