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利用可生物降解纳米载体实现亲水性药物的形态依赖性pH响应释放。

Morphology-dependent pH-responsive release of hydrophilic payloads using biodegradable nanocarriers.

作者信息

Pramanik Sumit Kumar, Seneca Senne, Peters Martijn, D'Olieslaeger Lien, Reekmans Gunter, Vanderzande Dirk, Adriaensens Peter, Ethirajan Anitha

机构信息

Institute for Materials Research (IMO), Hasselt University Wetenschapspark 1 and Agoralaan D, 3590 Diepenbeek Belgium

IMEC, Associated Lab IMOMEC Wetenschapspark 1, 3590 Diepenbeek Belgium.

出版信息

RSC Adv. 2018 Oct 31;8(64):36869-36878. doi: 10.1039/c8ra07066k. eCollection 2018 Oct 26.

DOI:10.1039/c8ra07066k
PMID:35558930
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9088891/
Abstract

The development of functional nanocarriers with stimuli-responsive properties has advanced tremendously to serve biomedical applications such as drug delivery and regenerative medicine. However, the development of biodegradable nanocarriers that can be loaded with hydrophilic compounds and ensure its controlled release in response to changes in the surrounding environment still remains very challenging. Herein, we achieved such demands the preparation of aqueous core nanocapsules using a base-catalyzed interfacial reaction employing a diisocyanate monomer and functional monomers/polymers containing thiol and hydroxyl functionalities at the droplet interface. pH-responsive poly(thiourethane-urethane) nanocarriers with ester linkages were synthesized by incorporating polycaprolactone diol, which is susceptible to hydrolytic degradation ester linkages, as a functional monomer in the reaction formulation. We could demonstrate that by systematically varying the number of biodegradable segments, the morphology of the nanocarriers can be tuned without imparting the efficient encapsulation of hydrophilic payload (>85% encapsulation efficiency) and its transfer from organic to aqueous phase. The developed nanocarriers allow for a fast release of hydrophilic payload that depends on pH, the number of biodegradable segments and nanocarrier morphology. Succinctly put, this study provides important information to develop pH-responsive nanocarriers with tunable morphology, using interfacial reactions in the inverse miniemulsion process, by controlling the number of degradable segments to adjust the release profile depending on the type of application envisaged.

摘要

具有刺激响应特性的功能性纳米载体的发展已取得巨大进展,可用于药物递送和再生医学等生物医学应用。然而,开发能够负载亲水性化合物并确保其在周围环境变化时实现控释的可生物降解纳米载体仍然极具挑战性。在此,我们通过在液滴界面使用二异氰酸酯单体与含有硫醇和羟基官能团的功能性单体/聚合物进行碱催化界面反应来制备水性核纳米胶囊,从而满足了此类需求。通过在反应配方中引入易受酯键水解降解影响的聚己内酯二醇作为功能性单体,合成了具有酯键的pH响应性聚(硫脲 - 聚氨酯)纳米载体。我们能够证明,通过系统地改变可生物降解链段的数量,可以调节纳米载体的形态,同时不影响亲水性有效载荷的高效包封(包封效率>85%)及其从有机相到水相的转移。所开发的纳米载体能够实现亲水性有效载荷的快速释放,其释放取决于pH值、可生物降解链段的数量和纳米载体的形态。简而言之,本研究提供了重要信息,即通过在反相微乳液过程中利用界面反应,通过控制可降解链段的数量来根据设想的应用类型调整释放曲线,从而开发具有可调形态的pH响应性纳米载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/ad77cd6232a5/c8ra07066k-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/37b4c9a4e698/c8ra07066k-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/ab2853abb736/c8ra07066k-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/231b16025a5b/c8ra07066k-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/97abacc833bd/c8ra07066k-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/ad77cd6232a5/c8ra07066k-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/37b4c9a4e698/c8ra07066k-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/ab2853abb736/c8ra07066k-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/231b16025a5b/c8ra07066k-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/97abacc833bd/c8ra07066k-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d13/9088891/ad77cd6232a5/c8ra07066k-f4.jpg

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