酶替代疗法
法布里病
溶酶体贮存障碍
溶酶体贮存病
PLGA公司
体内
血脑屏障
酶
药理学
粘多糖病Ⅱ型
白蛋白
新生儿筛查
医学
化学
生物化学
体外
生物
中枢神经系统
内科学
疾病
生物技术
作者
Marika Salvalaio,Laura Rigon,Daniela Belletti,Francesca D’Avanzo,Francesca Pederzoli,Barbara Ruozi,Oriano Marin,Maria Angela Vandelli,Flavio Forni,Maurizio Scarpa,Rosella Tomanin,Giovanni Tosi
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2016-05-26
卷期号:11 (5): e0156452-e0156452
被引量:73
标识
DOI:10.1371/journal.pone.0156452
摘要
Lysosomal Storage Disorders (LSDs) are a group of metabolic syndromes, each one due to the deficit of one lysosomal enzyme. Many LSDs affect most of the organ systems and overall about 75% of the patients present neurological impairment. Enzyme Replacement Therapy, although determining some systemic clinical improvements, is ineffective on the CNS disease, due to enzymes' inability to cross the blood-brain barrier (BBB). With the aim to deliver the therapeutic enzymes across the BBB, we here assayed biodegradable and biocompatible PLGA-nanoparticles (NPs) in two murine models for LSDs, Mucopolysaccharidosis type I and II (MPS I and MPS II). PLGA-NPs were modified with a 7-aminoacid glycopeptide (g7), yet demonstrated to be able to deliver low molecular weight (MW) molecules across the BBB in rodents. We specifically investigated, for the first time, the g7-NPs ability to transfer a model drug (FITC-albumin) with a high MW, comparable to the enzymes to be delivered for LSDs brain therapy. In vivo experiments, conducted on wild-type mice and knockout mouse models for MPS I and II, also included a whole series of control injections to obtain a broad preliminary view of the procedure efficiency. Results clearly showed efficient BBB crossing of albumin in all injected mice, underlying the ability of NPs to deliver high MW molecules to the brain. These results encourage successful experiments with enzyme-loaded g7-NPs to deliver sufficient amounts of the drug to the brain district on LSDs, where exerting a corrective effect on the pathological phenotype.
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