急性肺損傷是死亡率高的肺部疾病，臨床上仍無有效之治療方法，因此急需發展一套有效的治療策略。臨床病理上，急性肺損傷患者會出現肺泡及間質水腫、肺泡塌陷、細胞浸潤等情形，其病理機轉與肺部巨噬細胞(alveolar macrophage)之活化、細胞激素(cytokines)的釋放有極密切的關係。因此在臨床上常以抗發炎藥物治療急性肺損傷。厚朴酚(magnolol)已證實可以抑制巨噬細胞受刺激所產生之細胞激素及相關之發炎前驅物質，然而magnolol極為疏水，在水溶液環境中懸浮分散不佳，影響其在活體內之藥物分佈，因此臨應用上極為受限。因此如能開發出一個藥物載體可以有效解決magnolol疏水的特性，並提升藥物傳遞至巨噬細胞之效率，將有助於急性肺損傷的治療。聚縮酮(polyketal)為具酸鹼應答型之生物可降解高分子，降解後產生中性且可被人體吸收之副產物，因此生物相容性極高。以polyketal製備適合肺部傳輸之微米顆粒除了可以改善magnolol之懸浮特性外，更重要的是polyketal酸鹼應答及快速水解特性，使其可以在生理環境下維持藥物之穩定，一旦到達肺部巨噬細胞時，在吞噬溶酶體之酸性環境下可迅速將magnolol釋出，抑制肺部發炎因子，進而達到治療急性肺損傷之目的。
　　在本研究中利用微調式合成法製備具快速水解能力之polyketal共聚物，並利用此高分子製備出適合肺部傳輸之magnolol微米顆粒，並利用電子顯微鏡與高效能液相層析儀分析所製備之顆粒，結果顯示polyketal微粒大小為3.5± 0.417 μm，而magnolol包覆率約85± 8.44 %，在酸性的環境下(pH5.0)，magnolol可以在六小時內完全釋放。此外細胞實驗結果顯示，polyketal微米顆粒除了可以有效降低magnolol毒性外，在抑制NO的生成上，magnolol-polyketal微粒比free magnolol更能有效抑制NO的產生，達到抗發炎的效果。

Acute lung injury (ALI) is one of the leading causes of death in sepsis. Pro-inflammatory cytokines secreted by macrophages and consequently produced nitric oxide (NO) that play a major role in mediating acute lung injury. Magnolol has shown inhibitory effects on NO production in lipopolysaccharides (LPS)-activated macrophages, however, the poor solubility and the poor suspension properties of magnolol have hindered the success. Drug delivery systems that can target magnolol to macrophages have great clinical potential. Polyketals, a family of pH sensitive biodegradable polymers, have been used as drug delivery vehicles for the treatment of inflammatory diseases because they have excellent biocompatibility and do not generate inflammatory acid degradation products.Polyketal microparticles can be manipulated to the optimal sizes (1-5 μm) for pulmonary drug delivery by changing the preparation conditions. Microparticles formulated from polyketal copolymers should be suitable for treating acute lung injury because they rapidly hydrolyze and release magnolol in the phagolysosome of macrophages (pH 5.0), but remain stables at physiological conditions (pH 7.4). In this research, we successfully synthesized a polyketal copolymer with rapid hydrolysis rate, and used it to encapsulate magnolol. The results showed the particle size of magnolol-PKMs is 3.5 ± 0.417 μm and encapsulation efficiency of magnolol-PKMs is 85 ± 8.44 %. Also magnolol-PKMs exhibited a great aqueous dispensability and low cytotoxicity. The magnolol-PKMs also showed better inhibitory effects on NO production from LPS -activated RAW 264.7 cell when compared to free magnolol at same condition．

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