Mesoporous Silica Nanoparticles‐Based Formulations for Enhanced Oral Delivery of Peptide Drugs: A Case Study on Insulin
Source abstract
Abstract
ABSTRACT Peptide drugs have revolutionized modern medicine owing to their high potency, selectivity, and excellent tolerability. However, oral delivery remains limited, and most peptide drugs are administered parenterally due to their inherent instability to proteolytic digestion and poor ability to cross gastrointestinal barriers, which hinders efficient absorption into the bloodstream. This study presents a multifunctional oral delivery system based on mesoporous silica nanoparticles (MSN) customized for insulin administration. Insulin‐loaded MSN were co‐formulated with succinylated β‐lactoglobulin to produce pH‐responsive tablets that limited premature gastric release (≤13% after 2 h at pH 1.2) and protected insulin from enzymatic degradation, while enabling controlled intestinal release (up to 88%–98% at pH 7.4). Surface functionalization with polyethylene glycol and phosphonate moieties improved colloidal stability and increased insulin solubility by ∼2.5‐fold. The interaction of phosphonated MSN with intestinal epithelial cells further induced transient reorganization of tight junction proteins, enhancing paracellular insulin transport (26% after 24 h, compared with 13% for non‐confined insulin). Delivered insulin retained bioactivity, as demonstrated by activation of insulin‐responsive signaling pathways in vitro and reduced blood glucose levels in hyperglycemic mice. These results highlight MSN as a promising platform for oral peptide delivery with improved efficacy and patient compliance.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Advanced Drug Delivery Systems · Proteins in Food Systems · Drug Solubulity and Delivery Systems
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Functional Materials and Catalysis Faculty of Chemistry University of Vienna Vienna Austria
Vienna Doctoral School in Chemistry (DoSChem) University of Vienna Vienna Austria
Department of Analytical Chemistry Faculty of Chemistry University of Vienna Vienna Austria
Joint Metabolome Facility University of Vienna and Medical University of Vienna Vienna Austria
Institute of Biological Chemistry Faculty of Chemistry University of Vienna Vienna Austria
Department of Environmental Toxicology College of Agriculture and Environmental Science University of California Davis California USA
Department of Anatomy Physiology and Cell Biology School of Veterinary Medicine University of California Davis California USA
Centre For Microbiology and Environmental Systems Science Department of Microbiology and Ecosystem Science Division of Microbial Ecology University of Vienna Vienna Austria
Department of Organic Chemistry Faculty of Chemistry University of Vienna Vienna Austria
Department of Food Chemistry and Toxicology Faculty of Chemistry University of Vienna Vienna Austria
Institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia
Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna Vienna Austria
