4.7 Article

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

期刊

ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 16, 期 5, 页码 633-642

出版社

SHENYANG PHARMACEUTICAL UNIV
DOI: 10.1016/j.ajps.2021.07.003

关键词

Arsenic trioxide; All trans retinoic acid; Phospholipid phase separation gel; Sustained-release; Bioavailability; Compliance

资金

  1. Science and Technology Commission of Shanghai Municipality [20S11902600]

向作者/读者索取更多资源

ATO + ATRA-PPSG is a novel drug delivery system for the treatment of acute promyelocytic leukemia, which can slow release drugs, reduce side effects, and prolong survival time.
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 t(1/2) 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. (C) 2021 Shenyang Pharmaceutical University. Published by Elsevier B.V.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据