Development of a stable single-vial liposomal formulation for vincristine

Wenxue Mao,1 Fan Wu,2 Robert J Lee,3 Weigen Lu,4 Jianxin Wang11Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, People’s Republic of China; 2College of Medicine, Des Moines University,...

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Autores principales:	Mao W, Wu F, Lee RJ, Lu W, Wang J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	vincristine sulfate liposome TEA-SOS storage stability and anti-tumor efficacy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8564c3cf87b842dda4c94f2786156426
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spelling	oai:doaj.org-article:8564c3cf87b842dda4c94f27861564262021-12-02T03:01:50ZDevelopment of a stable single-vial liposomal formulation for vincristine1178-2013https://doaj.org/article/8564c3cf87b842dda4c94f27861564262019-06-01T00:00:00Zhttps://www.dovepress.com/development-of-a-stable-single-vial-liposomal-formulation-for-vincrist-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wenxue Mao,1 Fan Wu,2 Robert J Lee,3 Weigen Lu,4 Jianxin Wang11Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, People’s Republic of China; 2College of Medicine, Des Moines University, Des Moines, IA 50312, USA; 3Division of Pharmaceutics and Pharmaceutical Chemistry, Ohio State University, Columbus, OH 43210, USA; 4China State Institute of Pharmaceutical Industry, Shanghai 201203, People’s Republic of ChinaBackground: Vincristine is a potent therapeutic agent with well-defined activity against hematologic malignancies and solid tumors. It is a cell-cycle specific drug with concentration and exposure duration dependent activity. When used by liposomal delivery, it exhibits enhanced anti-tumor activity. However, vincristine liposome formulation in the clinic is supplied as a 3-vial-kit due to lacking sufficient stability. So it has to be prepared in situ prior to use through a multi-step process.Purpose: The purpose here is to develop a more stable and ready-to-use liposomal formulation for vincritstine in one vial.Patients and methods: A series of preparations were investigated based on sphingomyelin/cholesterol/PEG2000-DSPE lipid composition, with different drug/lipid (D/L) ratios (1/10, 1/5, 1/2), using an active sucrose octasulfate triethylamine salt gradient loading method. In this work, compared to generic vincristine sulfate liposome injection (GVM), the stability both in vivo and in vitro and efficacy in vivo of novel vincristine liposomes were investigated.Results: It was shown that the degradation of vincristine during 2–8°C storage was significantly decreased from 8.2% in 1 month (GVM) to 2.9% in 12 months (D/L ratio 1/5). The half-time for sphingomyelin/cholesterol/PEG2000-DSPE liposomes in vivo could be adjusted from 17.4 h (D/L ratio 1/10) to 22.7 h (D/L ratio 1/2) in rats, while the half-time for GVM was only 11.1 h. The increase in drug retention contributed to the lower in vivo toxicity. The antitumor efficacy was evaluated using a human melanoma tumor model and showed remarkable improvement compared to GVM.Conclusion: The study demonstrates that the new formulation with the drug/lipid ratio of 1/5 owns a higher encapsulation efficiency, better stability, lower toxicity and superior antitumor efficacy, which is screened out for further development.Keywords: vincristine sulfate, liposome, TEA-SOS, storage stability, and anti-tumor efficacyMao WWu FLee RJLu WWang JDove Medical Pressarticlevincristine sulfateliposomeTEA-SOSstorage stabilityand anti-tumor efficacyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 4461-4474 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	vincristine sulfate liposome TEA-SOS storage stability and anti-tumor efficacy Medicine (General) R5-920
spellingShingle	vincristine sulfate liposome TEA-SOS storage stability and anti-tumor efficacy Medicine (General) R5-920 Mao W Wu F Lee RJ Lu W Wang J Development of a stable single-vial liposomal formulation for vincristine
description	Wenxue Mao,1 Fan Wu,2 Robert J Lee,3 Weigen Lu,4 Jianxin Wang11Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, People’s Republic of China; 2College of Medicine, Des Moines University, Des Moines, IA 50312, USA; 3Division of Pharmaceutics and Pharmaceutical Chemistry, Ohio State University, Columbus, OH 43210, USA; 4China State Institute of Pharmaceutical Industry, Shanghai 201203, People’s Republic of ChinaBackground: Vincristine is a potent therapeutic agent with well-defined activity against hematologic malignancies and solid tumors. It is a cell-cycle specific drug with concentration and exposure duration dependent activity. When used by liposomal delivery, it exhibits enhanced anti-tumor activity. However, vincristine liposome formulation in the clinic is supplied as a 3-vial-kit due to lacking sufficient stability. So it has to be prepared in situ prior to use through a multi-step process.Purpose: The purpose here is to develop a more stable and ready-to-use liposomal formulation for vincritstine in one vial.Patients and methods: A series of preparations were investigated based on sphingomyelin/cholesterol/PEG2000-DSPE lipid composition, with different drug/lipid (D/L) ratios (1/10, 1/5, 1/2), using an active sucrose octasulfate triethylamine salt gradient loading method. In this work, compared to generic vincristine sulfate liposome injection (GVM), the stability both in vivo and in vitro and efficacy in vivo of novel vincristine liposomes were investigated.Results: It was shown that the degradation of vincristine during 2–8°C storage was significantly decreased from 8.2% in 1 month (GVM) to 2.9% in 12 months (D/L ratio 1/5). The half-time for sphingomyelin/cholesterol/PEG2000-DSPE liposomes in vivo could be adjusted from 17.4 h (D/L ratio 1/10) to 22.7 h (D/L ratio 1/2) in rats, while the half-time for GVM was only 11.1 h. The increase in drug retention contributed to the lower in vivo toxicity. The antitumor efficacy was evaluated using a human melanoma tumor model and showed remarkable improvement compared to GVM.Conclusion: The study demonstrates that the new formulation with the drug/lipid ratio of 1/5 owns a higher encapsulation efficiency, better stability, lower toxicity and superior antitumor efficacy, which is screened out for further development.Keywords: vincristine sulfate, liposome, TEA-SOS, storage stability, and anti-tumor efficacy
format	article
author	Mao W Wu F Lee RJ Lu W Wang J
author_facet	Mao W Wu F Lee RJ Lu W Wang J
author_sort	Mao W
title	Development of a stable single-vial liposomal formulation for vincristine
title_short	Development of a stable single-vial liposomal formulation for vincristine
title_full	Development of a stable single-vial liposomal formulation for vincristine
title_fullStr	Development of a stable single-vial liposomal formulation for vincristine
title_full_unstemmed	Development of a stable single-vial liposomal formulation for vincristine
title_sort	development of a stable single-vial liposomal formulation for vincristine
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8564c3cf87b842dda4c94f2786156426
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Development of a stable single-vial liposomal formulation for vincristine

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