本研究開發一套以海藻酸鈉（Sodium Alginate, SA）與ε-聚賴氨酸（ε-Polylysine, PL）靜電自組裝形成之奈米粒子（SAPL）系統，作為Diazoxide lithium salt（DZX-Li）之鼻腔藥物遞送載體，藉由經鼻給藥可避開血腦屏障限制，提升藥物進入中樞神經系統的效率，並進一步引入螢光標記分子 Rhodamine 6G hydrazide（R6G），以利後續於細胞或組織內部進行定位與追蹤。
初期製程以簡單混合法進行調製，惟於高濃度條件下易導致粒徑增大與聚集不均，故進一步導入MUCU製程（混合、超音波震盪、離心、再震盪）進行優化。結果顯示，未加入鈣離子時，MUCU法可將粒徑穩定控制於250 nm左右，並提升分散穩定性；若加入Ca²⁺進行離子交聯則可於簡單混合條件下製得穩定粒子。
藉由調整SA/PL比例（1.2–14.4）與Ca²⁺濃度（0.23–0.83 mM），本研究選用SA/PL 重量比為6與9.6、Ca²⁺ 濃度為0與0.34 mM兩條件作為代表樣品，用以比較鈣離子對SAPL載體性質之影響。粒徑與Zeta電位分析顯示，載藥後SAPL奈米粒子仍維持200–300 nm大小與−55至−74 mV負電位，具良好粒子穩定性。於0.35%投藥濃度下，SAPL6-0.26 mM Ca與SAPL13.2-0.51 mM Ca之包覆效率分別為4.38%與4.56%，最高負載量達30.48%，顯示Ca²⁺交聯有助穩定藥物並提升包覆效率。
釋放實驗結果顯示，SAPL與SAPL-Ca奈米粒子於PBS、模擬腦脊液（CSF）與模擬鼻液（SNF）中，48小時內皆可達80%以上之累積釋放，且SAPL9.6-0.34 mM Ca具明顯緩釋效果，推測與Ca²⁺於SA鏈段形成蛋盒結構有關。細胞毒性評估顯示SAPL與SAPL-Ca奈米粒子於180 μg/mL以下濃度對INS-1與RPMI-2650細胞皆具良好相容性，細胞存活率高於80%。GSIS實驗進一步證實SAPL6與SAPL9.6-0.34 mM Ca載藥系統可有效遞送DZX-Li至INS-1細胞，且藥效未因包覆而降低。
最後以RPMI-2650細胞建立Transwell氣液介面鼻上皮模型進行藥物滲透實驗，結果顯示SAPL6與SAPL9.6-0.34 mM Ca載藥奈米粒子之滲透率分別為2.79 × 10-5 cm/s 與3.16 × 10-5 cm/s ，與游離Li -DZX之2.48 × 10-5 cm/s相近，並無顯著差異，顯示SAPL載體不影響藥物穿透效率，且此數值高於游離DZX之1.1 × 10-5 cm/s以及文獻中常見之標準模型如 Calu-3 或 RPMI 2650 細胞中transcellular 標記物Propranolol 所呈現之穿透率（約14.4–16.1*10⁻⁶ cm/s），證實此載藥系統為高度通透性，具鼻腦遞送潛力。
綜合而言，本研究建立之SAPL奈米粒子遞藥系統具備製程簡便、粒徑穩定、藥效維持、緩釋可控、細胞相容性佳與穿透效率良好等優勢，為Diazoxide或其他中樞神經治療藥物開發鼻腔遞送策略提供一具潛力之平台。

This study developed a nasal drug delivery system using sodium alginate (SA) and ε-polylysine (PL) to form SAPL nanoparticles via electrostatic self-assembly for encapsulating diazoxide lithium salt (Li-DZX). Rhodamine 6G hydrazide (R6G) was conjugated for fluorescence tracking. A MUCU process (mixing, ultrasonication, centrifugation, re-ultrasonication) improved particle stability (~250 nm). Formulations with and without calcium (e.g., SAPL6, SAPL9.6-0.34 mM Ca) showed good colloidal stability (−55 to −74 mV) and achieved up to 30.48% drug loading. In vitro release exceeded 80% in 48 h, with Ca²⁺-crosslinked particles showing sustained release.
Cytotoxicity and GSIS assays confirmed biocompatibility and retained drug activity. Transwell tests demonstrated comparable permeability to free drug. This SAPL system shows promise for intranasal delivery of CNS drugs.

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