Core Facility Multimodal Imaging Faculty of Chemistry University of Vienna Vienna Austria
Funding
European Research Council · Australian Research Council · National Health and Medical Research Council · Austrian Science Fund · Universität Wien
References (100+)
Show source-provided references
1. 10.1016/j.drudis.2021.01.02010.1016/j.drudis.2021.01.020 ↗
2. 10.1016/j.addr.2020.05.00710.1016/j.addr.2020.05.007 ↗
3. 10.1016/j.ijpharm.2014.10.05910.1016/j.ijpharm.2014.10.059 ↗
4. 10.1002/adma.20190193510.1002/adma.201901935 ↗
5. 10.1038/s41392‐022‐00904‐410.1038/s41392‐022‐00904‐4 ↗
6. 10.1038/s41573‐020‐00135‐810.1038/s41573‐020‐00135‐8 ↗
7. 10.1021/acs.jmedchem.1c0076710.1021/acs.jmedchem.1c00767 ↗
8. 10.1002/anie.20241533310.1002/anie.202415333 ↗
9. 10.1039/9781837674541-0002310.1039/9781837674541-00023 ↗
10. 10.1038/s41573‐019‐0053‐010.1038/s41573‐019‐0053‐0 ↗
11. 10.2337/cd19‐007910.2337/cd19‐0079 ↗
12. 10.2337/cd22‐011810.2337/cd22‐0118 ↗
13. 10.1016/j.diabres.2023.11060510.1016/j.diabres.2023.110605 ↗
14. 10.2147/DDDT.S47082610.2147/DDDT.S470826 ↗
15. 10.3390/pharmaceutics1502048410.3390/pharmaceutics15020484 ↗
16. 10.1038/s41578‐019‐0156‐610.1038/s41578‐019‐0156‐6 ↗
17. 10.1038/s41581‐020‐0278‐510.1038/s41581‐020‐0278‐5 ↗
18. 10.1038/s41574‐021‐00542‐w10.1038/s41574‐021‐00542‐w ↗
19. 10.1002/anie.20200887910.1002/anie.202008879 ↗
20. 10.1002/ddr.2190310.1002/ddr.21903 ↗
21. 10.1016/j.ijbiomac.2023.12511410.1016/j.ijbiomac.2023.125114 ↗
22. 10.1016/j.jconrel.2020.07.02110.1016/j.jconrel.2020.07.021 ↗
23. 10.1016/j.addr.2023.11511510.1016/j.addr.2023.115115 ↗
24. 10.1038/s41551‐019‐0465‐510.1038/s41551‐019‐0465‐5 ↗
25. 10.1021/acs.nanolett.3c0083510.1021/acs.nanolett.3c00835 ↗
26. 10.1039/d5nj00654f10.1039/d5nj00654f ↗
27. 10.1039/d3bm00137g10.1039/d3bm00137g ↗
28. 10.1021/acsami.1c0058010.1021/acsami.1c00580 ↗
29. 10.1016/j.jcis.2020.08.01010.1016/j.jcis.2020.08.010 ↗
30. 10.1021/acsnano.3c0240310.1021/acsnano.3c02403 ↗
31. 10.1002/smsc.20240011210.1002/smsc.202400112 ↗
32. 10.1002/chem.20200077310.1002/chem.202000773 ↗
33. 10.1021/acs.chemmater.6b0087710.1021/acs.chemmater.6b00877 ↗
34. 10.1016/j.jcis.2020.12.00410.1016/j.jcis.2020.12.004 ↗
35. 10.1039/c9bm00274j10.1039/c9bm00274j ↗
36. 10.1016/j.jcis.2017.11.06510.1016/j.jcis.2017.11.065 ↗
37. 10.1515/pac‐2014‐111710.1515/pac‐2014‐1117 ↗
38. 10.1007/s10450‐014‐9606‐z10.1007/s10450‐014‐9606‐z ↗
39. 10.1016/j.jcis.2023.04.15810.1016/j.jcis.2023.04.158 ↗
40. 10.1021/acsomega.8b0278410.1021/acsomega.8b02784 ↗
41. 10.1038/s41598‐017‐18502‐810.1038/s41598‐017‐18502‐8 ↗
42. 10.1016/j.colsurfa.2015.07.04210.1016/j.colsurfa.2015.07.042 ↗
43. 10.3390/pharmaceutics1002005710.3390/pharmaceutics10020057 ↗
44. 10.1016/j.cplett.2017.01.00210.1016/j.cplett.2017.01.002 ↗
45. 10.1021/acs.molpharmaceut.3c0001710.1021/acs.molpharmaceut.3c00017 ↗
46. On the Relationship Between pH‐Dependent β‐Lactoglobulin Self Assembly and Gelation Dynamics
47. 10.1016/j.ijpharm.2012.07.03910.1016/j.ijpharm.2012.07.039 ↗
48. 10.3168/jds.2019‐1707010.3168/jds.2019‐17070 ↗
