A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia

Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid...

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Autores principales:	Xiao Liu, Weiwei Yin, Andy Samuel Widjaya, Yueying Yang, Yunhu Liu, Yanyan Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Arsenic trioxide All trans retinoic acid Phospholipid phase separation gel Sustained-release Bioavailability Compliance Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/acfc2041133b4d6b940e4682b557c104
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spelling	oai:doaj.org-article:acfc2041133b4d6b940e4682b557c1042021-11-20T04:57:43ZA practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia1818-087610.1016/j.ajps.2021.07.003https://doaj.org/article/acfc2041133b4d6b940e4682b557c1042021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1818087621000581https://doaj.org/toc/1818-0876Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid syndrome, serious drug resistance and the short half-life in vivo which lead to frequent and large dose administration limit the application of ATRA. In addition, the preparations of arsenic are conventional injections and tablets in clinic, which has poor patients' compliance caused by frequent long-term administration and serious side effects. In order to overcome the above limitations, a phospholipid phase separation gel (PPSG) loaded with ATO and ATRA was developed. ATO+ATRA-PPSG (AAP), as a biodegradable sustained-release delivery system, was the first achievement of co-delivery of hydrophilic ATO and lipophilic ATRA with high drug loading which is the main problem in the application of nano preparation. The prepared PPSG displayed high safety and biocompatibility. The drug in PPSG was released slowly and continuously in vivo and in vitro for up to 10 d, which could reduce the side effects caused by the fluctuation of blood drug concentration and solve the problem of the long treatment cycle and frequent administration. In vivo pharmacokinetics depicted that PPSG could improve the bioavailability, decrease the peak concentration, and prolong the t1/2 of ATO and ATRA. Particularly, AAP significantly inhibited the tumor volume, extended the survival period of tumor-bearing mice, and promoted the differentiation of APL cells into normal cells. Therefore, ATO+ATRA-PPSG not only could co-load hydrophilic ATO and lipophilic ATRA according to the clinical dosage, but also possessed the sustained-release and long-acting treatment effect which was expected to reduce administration time and ameliorate compliance of patients. Thus, it had great potential for clinical transformation and application.Xiao LiuWeiwei YinAndy Samuel WidjayaYueying YangYunhu LiuYanyan JiangElsevierarticleArsenic trioxideAll trans retinoic acidPhospholipid phase separation gelSustained-releaseBioavailabilityComplianceTherapeutics. PharmacologyRM1-950ENAsian Journal of Pharmaceutical Sciences, Vol 16, Iss 5, Pp 633-642 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arsenic trioxide All trans retinoic acid Phospholipid phase separation gel Sustained-release Bioavailability Compliance Therapeutics. Pharmacology RM1-950
spellingShingle	Arsenic trioxide All trans retinoic acid Phospholipid phase separation gel Sustained-release Bioavailability Compliance Therapeutics. Pharmacology RM1-950 Xiao Liu Weiwei Yin Andy Samuel Widjaya Yueying Yang Yunhu Liu Yanyan Jiang A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
description	Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid syndrome, serious drug resistance and the short half-life in vivo which lead to frequent and large dose administration limit the application of ATRA. In addition, the preparations of arsenic are conventional injections and tablets in clinic, which has poor patients' compliance caused by frequent long-term administration and serious side effects. In order to overcome the above limitations, a phospholipid phase separation gel (PPSG) loaded with ATO and ATRA was developed. ATO+ATRA-PPSG (AAP), as a biodegradable sustained-release delivery system, was the first achievement of co-delivery of hydrophilic ATO and lipophilic ATRA with high drug loading which is the main problem in the application of nano preparation. The prepared PPSG displayed high safety and biocompatibility. The drug in PPSG was released slowly and continuously in vivo and in vitro for up to 10 d, which could reduce the side effects caused by the fluctuation of blood drug concentration and solve the problem of the long treatment cycle and frequent administration. In vivo pharmacokinetics depicted that PPSG could improve the bioavailability, decrease the peak concentration, and prolong the t1/2 of ATO and ATRA. Particularly, AAP significantly inhibited the tumor volume, extended the survival period of tumor-bearing mice, and promoted the differentiation of APL cells into normal cells. Therefore, ATO+ATRA-PPSG not only could co-load hydrophilic ATO and lipophilic ATRA according to the clinical dosage, but also possessed the sustained-release and long-acting treatment effect which was expected to reduce administration time and ameliorate compliance of patients. Thus, it had great potential for clinical transformation and application.
format	article
author	Xiao Liu Weiwei Yin Andy Samuel Widjaya Yueying Yang Yunhu Liu Yanyan Jiang
author_facet	Xiao Liu Weiwei Yin Andy Samuel Widjaya Yueying Yang Yunhu Liu Yanyan Jiang
author_sort	Xiao Liu
title	A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
title_short	A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
title_full	A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
title_fullStr	A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
title_full_unstemmed	A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
title_sort	practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/acfc2041133b4d6b940e4682b557c104
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A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia

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