Investigation Of Vitamin B 12 -Modified Amphiphilic Sodium Alginate Derivatives For Enhancing The Oral Delivery Efficacy Of Peptide Drugs.

Autor: Long L; 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., Lai M; Department of Polymer and Material Science, School of Chemistry, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Provincial Key Laboratory for High Performance Polymer-based Composites, Sun Yat-sen University, Guangzhou 510275, People's Republic of China., Mao X; Faculty of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China., Luo J; Department of Polymer and Material Science, School of Chemistry, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Provincial Key Laboratory for High Performance Polymer-based Composites, Sun Yat-sen University, Guangzhou 510275, People's Republic of China., Yuan X; Department of Scientific Research Center and Orthopedic, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People's Republic of China., Zhang LM; Faculty of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People's Republic of China., Ke Z; Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, People's Republic of China., Yang L; Department of Polymer and Material Science, School of Chemistry, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Provincial Key Laboratory for High Performance Polymer-based Composites, Sun Yat-sen University, Guangzhou 510275, People's Republic of China., Deng DY; 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.
Jazyk: angličtina
Zdroj: International journal of nanomedicine [Int J Nanomedicine] 2019 Sep 20; Vol. 14, pp. 7743-7758. Date of Electronic Publication: 2019 Sep 20 (Print Publication: 2019).
DOI: 10.2147/IJN.S218944
Abstrakt: Purpose: 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 12 -modified amphiphilic sodium alginate derivative (CSAD-VB 12 ) was synthesized.
Materials and Methods: A vitamin B 12 -modified amphiphilic sodium alginate derivative (CSAD-VB 12 ) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1 H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB 12 (CSAD-VB 12 /insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB 12 /insulin as spherical nanoparticles. The CSAD-VB 12 derivatives and CSAD-VB 12 /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 12 /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.
Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB 12 derivatives and CSAD-VB 12 /insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB 12 /insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB 12 /insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy.
Conclusion: CSAD-VB 12 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.
Competing Interests: The authors report no conflicts of interest in this work.
(© 2019 Long et al.)
Databáze: MEDLINE
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