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微流控介导的磷脂自组装用于生物分子的递送。

Microfluidic-mediated self-assembly of phospholipids for the delivery of biologic molecules.

机构信息

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

Immunocore, 92 Park Dr, Milton, Abingdon OX14 4RY, UK.

出版信息

Int J Pharm. 2022 Jan 5;611:121347. doi: 10.1016/j.ijpharm.2021.121347. Epub 2021 Dec 7.

Abstract

The encapsulation of biologic molecules using a microfluidic platform is a procedure that has been understudied but shows great promise from initial reported studies. The study focusses upon the encapsulation of bovine serum albumin (BSA) under various parameters and using multiple phospholipids to identify optimal conditions for the manufacturing of protein loaded lipid nanoparticles. Additionally, encapsulation of the enzyme trypsin (TRP) has been investigated to show the eligibility of the system to other biological medications. All liposomes were subject to rigorous physicochemical characterisation, including differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR), to document the successful synthesis of the liposomes. Drug-loaded liposome stability was investigated over a 28-day period at 5 °C and 37 °C, which showed encouraging results for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at all concentrations of BSA used. The sample containing 1 mg/ml BSA grew by only 10% over the study, which considering liposomes should be affected highly by biologic adsorption, shows great promise for the formulations. Encapsulation and in vitro release studies showed improved loading capacity for BSA compared to conventional methods, whilst maintaining a concise controlled release of the active pharmaceutical ingredient (API).

摘要

使用微流控平台对生物分子进行包封是一个研究较少但从最初的报道研究中显示出巨大前景的过程。该研究侧重于在各种参数下包封牛血清白蛋白(BSA),并使用多种磷脂来确定制造载有蛋白质的脂质纳米粒的最佳条件。此外,还研究了酶胰蛋白酶(TRP)的包封,以证明该系统适用于其他生物药物。所有脂质体都经过严格的物理化学特性分析,包括差示扫描量热法(DSC)和傅里叶变换红外光谱(FTIR),以证明脂质体的成功合成。在 5°C 和 37°C 下,对载药脂质体的稳定性进行了为期 28 天的研究,结果令人鼓舞,对于所有使用的 BSA 浓度的 1,2-二棕榈酰-sn-甘油-3-磷酸胆碱(DPPC)均如此。在研究过程中,含有 1mg/ml BSA 的样品仅增加了 10%,考虑到脂质体应该受到生物吸附的高度影响,这为配方提供了很大的希望。包封和体外释放研究表明,与传统方法相比,BSA 的载药量得到了提高,同时保持了活性药物成分(API)的简洁控制释放。

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