利用同軸電噴灑技術製備包覆薑黃素之雙層膜奈米載體

Abstract

薑黃素(curcumin)具抗氧化、抗發炎、抗癌等功效，近年來被廣泛運用於保健食品及藥物中，但對於此類能有效預防慢性疾病的生物活性物質而言，低溶解度卻限制了其應用性。這些生物活性物質的口服生物有效性(oral bioavailbility)能透過與適當的載體系統結合進行改善，近幾年來科學家們積極嘗試設計具有多層膜及較小顆粒的載體系統，以增強對這類物質的保護作用以及在腸道中吸收的效果，在這樣的概念下，奈米級載體系統也被廣泛研究，奈米顆粒(nanoparticle)載體包覆生物活性物質、敏感性成分或藥物，因其粒徑小、總表面積大，可有效提升生物可利用率及生物可及性，但製備方法上需要繁瑣的操作程序以及巨大的能量花費，為了增加其效率因而發展出同軸電噴灑(coaxial electrospray)。同軸電噴灑能以簡單的一步驟製備出雙層膜(bilayer)的奈米顆粒載體，在食品科學中是一項非常新穎的技術。本研究中除採用此技術進行雙層膜奈米顆粒載體的製作外，也應用中央合成設計試驗的反應曲面法(CCD-RSM)以最適化雙層膜奈米顆粒載體的操作參數。幾丁聚醣(chitosan)與褐藻酸(alginate)兩種聚合物具備生物可分解性(biocompatibility)，分別做為載體中核層(core)及殼層(shell)部分，能有效保護薑黃素使其能通過胃部酸性環境到達腸道被人體所利用。透過反應曲面法分析後最適化的參數－供應電壓27 kV、針頭到搜集器距離20 cm、2%幾丁聚醣濃度、3%褐藻酸濃度、內針流速1：外針流速11－能產生以這兩種物質所製造的雙層膜載體到達112.1 ± 35.2 nm之粒徑。另外顆粒表面型態及雙層膜構造分別以掃描式電子顯微鏡(SEM)及穿透式電子顯微鏡(TEM)進行觀察，對於薑黃素之包覆效率也可到達86.4%。總結而言，透過同軸電噴灑能成功製造出具備雙層膜狀構造之奈米顆粒載體，包覆藥物的效果良好，並且透過CCD-RSM能夠最適化整個技術製程，達到最小顆粒粒徑及最佳包覆效率之目標。本研究的結果將能更強力地支持這項創新技術－同軸電噴灑，包覆如薑黃素等生物活性物質的效益，並透過這項技術製造雙層膜奈米顆粒載體方法之確立，期望將來得以運用在其他藥物或生物活性物質的保護上，以為後續食品、醫藥界之用。

Curcumin is recognized as a potential bioactive compound in the field of pharmacy and food technology, since it has a plenty of beneficial effects toward humans. However, the realization of using this natural bioactive compound to prevent the development of chronic diseases is most of the time constrained by the pool oral bioavailability. The oral bioavailability could be enhanced through the incorporation of suitable carrier system. To improve the ability to protect and the rate of intestinal absorption, designing carrier systems that have multiple layers and lower particle size has become the popular trend in recent decades. In this sense, the nano-scopic bilayer carrier system then catches the attention of many investigators. Nonetheless, the preparation of the nano-sized bilayer system commonly requires multiple operations and intense energy input. To improve the efficiency, coaxial electrospraying was developed as the novel method that utilize only one simple step to manufacture nanoparticles with dual layers. In present work, the process of generating bilayered nanoparticles was optimized using CCD-RSM. Biocompatible polymers, chitosan and alginate, were arranged into the core and shell part of the carrier for better protection of the contained curcumin through the gastrointestinal tract. Through the RSM analysis, the optimum processing parameters to prepare the chitosan/ alginate bilayer carrier with 112.1 ± 35.2 nm diameter were efficiently set at 27 kV of applied voltage, 20 cm tip-to-collector distance, 2% inner polymer concentration, and 3% outer polymer concentration. The speed ratio of inner and outer polymers passing through the concentric needle was 1:11. The surface morphology and dual layer structure were observed using SEM and TEM. The encapsulation efficiency of curcumin reached 86.4%. In summary, this work has successfully developed the efficient production process to produce bilayer nanoparticles using co-axial electrospraying combine with CCD-RSM analysis. The result from this work could serve as the strong foundation to promote this innovative technique, electrospraying, for the preparation of oral formulations containing diverse bioactive components, such as curcumin.