口服給藥在藥物傳輸系統中具有高度的病患依從性與方便性的優勢，並且在商業上具有巨大的價值。然而，許多藥物在消化道中存在溶解度差、滲透率差等問題，導致其生物利用度不佳。聚乳酸-羥基乙酸共聚物(Poly (lactic-co-glycolic acid), PLGA)以奈米粒子形式在許多研究中被證實能夠保護藥物在口服給藥路徑中免於流失，並避免藥物在消化道中被豐富的酵素分解。然而，PLGA奈米粒子在腸道上皮細胞中仍然難以被內吞並轉運至體循環中。本研究利用免疫球蛋白A (Immunoglobulin A, IgA)以二聚體形式在腸道上皮細胞上透過受體介導轉胞吞運送(receptor-mediated transcytosis)的特性，增加生物利用度。藥物載體的設計利用奈米沉澱法製作PLGA奈米粒子，並透過碳二亞胺化學法使IgA共價結合在PLGA奈米粒子表面上。
本研究製作兩種不同IgA共價結合量的奈米粒子，分別為Low IgA-NP (1mg的PLGA表面有744.53 ± 32.65 ng的IgA)與High IgA-NP (1mg的PLGA表面有1683.71 ± 70.65 ng的IgA)，在人結腸癌細胞(C2Bbe1)轉胞吞實驗顯示Low IgA-NP的轉胞吞效率較佳，因此後續實驗以Low IgA-NP進行。結果顯示，Low IgA-NP具有均一的粒徑分佈與能夠使奈米粒子穩定分散的表面電位(> ± 30 mV) ，粒徑為175.9 ± 13.25 nm，PdI為0.07 ± 0.03，表面電位為 -36.6 ± 4.61 mV。並且於含有酵素的模擬腸胃液下，Low IgA-NP也呈現均勻的粒徑分佈，PdI為0.15 ± 0.04。IgA共價結合於PLGA奈米粒子表面上的含量較加入模擬腸胃液前仍保留65.47 ± 7.39%。然而，在SEM影像中發現經過含有酵素的模擬腸胃液後，Low IgA-NP的形貌明顯改變，並造成了OVA釋放含量與未加酵素的模擬腸胃液組別相比明顯從28.19 ± 0.97%上升至64.54 ± 4.38%。
在人結腸癌細胞(C2Bbe1)轉胞吞運送的實驗中，在48小時內Low IgA-NP相較OVA NP轉胞吞運送效率顯著從3.97 ± 2.60%提升至50.08 ± 2.69%，並在共軛焦顯微鏡與定量螢光強度的結果，觀察到隨著奈米粒子培養的時間增加，Low IgA-NP有轉胞吞運送的現象。因此以上研究證實，透過IgA共價結合的PLGA奈米粒子能夠於腸道上皮細胞轉胞吞運送，有望成為提升口服藥物效率的一種潛在策略，為未來藥物傳輸系統的開發提供了新的方向和可能性。

Oral drug delivery offers advantages like patient compliance and commercial value but faces challenges with drug solubility and low bioavailability due to degradation in the gastrointestinal tract. While PLGA nanoparticles protect drugs from enzymatic breakdown, they struggle with transcytosis across intestinal epithelial cells. This study addresses this issue by using dimeric Immunoglobulin A (IgA) to enhance receptor-mediated transcytosis. PLGA nanoparticles were synthesized via nanoprecipitation, and IgA was conjugated to their surface using carbodiimide chemistry. This study developed two types of nanoparticles with varying IgA conjugation amounts: Low IgA-NP (744.53 ± 32.65 ng/mg PLGA) and High IgA-NP (1683.71 ± 70.65 ng/mg PLGA). Transcytosis experiments demonstrated that Low IgA-NP exhibited better transcytosis efficiency, thus subsequent experiments were conducted with Low IgA-NP. The results demonstrated that Low IgA-NP exhibited a uniform particle size distribution and a significant zeta potential that enabled stable dispersion of the nanoparticles (> ± 30 mV). The particle size was 175.9 ± 13.25 nm, PdI was 0.07 ± 0.03, and zeta potential was -36.6 ± 4.61 mV. Moreover, in simulated gastrointestinal fluid with enzymes, Low IgA-NP also exhibited a uniform particle size distribution, with a PdI of 0.15 ± 0.04. The amount of IgA conjugated to the PLGA nanoparticles was maintained at 65.47 ± 7.39%. However, SEM images revealed that the morphology of Low IgA-NP significantly changed after exposure to enzyme-containing simulated gastrointestinal fluid, resulting in a significant increase in OVA release from 28.19 ± 0.97% to 64.54 ± 4.38% compared to the group without enzymes. In transcytosis experiments using human colon cells (C2Bbe1), the transcytosis efficiency of Low IgA-NP was significantly improved from 3.97 ± 2.60% to 50.08 ± 2.69% over 48 hours compared to OVA NP. Confocal microscopy and quantitative fluorescence intensity results indicated that Low IgA-NP exhibited the phenomenon of transcytosis. Therefore, this study confirms that PLGA nanoparticles conjugated with IgA can facilitate transcytosis in intestinal epithelial cells, promising to be a potential strategy for enhancing oral drug delivery efficiency. This provides new directions and possibilities for the development of future drug delivery systems.

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