Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid
Zuxian Chen,1,* Shangcong Han,1,* Xiaotang Yang,1 Lisa Xu,1 Hong Qi,2 Guizhou Hao,3 Jie Cao,1 Yan Liang,1 Qingming Ma,1 Guimin Zhang,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, People’s Republic of China; 2Department of General Surgery,...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2020
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/97a093e1ded441079eb8bc89b7f42bfb |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:97a093e1ded441079eb8bc89b7f42bfb |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:97a093e1ded441079eb8bc89b7f42bfb2021-12-02T08:42:11ZOvercoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid1178-2013https://doaj.org/article/97a093e1ded441079eb8bc89b7f42bfb2020-07-01T00:00:00Zhttps://www.dovepress.com/overcoming-multiple-absorption-barrier-for-insulin-oral-delivery-using-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zuxian Chen,1,* Shangcong Han,1,* Xiaotang Yang,1 Lisa Xu,1 Hong Qi,2 Guizhou Hao,3 Jie Cao,1 Yan Liang,1 Qingming Ma,1 Guimin Zhang,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, People’s Republic of China; 2Department of General Surgery, Qingdao Municipal Hospital, Qingdao 266071, People’s Republic of China; 3Department of Scientific Research, Lunan Pharmaceutical Corporation, Linyi 276001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Sun Tel +86-532-82991203Email sunyong@qdu.edu.cnBackground: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system.Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques.Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin.Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.Keywords: insulin, oral drug delivery, transepithelial transport, paracellular pathway, caveolae-mediated transportChen ZHan SYang XXu LQi HHao GCao JLiang YMa QZhang GSun YDove Medical Pressarticleinsulinoral drug deliverytransepithelial transportparacellular pathwaycaveolae-mediated transportMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4877-4898 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
insulin oral drug delivery transepithelial transport paracellular pathway caveolae-mediated transport Medicine (General) R5-920 |
| spellingShingle |
insulin oral drug delivery transepithelial transport paracellular pathway caveolae-mediated transport Medicine (General) R5-920 Chen Z Han S Yang X Xu L Qi H Hao G Cao J Liang Y Ma Q Zhang G Sun Y Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| description |
Zuxian Chen,1,* Shangcong Han,1,* Xiaotang Yang,1 Lisa Xu,1 Hong Qi,2 Guizhou Hao,3 Jie Cao,1 Yan Liang,1 Qingming Ma,1 Guimin Zhang,3 Yong Sun1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, People’s Republic of China; 2Department of General Surgery, Qingdao Municipal Hospital, Qingdao 266071, People’s Republic of China; 3Department of Scientific Research, Lunan Pharmaceutical Corporation, Linyi 276001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Sun Tel +86-532-82991203Email sunyong@qdu.edu.cnBackground: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system.Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques.Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin.Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.Keywords: insulin, oral drug delivery, transepithelial transport, paracellular pathway, caveolae-mediated transport |
| format |
article |
| author |
Chen Z Han S Yang X Xu L Qi H Hao G Cao J Liang Y Ma Q Zhang G Sun Y |
| author_facet |
Chen Z Han S Yang X Xu L Qi H Hao G Cao J Liang Y Ma Q Zhang G Sun Y |
| author_sort |
Chen Z |
| title |
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| title_short |
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| title_full |
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| title_fullStr |
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| title_full_unstemmed |
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid |
| title_sort |
overcoming multiple absorption barrier for insulin oral delivery using multifunctional nanoparticles based on chitosan derivatives and hyaluronic acid |
| publisher |
Dove Medical Press |
| publishDate |
2020 |
| url |
https://doaj.org/article/97a093e1ded441079eb8bc89b7f42bfb |
| work_keys_str_mv |
AT chenz overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT hans overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT yangx overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT xul overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT qih overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT haog overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT caoj overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT liangy overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT maq overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT zhangg overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid AT suny overcomingmultipleabsorptionbarrierforinsulinoraldeliveryusingmultifunctionalnanoparticlesbasedonchitosanderivativesandhyaluronicacid |
| _version_ |
1718398427192098816 |