Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery

Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institu...

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Autores principales:	Fang YP, Wu PC, Huang YB, Tzeng CC, Chen YL, Hung YH, Tsai MJ, Tsai YH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1d0cdf4134a94db59d185c500000d3ff
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spelling	oai:doaj.org-article:1d0cdf4134a94db59d185c500000d3ff2021-12-02T07:28:31ZModification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery1176-91141178-2013https://doaj.org/article/1d0cdf4134a94db59d185c500000d3ff2012-09-01T00:00:00Zhttp://www.dovepress.com/modification-of-polyethylene-glycol-onto-solid-lipid-nanoparticles-enc-a11017https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 6School of Medicine, Medical College, China Medical University, Taichung, TaiwanBackground: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.Aims: To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%&ndash;64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P &lt; 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 &plusmn; 0.046 hours) when compared with the PK-L4 solution (0.078 &plusmn; 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine.Conclusion: Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.Keywords: 3-chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline, SLNs, solubility, cytotoxicity, biodistributionFang YPWu PCHuang YBTzeng CCChen YLHung YHTsai MJTsai YHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4995-5005 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Fang YP Wu PC Huang YB Tzeng CC Chen YL Hung YH Tsai MJ Tsai YH Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
description	Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 6School of Medicine, Medical College, China Medical University, Taichung, TaiwanBackground: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.Aims: To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%&ndash;64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P &lt; 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 &plusmn; 0.046 hours) when compared with the PK-L4 solution (0.078 &plusmn; 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine.Conclusion: Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.Keywords: 3-chloro-4-[(4-methoxyphenyl)amino]furo[2,3-b]quinoline, SLNs, solubility, cytotoxicity, biodistribution
format	article
author	Fang YP Wu PC Huang YB Tzeng CC Chen YL Hung YH Tsai MJ Tsai YH
author_facet	Fang YP Wu PC Huang YB Tzeng CC Chen YL Hung YH Tsai MJ Tsai YH
author_sort	Fang YP
title	Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
title_short	Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
title_full	Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
title_fullStr	Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
title_full_unstemmed	Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery
title_sort	modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (pk-l4) to enhance solubility for injection delivery
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/1d0cdf4134a94db59d185c500000d3ff
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Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4) to enhance solubility for injection delivery

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