Zhongjun Cheng1,2,3, Xiaoliang Chen4, Dongliang Zhai4, Feiyan Gao1,3, Tingwang Guo1,3, Wenfeng Li1,3, Shilei Hao5,6, Jingou Ji7,8, Bochu Wang9,10. 1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China. 2. College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China. 3. Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China. 4. Department of Nuclear Medicine, Chongqing Cancer Institution, Chongqing, 400030, China. 5. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China. shilei_hao@cqu.edu.cn. 6. Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China. shilei_hao@cqu.edu.cn. 7. College of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China. 725_tiger@sina.com. 8. Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China. 725_tiger@sina.com. 9. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China. wangbc2000@126.com. 10. Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China. wangbc2000@126.com.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
Bioavailability; Controlled drug release; Kerateine; Keratose; Mucoadhesion
Authors: B Menchicchi; J P Fuenzalida; Kishore Babu Bobbili; A Hensel; Musti J Swamy; F M Goycoolea Journal: Biomacromolecules Date: 2014-09-04 Impact factor: 6.988
Authors: Ju Wang; Shilei Hao; Tiantian Luo; Tao Zhou; Xin Yang; Bochu Wang Journal: Mater Sci Eng C Mater Biol Appl Date: 2016-11-22 Impact factor: 7.328