Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China.
J Nanobiotechnology. 2018 Mar 19;16(1):24. doi: 10.1186/s12951-018-0353-2.
Nanotechnology-based drug delivery systems have been widely used for oral and systemic dosage forms delivery depending on the mucoadhesive interaction, and keratin has been applied for biomedical applications and drug delivery. However, few reports have focused on the keratin-based mucoadhesive drug delivery system and their mechanisms of mucoadhesion. Thus, the mucoadhesion controlled kerateine (reduced keratin, KTN)/keratose (oxidized keratin, KOS) composite nanoparticles were prepared via adjusting the proportion of KTN and KOS to achieve controlled gastric mucoadhesion and drug release based on their different mucoadhesive abilities and pH-sensitive properties. Furthermore, the mechanisms of mucoadhesion for KTN and KOS were also investigated in the present study.
The composite keratin nanoparticles (KNPs) with different mass ratio of KTN to KOS, including 100/0 (KNP-1), 75/25 (KNP-2), 50/50 (KNP-3), and 25/75 (KNP-4), displayed different drug release rates and gastric mucoadhesion capacities, and then altered the drug pharmacokinetic performances. The stronger mucoadhesive ability of nanoparticle could supply longer gastric retention time, indicating that KTN displayed a stronger mucoadhesion than that of KOS. Furthermore, the mechanisms of mucoadhesion for KTN and KOS at different pH conditions were also investigated. The binding between KTN and porcine gastric mucin (PGM) is dominated by electrostatic attractions and hydrogen bondings at pH 4.5, and disulfide bonds also plays a key role in the interaction at pH 7.4. While, the main mechanisms of KOS and PGM interactions are hydrogen bondings and hydrophobic interactions in pH 7.4 condition and were hydrogen bondings at pH 4.5.
The resulting knowledge offer an efficient strategy to control the gastric mucoadhesion and drug release of nano drug delivery systems, and the elaboration of mucoadhesive mechanism of keratins will enable the rational design of nanocarriers for specific mucoadhesive drug delivery.
基于纳米技术的药物传递系统已广泛应用于口服和全身剂型的传递，这取决于黏膜黏附相互作用，角蛋白已应用于生物医学应用和药物传递。然而，很少有报道关注基于角蛋白的黏膜黏附药物传递系统及其黏膜黏附机制。因此，通过调节角蛋白还原物（KTN）和角蛋白氧化物（KOS）的比例，制备了具有控制胃黏膜黏附性和药物释放能力的角蛋白复合纳米粒子（KTN/KOS 复合纳米粒子），这是基于它们不同的黏膜黏附能力和 pH 敏感性。此外，本研究还研究了 KTN 和 KOS 的黏膜黏附机制。
不同 KTN 与 KOS 质量比的复合角蛋白纳米粒子（KNPs），包括 100/0（KNP-1）、75/25（KNP-2）、50/50（KNP-3）和 25/75（KNP-4），显示出不同的药物释放速率和胃黏膜黏附能力，从而改变了药物的药代动力学性能。纳米粒子更强的黏膜黏附能力可以提供更长的胃滞留时间，表明 KTN 的黏膜黏附能力强于 KOS。此外，还研究了 KTN 和 KOS 在不同 pH 条件下的黏膜黏附机制。在 pH4.5 时，KTN 与猪胃粘蛋白（PGM）的结合主要由静电吸引和氢键介导，二硫键在 pH7.4 时也起着关键作用。而 KOS 与 PGM 相互作用的主要机制是在 pH7.4 条件下的氢键和疏水相互作用，在 pH4.5 时是氢键。
这些研究结果为控制纳米药物传递系统的胃黏膜黏附性和药物释放提供了一种有效的策略，对角蛋白黏膜黏附机制的阐述将使特定黏膜黏附性药物传递的纳米载体的合理设计成为可能。
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