Department of Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Department of Scientific Research Center and Orthopedic, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People's Republic of China.
Int J Nanomedicine. 2019 Sep 20;14:7743-7758. doi: 10.2147/IJN.S218944. eCollection 2019.
Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B-modified amphiphilic sodium alginate derivative (CSAD-VB) was synthesized.
A vitamin B-modified amphiphilic sodium alginate derivative (CSAD-VB) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB (CSAD-VB/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB/insulin as spherical nanoparticles. The CSAD-VB derivatives and CSAD-VB/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles.
They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB derivatives and CSAD-VB/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy.
CSAD-VB derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.
肽类药物已被用于治疗多种疾病。然而，由于人体胃肠道内的酸性环境和消化酶，肽类药物经口服给药的生物利用度较差，限制了其临床应用。为了提高肽类药物经口服给药的在胃肠道内的稳定性、生物利用度和靶向药物递送，合成了一种维生素 B 修饰的两亲性海藻酸钠衍生物（CSAD-VB）。
通过室温下的 N,N'-二环己基碳二亚胺活性法合成了一种维生素 B 修饰的两亲性海藻酸钠衍生物（CSAD-VB），并通过傅里叶变换红外光谱（FTIR）和氢核磁共振光谱（1H NMR）进行了表征。胰岛素被用作模型肽药物，并在 PBS（pH=7.4）中制备了带负电荷的载胰岛素 CSAD-VB（CSAD-VB/胰岛素）纳米粒。扫描电子显微镜（SEM）用于观察 CSAD-VB/胰岛素呈球形纳米粒。通过 CCK-8 试验，CSAD-VB 衍生物和 CSAD-VB/胰岛素纳米粒对人结肠腺癌细胞（Caco-2）表现出非毒性。Caco-2 细胞模型用于测量胰岛素、CSAD/胰岛素和 CSAD-VB/胰岛素的表观渗透（Papp）。此外，还使用共聚焦显微镜确认了肠上皮细胞的内吞作用。使用 1 型糖尿病小鼠来评估测试纳米粒的肠道吸收和保留效果。
它们的尺寸为 30-50nm，呈球形纳米粒。CSAD-VB 衍生物和 CSAD-VB/胰岛素纳米粒对人结肠腺癌细胞（Caco-2）表现出非毒性。与胰岛素和 CSAD/胰岛素纳米粒相比，CSAD-VB/胰岛素纳米粒在 Caco-2 细胞模型中表现出更高的透过肠上皮细胞的渗透能力。CSAD-VB/胰岛素纳米粒经口服给予 1 型糖尿病小鼠，可获得更高的肠道保留效果、靶向吸收和优异的疗效。
CSAD-VB 衍生物通过口服给药增强了肽类的小肠吸收效果和保留效果，表明其可能成为未来临床应用中口服肽类递送的有前途的候选物。
