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Chylomicron-pretended nano-bio self-assembling vehicle to promote lymphatic transport and GALTs target of oral drugs.
Biomaterials ( IF 14.0 ) Pub Date : 2018-10-18 , DOI: 10.1016/j.biomaterials.2018.10.012
Yuling Mao 1 , Shuang Feng 1 , Shuai Li 2 , Qinfu Zhao 1 , Donghua Di 3 , Yanfeng Liu 2 , Siling Wang 1
Affiliation  

Lymphatic transport of oral drugs allows extraordinary gains in bioavailability and efficacy through avoidance of first-pass hepatic metabolism and preservation of drugs at lymphatic tissues against lymph-mediated diseases. Chylomicrons can transport dietary lipids absorbed from the intestine to the tissues through lymphatic circulation. Herein, we engineered for the first time a chylomicron-pretended mesoporous silica nanocarrier that utilizes the digestion, re-esterification, and lymphatic transport process of dietary triglyceride to promote lymphatic transport of oral drugs. Taking lopinavir (LNV) as a model antiretroviral drug with disadvantages such as poor solubility, high first-pass effect and off-target deposition, this vehicle exhibited several properties belonging to ideal nanocarriers, including high drug load, amorphous dispersion and controlled release in the gastrointestinal tract. Additionally, a nano-bio interaction was demonstrated between nanoparticles and a key protein involved in chylomicron assembly; this biochemical reaction in cellular was utilized for the first time to promote lymphatic transport of nanocarriers for oral delivery. As a result, the chylomicron-pretended nanocarrier afforded 10.6-fold higher oral bioavailability compared with free LNV and effectively delivered LNV to gut-associated lymphoid tissues, where HIV persists and actively evolves. This approach not only promises a potential application to HIV-infected individuals but also opens a new avenue to other lymph-mediated pathologies such as autoimmune diseases and lymphatic tumor metastasis.

中文翻译:

Chylomicron假装的纳米生物自组装载体可促进口服药物的淋巴运输和GALTs靶标。

口服药物的淋巴运输可避免肝脏的首过代谢,并且可以将药物保存在淋巴组织中以抵抗淋巴介导的疾病,从而可在生物利用度和功效方面取得非凡的增长。乳糜微粒可通过淋巴循环将从肠道吸收的饮食脂质转运至组织。在这里,我们首次设计了一种乳糜微粒假装的介孔二氧化硅纳米载体,该载体利用饮食甘油三酸酯的消化,再酯化和淋巴运输过程来促进口服药物的淋巴运输。以洛匹那韦(LNV)为模型的抗逆转录病毒药物,具有溶解性差,首过效应高和脱靶沉积等缺点,该载体表现出多种属于理想纳米载体的特性,包括高载药量,无定形的分散和在胃肠道的控制释放。此外,纳米粒子与乳糜微粒组装中涉及的关键蛋白质之间也表现出了纳米生物相互作用。这种在细胞中的生化反应首次被用于促进纳米载体的淋巴运输,以用于口服递送。结果,与游离LNV相比,含乳糜微粒的纳米载体提供了10.6倍的口服生物利用度,并有效地将LNV递送至肠道相关的淋巴组织,在该组织中,HIV持续存在并活跃地进化。这种方法不仅有望被HIV感染者潜在应用,而且为其他淋巴介导的病理学,例如自身免疫性疾病和淋巴瘤转移,开辟了一条新途径。纳米粒子与乳糜微粒组装中涉及的关键蛋白质之间表现出纳米生物相互作用;这种在细胞中的生化反应首次被用于促进纳米载体的淋巴运输,以用于口服递送。结果,与游离LNV相比,含乳糜微粒的纳米载体可提供10.6倍的口服生物利用度,并有效地将LNV传递至与肠道相关的淋巴组织,在该组织中,HIV持续存在并活跃地进化。这种方法不仅有望被HIV感染者潜在应用,而且为其他淋巴介导的病理学,例如自身免疫性疾病和淋巴瘤转移,开辟了一条新途径。纳米粒子与乳糜微粒组装中涉及的关键蛋白质之间表现出纳米生物相互作用;这种在细胞中的生化反应首次被用于促进纳米载体的淋巴运输,以用于口服递送。结果,与游离LNV相比,含乳糜微粒的纳米载体提供了10.6倍的口服生物利用度,并有效地将LNV递送至肠道相关的淋巴组织,在该组织中,HIV持续存在并活跃地进化。这种方法不仅有望被HIV感染者潜在应用,而且为其他淋巴介导的病理学,例如自身免疫性疾病和淋巴瘤转移,开辟了一条新途径。细胞中的这种生化反应首次被用于促进纳米载体的淋巴运输,以用于口服递送。结果,与游离LNV相比,含乳糜微粒的纳米载体提供了10.6倍的口服生物利用度,并有效地将LNV递送至肠道相关的淋巴组织,在该组织中,HIV持续存在并活跃地进化。这种方法不仅有望被HIV感染者潜在应用,而且为其他淋巴介导的病理学,例如自身免疫性疾病和淋巴瘤转移,开辟了一条新途径。细胞中的这种生化反应首次被用于促进纳米载体的淋巴运输,以用于口服递送。结果,与游离LNV相比,含乳糜微粒的纳米载体提供了10.6倍的口服生物利用度,并有效地将LNV递送至肠道相关的淋巴组织,在该组织中,HIV持续存在并活跃地进化。这种方法不仅有望被HIV感染者潜在应用,而且为其他淋巴介导的病理学,例如自身免疫性疾病和淋巴瘤转移,开辟了一条新途径。
更新日期:2018-10-19
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