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Pharmaceutica 2016 會議：用於蛋白質藥物輸送的負載殼聚醣奈米顆粒的吸入粉末 - Sonia Al-Qadi - Birzeit 大學

索尼婭·卡迪

抽象的

這項工作計畫透過微膠囊化策略製造可吸入的胰島素堆疊殼聚醣奈米顆粒（INS-CS NP）粉末，並研究它們在體內的吸入同化作用。為此，透過將胰島素（INS）融合到由多醣殼聚醣（CS）和交聯劑三聚磷酸鈉（TPP）組成的奈米顆粒元件（NP）中，利用離子凝膠形成INS-CS NP。不久之後，INS-CS 奈米顆粒的形態、尺寸、zeta 電位和堆積極限被描述出來。接下來，將 INS-CS NP 懸浮液與糖甘露醇（熱保護劑）共濺乾，製成可吸入粉末，形成微結構粉末，具有足夠的流線型特性，適合肺功能。透過在囓齒類動物氣管內組織後檢查血漿葡萄糖水平來評估 INS-CS NP 淋浴乾燥粉末的體內執行情況。噴霧乾燥的 INS-CS 奈米顆粒被有效地微膠囊化到甘露醇微球中，形成具有適合深刻肺部宣誓的流線型特性的粉末。 IN-CS NPs/甘露醇的重量比例正如噴霧乾燥製程邊界一樣影響所獲得的微球的性質。此外，在流體介質中重新配製噴霧乾燥的粉末後，奈米粒子得到了有效的回收。體內檢查發現，與對照組（包括 INS 堆疊的甘露醇微球、局部 INS 排列和 INS-CS NP 懸浮液）相比，微囊 INS-CS NP 引發了越來越明確且延遲的降血糖作用。一般來說，除了非侵入性組織的優點和乾燥定義的理想可靠性之外，與液體夥伴相比，可吸入的小規模/奈米顆粒框架可以保證恢復性大分子的肺部運輸，以實現基本或局部影響（例如，囊性纖維化、肺部惡性生長）。

Peptides and proteins have extraordinary potential as therapeutics. At present, the market for peptide and protein drugs is evaluated to be more prominent than US$40 billion/year, or 10% of the pharmaceutical market. This market is developing a lot quicker than that of little particles, and will make up a considerably bigger extent of the market later on. At present there are more than 100 endorsed peptide-put together therapeutics with respect to the market, with the lion's share being littler than 20 amino acids. Contrasted and the normal little particle medicates that right now make up most of the pharmaceutical market, peptides and proteins can be exceptionally specific as they have numerous purposes of contact with their objective. Expanded selectivity may likewise bring about diminished reactions and harmfulness. Peptides can be intended to focus on a wide scope of particles, giving them practically boundless prospects in fields, for example, oncology, immunology, irresistible sickness and endocrinology. These peptide and protein therapeutics have impediments also, for example, low bioavailability and metabolic risk. Oral bioavailability of peptides is restricted by debasement in the gastrointestinal (GI) tract just as their powerlessness to cross the epithelial hindrance. These therapeutics will in general have high MWs, low lipophilicity

and charged useful gatherings that hamper their assimilation. These attributes lead to the low bioavailability of most orally controlled peptides (<2%) and short half-lives (<30 min) Intravenous (iv.) or subcutaneous (sc.) conveyance of these therapeutics beats the issue of assimilation, yet different elements limit the bio-accessibility of peptide and protein

therapeutics including: foundational proteases; fast digestion; opsonization; conformational changes; separation of subunit proteins; non-covalent complexation with blood items; and

demolition of labile side-gatherings.