49. 10.3168/jds.2025‐2641510.3168/jds.2025‐26415 ↗
50. 10.1016/j.idairyj.2010.07.00210.1016/j.idairyj.2010.07.002 ↗
51. 10.1038/nprot.2006.20210.1038/nprot.2006.202 ↗
52. 10.1016/j.ijbiomac.2009.06.01310.1016/j.ijbiomac.2009.06.013 ↗
53. 10.1016/j.sajce.2024.08.01310.1016/j.sajce.2024.08.013 ↗
54. 10.1023/A:102645582259510.1023/A:1026455822595 ↗
55. 10.1016/0168‐3659(87)90035‐610.1016/0168‐3659(87)90035‐6 ↗
56. 10.1016/j.addr.2012.09.02810.1016/j.addr.2012.09.028 ↗
57. 10.1002/jps.260052121010.1002/jps.2600521210 ↗
58. 10.1016/S0928‐0987(01)00095‐110.1016/S0928‐0987(01)00095‐1 ↗
59. 10.1016/0168‐3659(87)90034‐410.1016/0168‐3659(87)90034‐4 ↗
60. 10.1016/0378‐5173(83)90064‐910.1016/0378‐5173(83)90064‐9 ↗
61. 10.1016/j.jconrel.2005.10.02910.1016/j.jconrel.2005.10.029 ↗
62. 10.1002/psc.274410.1002/psc.2744 ↗
63. 10.1177/193229682091387410.1177/1932296820913874 ↗
64. 10.1021/cm504572b10.1021/cm504572b ↗
65. 10.3390/biom1005067510.3390/biom10050675 ↗
66. 10.1021/acs.jmedchem.2c0009410.1021/acs.jmedchem.2c00094 ↗
67. 10.1016/j.foodchem.2010.10.04210.1016/j.foodchem.2010.10.042 ↗
68. 10.1007/s00204‐023‐03495‐310.1007/s00204‐023‐03495‐3 ↗
69. 10.1053/j.gastro.2009.11.05210.1053/j.gastro.2009.11.052 ↗
70. 10.1097/MIB.000000000000028110.1097/MIB.0000000000000281 ↗
71. 10.1172/JCI12084310.1172/JCI120843 ↗
72. 10.1080/23311932.2016.126769110.1080/23311932.2016.1267691 ↗
73. 10.1023/B:RJAC.0000031281.69081.d010.1023/B:RJAC.0000031281.69081.d0 ↗
74. 10.1016/j.jpha.2019.08.00210.1016/j.jpha.2019.08.002 ↗
75. 10.1038/s41575‐021‐00539‐w10.1038/s41575‐021‐00539‐w ↗
76. 10.1038/ncomms169810.1038/ncomms1698 ↗
77. 10.1002/1873‐3468.1326810.1002/1873‐3468.13268 ↗
78. Temperature‐Dependence of ATP Level, Organic Phosphate Production and Na,K‐ATPase in Human Lymphocytes
79. 10.1146/annurev‐biochem‐052521‐03325010.1146/annurev‐biochem‐052521‐033250 ↗
80. 10.1039/d0cs01127d10.1039/d0cs01127d ↗
81. 10.1021/acs.molpharmaceut.6b0116510.1021/acs.molpharmaceut.6b01165 ↗
82. 10.1016/j.chemosphere.2020.12849710.1016/j.chemosphere.2020.128497 ↗
83. 10.1371/journal.pone.025782410.1371/journal.pone.0257824 ↗
84. 10.1016/j.foodres.2025.11620610.1016/j.foodres.2025.116206 ↗
85. 10.3892/mmr.2017.742010.3892/mmr.2017.7420 ↗
86. 10.1080/02648725.2000.1064800110.1080/02648725.2000.10648001 ↗
87. 10.1002/jps.2448410.1002/jps.24484 ↗
88. 10.1074/jbc.m10441620010.1074/jbc.m104416200 ↗
89. 10.1007/s10565‐014‐9277‐210.1007/s10565‐014‐9277‐2 ↗
90. 10.1248/bpb.b18‐0017410.1248/bpb.b18‐00174 ↗
91. High Glucose Induced Human Breast Cancer Cell MCF‐7 Viability, Migration and Invasion via the Expression of AKT, MAPKs and STAT3
92. 10.1042/BSR2019043610.1042/BSR20190436 ↗
93. 10.4172/1948‐5956.100026510.4172/1948‐5956.1000265 ↗
94. 10.4236/jbm.2025.13601910.4236/jbm.2025.136019 ↗
95. 10.3390/pharmaceutics1509218610.3390/pharmaceutics15092186 ↗
96. 10.31083/j.fbl280818010.31083/j.fbl2808180 ↗
97. 10.3390/ijms23181096510.3390/ijms231810965 ↗
98. 10.3390/cells809101710.3390/cells8091017 ↗
99. 10.1038/s12276‐018‐0126‐x10.1038/s12276‐018‐0126‐x ↗
100. 10.14814/phy2.1471710.14814/phy2.14717 ↗