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基于聚琥珀酰亚胺-油胺的载蛋白纳米颗粒的制备用于蛋白质的持续释放:一种两步纳米沉淀法。

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method.

作者信息

Chen Xiangxun, Moonshi Shehzahdi S, Nguyen Nam-Trung, Ta Hang Thu

机构信息

School of Environment and Science, Griffith University, Brisbane, Queensland 4111, Australia.

Queensland Micro- and Nanotechnology Centre, Griffith University, Brisbane, Queensland 4111, Australia.

出版信息

Nanotechnology. 2023 Nov 15;35(5). doi: 10.1088/1361-6528/ad0592.

Abstract

Currently, the treatment for acute disease encompasses the use of various biological drugs (BDs). However, the utilisation of BDs is limited due to their rapid clearance and non-specific accumulation in unwanted sites, resulting in a lack of therapeutic efficacy together with adverse effects. While nanoparticles are considered good candidates to resolve this problem, some available polymeric carriers for BDs were mainly designed for long-term sustained release. Thus, there is a need to explore new polymeric carriers for the acute disease phase that requires sustained release of BDs over a short period, for example for thrombolysis and infection. Poly(succinimide)-oleylamine (PSI-OA), a biocompatible polymer with a tuneable dissolution profile, represents a promising strategy for loading BDs for sustained release within a 48-h period. In this work, we developed a two-step nanoprecipitation method to load the model protein (e.g. bovine serum albumin and lipase) on PSI-OA. The characteristics of the nanoparticles were assessed based on various loading parameters, such as concentration, stirring rate, flow rate, volume ratio, dissolution and release of the protein. The optimised NPs displayed a size within 200 nm that is suitable for vasculature delivery to the target sites. These findings suggest that PSI-OA can be employed as a carrier for BDs for applications that require sustained release over a short period.

摘要

目前,急性疾病的治疗包括使用各种生物药物(BDs)。然而,BDs的应用受到限制,因为它们会迅速清除且在非靶位点非特异性积累,导致缺乏治疗效果并产生不良反应。虽然纳米颗粒被认为是解决这一问题的理想选择,但一些现有的用于BDs的聚合物载体主要是为长期缓释而设计的。因此,有必要探索用于急性疾病阶段的新型聚合物载体,该阶段需要在短时间内实现BDs的持续释放,例如用于溶栓和感染治疗。聚琥珀酰亚胺 - 油胺(PSI - OA)是一种具有可调节溶解特性的生物相容性聚合物,是在48小时内实现BDs持续释放的一种有前景的策略。在这项工作中,我们开发了一种两步纳米沉淀法,将模型蛋白(如牛血清白蛋白和脂肪酶)负载到PSI - OA上。基于各种负载参数,如浓度、搅拌速率、流速、体积比、蛋白的溶解和释放等,对纳米颗粒的特性进行了评估。优化后的纳米颗粒尺寸在200nm以内,适合通过脉管系统输送到靶位点。这些发现表明,PSI - OA可作为BDs的载体,用于需要在短时间内持续释放的应用。

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