Glycosylated Ang-(1-7) MasR Agonist Peptide Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles and Microparticles in Cognitive Impairment: Design, Particle Preparation, Physicochemical Characterization, and In Vitro Release.
Glycosylated Ang-(1-7) MasR Agonist Peptide Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles and Microparticles in Cognitive Impairment: Design, Particle Preparation, Physicochemical Characterization, and In Vitro Release.
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DOI：
10.3390/pharmaceutics14030587
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发表时间：
2022-03-08
期刊：
影响因子：
5.4
通讯作者：
Mansour HM
中科院分区：
文献类型：
--
作者：
Encinas-Basurto D;Konhilas JP;Polt R;Hay M;Mansour HM
心力衰竭 (HF) 会导致老年人的大脑灌注减少，而大脑和全身炎症的增加会增加认知障碍和阿尔茨海默病 (AD) 的风险。与 Ang-(1-7) 天然肽相比，糖基化 Ang-(1-7) MasR 激动剂 (PNA5) 具有更高的生物利用度、稳定性和脑渗透性。尽管结果良好且具有众多潜在应用，但 PNA5 糖肽的临床应用因其半衰期短而受到限制，并且需要频繁注射以确保认知障碍得到充分治疗。因此，需要PNA5糖肽的缓释注射制剂来提高其生物利用度，保护肽免于降解，并提供长时间的持续药物释放以减少注射给药频率。合成中使用了两种类型的聚（D,L-乳酸-乙醇酸）（PLGA）来生产负载有 PNA5（酯和酸封端）的纳米粒子（约 0.769–0.35 µm）和微粒（约 3.7–2.4 µm）。进行了全面的物理化学表征，包括扫描电子显微镜、热分析、分子指纹光谱、粒径、载药量、包封效率和体外药物释放。数据显示，尽管颗粒大小存在差异，但使用 PLGA R503H 聚合物成功实现了 PNA5 的缓释，其高载药量 (% DL) 和高包封率 (% EE) 分别 >8% 和 >40%。当使用酯端 PLGA 时，NPs 的缓释效果较差，72 小时后，几乎 100% 的肽被释放。此外，还观察到较低的 % EE 和 % DL 值（分别为 10.8 和 3.4）。这是第一个系统、全面的研究，报告了 PNA5 在 PLGA 纳米颗粒和微粒中的成功设计、颗粒合成、理化表征和体外糖肽药物释放。
Heart failure (HF) causes decreased brain perfusion in older adults, and increased brain and systemic inflammation increases the risk of cognitive impairment and Alzheimer’s disease (AD). Glycosylated Ang-(1-7) MasR agonists (PNA5) has shown improved bioavailability, stability, and brain penetration compared to Ang-(1-7) native peptide. Despite promising results and numerous potential applications, clinical applications of PNA5 glycopeptide are limited by its short half-life, and frequent injections are required to ensure adequate treatment for cognitive impairment. Therefore, sustained-release injectable formulations of PNA5 glycopeptide are needed to improve its bioavailability, protect the peptide from degradation, and provide sustained drug release over a prolonged time to reduce injection administration frequency. Two types of poly(D,L-lactic-co-glycolic acid) (PLGA) were used in the synthesis to produce nanoparticles (≈0.769–0.35 µm) and microparticles (≈3.7–2.4 µm) loaded with PNA5 (ester and acid-end capped). Comprehensive physicochemical characterization including scanning electron microscopy, thermal analysis, molecular fingerprinting spectroscopy, particle sizing, drug loading, encapsulation efficiency, and in vitro drug release were conducted. The data shows that despite the differences in the size of the particles, sustained release of PNA5 was successfully achieved using PLGA R503H polymer with high drug loading (% DL) and high encapsulation efficiency (% EE) of >8% and >40%, respectively. While using the ester-end PLGA, NPs showed poor sustained release as after 72 h, nearly 100% of the peptide was released. Also, lower % EE and % DL values were observed (10.8 and 3.4, respectively). This is the first systematic and comprehensive study to report on the successful design, particle synthesis, physicochemical characterization, and in vitro glycopeptide drug release of PNA5 in PLGA nanoparticles and microparticles.
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影响因子：
11.1
作者：
Cermakova P;Eriksdotter M;Lund LH;Winblad B;Religa P;Religa D
通讯作者：
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影响因子：
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作者：
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DOI：
10.1124/jpet.118.254854
发表时间：
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影响因子：
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0.8
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影响因子：
2.8
作者：
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通讯作者：
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