As oral conveyance improves quiet consistence, there is incredible enthusiasm for the advancement of frameworks that take into consideration the oral conveyance of peptide and protein therapeutics. This survey will sum up the obstructions to different noninvasive conveyance techniques with an attention on oral and transdermal conveyance. Moreover, current strategies to defeat these conveyance obstructions will be talked about. The last bit of this paper will cover plans intended to defeat the issues of remedial focusing on and fundamental solidness. Fast improvement in sub-atomic science and late headway in recombinant innovation

increment distinguishing proof and commercialization of potential protein drugs. Conventional types of organizations for the peptide and protein tranquilizes regularly depend

on their parenteral infusion, since the bioavailability of these helpful specialists is poor when controlled nonparenterally. Enormous endeavors by various agents on the planet have been put to improve protein details and thus, a couple of fruitful definitions have been created including supported discharge human development hormone. For a promising protein conveyance innovation, adequacy and wellbeing are the principal necessity to meet. In any case, these frameworks despite everything require intermittent infusion and increment the rate of patient consistence. The advancement of an oral measurement structure that improves the retention of peptide and particularly protein drugs is the most alluring definition yet probably the best test in the pharmaceutical field. The significant boundaries to creating oral plans for peptides and proteins are metabolic catalysts and impermeable mucosal tissues in the digestive tract. Moreover, concoction and conformational shakiness of protein drugs is certifiably not a little issue in protein pharmaceuticals. Customary pharmaceutical ways to deal with address these boundaries, which have been fruitful with conventional natural medication atoms, have not been successful for peptide and protein plans. All things considered, viable oral details for peptides and proteins will remain profoundly compound explicit. Various creative oral medication conveyance approaches have been as of late created, including the medication entanglement inside little vesicles or their section through the intestinal paracellular pathway. Chitosan nanoparticles (NPs) are generally read as vehicles for medication, protein, and quality conveyance. In any case, absence of adequate security, especially under physiological conditions, render chitosan NPs of restricted pharmaceutical utility. The point of this examination is to create stable chitosan NPs appropriate for medicate conveyance applications. Chitosan was first joined to phthalic or phenylsuccinic acids. Hence, polyphosphoric corrosive (PPA), hexametaphosphate (HMP), or tripolyphosphate (TPP) were utilized to accomplish pair ionotropic/covalently crosslinked chitosan NPs within the sight of 1-ethyl-3-(3-dimethylaminopropyl)- carbodiimide (EDC).

溫暖和紅外線特徵證實了磷酰胺鍵的發展，將殼聚醣與奈米顆粒網絡內的聚磷酸酯交聯劑結合在一起。 DLS 和 TEM 尺寸檢查顯示圓形奈米粒子，尺寸範圍為 120 至 350 nm。所生產的奈米顆粒在嚴苛的 pH、CaCl2 和 10% FBS 條件下表現出強烈的品質。有趣的是，DLS、NP 穩定性和紅外線數據表明 HMP 存在於 NP 核心內，而 TPP 和 PPA 主要充當 NP 表面交聯劑。使用亞甲藍(MB) 和阿黴素(DOX) 藥物模型進行的藥物裝載和釋放研究表明，與僅通過離子交聯或通過TPP 共價交聯生成的基於未改性殼聚醣的NP 相比，基於共價PPA 和HMP 的NP 具有更高的負載能力。與遊離阿黴素相比，負載阿黴素的奈米粒子對 MCF-7 細胞具有優異的細胞毒性特性。具體而言，與遊離 DOX 相比，負載 DOX 的殼聚醣-鄰苯二甲酸酯多磷酸交聯的 NP 表現出 10 倍的細胞毒性增強。使用 PPA 和 HMP 生產共價穩定的殼聚醣奈米顆粒是完全新穎的。

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索尼婭·卡迪 (Sonia Al-Qadi) 是巴勒斯坦比爾澤特大學的助理教授。她在西班牙聖地亞哥德孔波斯特拉大學獲得了製藥技術碩士和博士學位。先後在南丹麥大學物理、化學和藥學系、哥本哈根大學藥學系從事博士後研究。此後，她在約旦伊斯拉大學藥學院擔任助理教授。她的研究興趣集中在奈米藥物遞送系統、生物材料和藥物測試模型。她發表了許多出版物，並在不同的國際會議上以海報或口頭報告的形式展示了她的研究成果，此外還擔任一些國際期刊的審查者。