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系统改造与评价载酶壳聚糖纳米粒。

Systematic Modification and Evaluation of Enzyme-Loaded Chitosan Nanoparticles.

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.

出版信息

Int J Mol Sci. 2021 Jul 26;22(15):7987. doi: 10.3390/ijms22157987.

DOI:10.3390/ijms22157987
PMID:34360752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8348744/
Abstract

Polymeric-based nano drug delivery systems have been widely exploited to overcome protein instability during formulation. Presently, a diverse range of polymeric agents can be used, among which polysaccharides, such as chitosan (CS), hyaluronic acid (HA) and cyclodextrins (CDs), are included. Due to its unique biological and physicochemical properties, CS is one of the most used polysaccharides for development of protein delivery systems. However, CS has been described as potentially immunogenic. By envisaging a biosafe cytocompatible and haemocompatible profile, this paper reports the systematic development of a delivery system based on CS and derived with HA and CDs to nanoencapsulate the model human phenylalanine hydroxylase (hPAH) through ionotropic gelation with tripolyphosphate (TPP), while maintaining protein stability and enzyme activity. By merging the combined set of biopolymers, we were able to effectively entrap hPAH within CS nanoparticles with improvements in hPAH stability and the maintenance of functional activity, while simultaneously achieving strict control of the formulation process. Detailed characterization of the developed nanoparticulate systems showed that the lead formulations were internalized by hepatocytes (HepG2 cell line), did not reveal cell toxicity and presented a safe haemocompatible profile.

摘要

基于聚合物的纳米药物递送系统已被广泛用于克服制剂过程中蛋白质的不稳定性。目前，可以使用多种聚合物试剂，其中包括多糖，如壳聚糖（CS）、透明质酸（HA）和环糊精（CDs）。由于其独特的生物学和物理化学性质，CS 是开发蛋白质递送系统最常用的多糖之一。然而，CS 已被描述为具有潜在的免疫原性。为了设想一种生物安全、细胞相容和血液相容的特性，本文通过与三聚磷酸（TPP）的离子凝胶作用，系统地开发了一种基于 CS 并衍生出 HA 和 CDs 的递送系统，以纳米封装模型人苯丙氨酸羟化酶（hPAH），同时保持蛋白质的稳定性和酶活性。通过合并这组生物聚合物，我们能够有效地将 hPAH 包埋在 CS 纳米颗粒内，提高 hPAH 的稳定性并保持功能活性，同时严格控制制剂过程。对所开发的纳米颗粒系统的详细表征表明，主导配方被肝细胞（HepG2 细胞系）内化，没有显示出细胞毒性，并呈现出安全的血液相容性特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/8f7271216689/ijms-22-07987-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/db46f35de6ad/ijms-22-07987-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/0e69b1e3701f/ijms-22-07987-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/308c98a19d9e/ijms-22-07987-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/28fb82833665/ijms-22-07987-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/9b2191d5fa55/ijms-22-07987-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/8f7271216689/ijms-22-07987-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/db46f35de6ad/ijms-22-07987-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/af95e6c69ce2/ijms-22-07987-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/0e69b1e3701f/ijms-22-07987-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/308c98a19d9e/ijms-22-07987-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/28fb82833665/ijms-22-07987-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/9b2191d5fa55/ijms-22-07987-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/800b/8348744/8f7271216689/ijms-22-07987-g009.jpg

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