Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics

Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX)...

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Autores principales:	Gunjan Jeswani, Lipika Chablani, Umesh Gupta, Rakesh K. Sahoo, Kartik T. Nakhate, Ajazuddin
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Paclitaxel Nanoparticle(s) Eudragit RLPO Eudragit RSPO PLGA Design of experiments (DOE) Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/84fc823fdddf4f0ea1be7d3248762892
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spelling	oai:doaj.org-article:84fc823fdddf4f0ea1be7d32487628922021-11-14T04:29:14ZDevelopment and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics0753-332210.1016/j.biopha.2021.112286https://doaj.org/article/84fc823fdddf4f0ea1be7d32487628922021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010702https://doaj.org/toc/0753-3322Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77–214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55–163,071.15 h*ng/mL), longer half-lives (5.80–6.35 h) and extended mean residence times (6.05–8.54 h) in comparison to PTX solution (p < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects.Gunjan JeswaniLipika ChablaniUmesh GuptaRakesh K. SahooKartik T. Nakhate AjazuddinElsevierarticlePaclitaxelNanoparticle(s)Eudragit RLPOEudragit RSPOPLGADesign of experiments (DOE)Therapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112286- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Paclitaxel Nanoparticle(s) Eudragit RLPO Eudragit RSPO PLGA Design of experiments (DOE) Therapeutics. Pharmacology RM1-950
spellingShingle	Paclitaxel Nanoparticle(s) Eudragit RLPO Eudragit RSPO PLGA Design of experiments (DOE) Therapeutics. Pharmacology RM1-950 Gunjan Jeswani Lipika Chablani Umesh Gupta Rakesh K. Sahoo Kartik T. Nakhate Ajazuddin Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
description	Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77–214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55–163,071.15 h*ng/mL), longer half-lives (5.80–6.35 h) and extended mean residence times (6.05–8.54 h) in comparison to PTX solution (p < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects.
format	article
author	Gunjan Jeswani Lipika Chablani Umesh Gupta Rakesh K. Sahoo Kartik T. Nakhate Ajazuddin
author_facet	Gunjan Jeswani Lipika Chablani Umesh Gupta Rakesh K. Sahoo Kartik T. Nakhate Ajazuddin
author_sort	Gunjan Jeswani
title	Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
title_short	Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
title_full	Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
title_fullStr	Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
title_full_unstemmed	Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics
title_sort	development and optimization of paclitaxel loaded eudragit/plga nanoparticles by simplex lattice mixture design: exploration of improved hemocompatibility and in vivo kinetics
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/84fc823fdddf4f0ea1be7d3248762892
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Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics

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