Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1-7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers.
Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1-7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers.
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DOI：
10.3390/pharmaceutics13081278
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发表时间：
2021-08-17
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：
Alabsi W;Acosta MF;Al-Obeidi FA;Hay M;Polt R;Mansour HM
肽激素血管紧张素（1-7），Ang（1-7）或（asp - arg - val - tir - ile - his - pro）是肾素-血管紧张素系统（RAS）的重要组成部分，是Mas受体的中枢激动剂。中枢神经系统中该受体的激活刺激各种生物活性，使Ang (1-7)/MAS轴成为治疗许多疾病的新治疗方法。相关的O键糖肽asp - arg - val - tir - ile - hiss - ser -(O-β- d - glc)-amide （PNA5）是天然肽激素Ang的生物修饰（1-7），在体内表现出更高的稳定性和更高的脑渗透水平。我们已经合成了天然的Ang（1-7）肽和糖肽PNA5，并将它们配制成可吸入的干粉用于靶向呼吸输送。固相肽合成（SPPS）成功合成了Ang（1-7）和PNA5。通过实验和计算方法测量了生料Ang（1-7）和生料PNA5的溶解度和亲脂性，证实了肽和糖肽都具有高水溶性和两亲性。采用先进的有机溶液喷雾干燥技术对颗粒进行工程化处理，制备多肽和糖肽的喷雾干粉，以及与非还原糖和药用辅料海藻糖的共喷雾干粉（co-SD）。对天然肽、糖肽、SD和共SD粉末进行了全面表征，并表现出明显的玻璃化转变（Tg），与Tgs形成的无定形玻璃态相一致，可在体内使用。均匀颗粒在纳米尺度范围内表现出较小的尺寸和较低的固相残余含水量。在人体DPI装置上证明了良好的气溶胶分散性能。体外人细胞活力实验表明，Ang（1-7）和PNA5对不同的人呼吸细胞和脑细胞具有生物相容性和安全性。
The peptide hormone Angiotensin (1—7), Ang (1—7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin–angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1—7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1—7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1—7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1—7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1—7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (Tg) consistent with the amorphous glassy state formation with Tgs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1—7) and PNA5 are biocompatible and safe for different human respiratory and brain cells.
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影响因子：
8
作者：
Duan, Jinghua;Vogt, Frederick G.;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.
血管紧张素 - （1-7）/MAS受体作为癌症引起的骨痛的抗伤害感受剂。
影响因子：
7.4
作者：
Forte BL;Slosky LM;Zhang H;Arnold MR;Staatz WD;Hay M;Largent-Milnes TM;Vanderah TW
通讯作者：
Vanderah TW
影响因子：
5.4
作者：
Eedara BB;Alabsi W;Encinas-Basurto D;Polt R;Ledford JG;Mansour HM
通讯作者：
Mansour HM
DOI：
10.1124/jpet.104.069393
发表时间：
2004-10-01
影响因子：
3.5
作者：
Elmagbari, NO;Egleton, RD;Bilsky, EJ
通讯作者：
Bilsky, EJ
影响因子：
3.1
作者：
Acosta, Maria F.;Muralidharan, Priya;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.