Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell
Targeting of current therapies to treat or prevent loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off target effects. Current efforts to target the β-cell are limited by a lack of β-cell specific targets and the inability to test multiple targeting...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2024
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| _version_ | 1811141239565713408 |
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| author | Collins, J Barra, JM Holcomb, K Shilleh, A Hodson, D Farnsworth, NL |
| author_facet | Collins, J Barra, JM Holcomb, K Shilleh, A Hodson, D Farnsworth, NL |
| author_sort | Collins, J |
| collection | OXFORD |
| description | Targeting of current therapies to treat or prevent loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide
improved efficacy and reduce off target effects. Current efforts to target the β-cell are limited by a lack of β-cell specific targets and
the inability to test multiple targeting moieties with the same delivery vehicle. Here we fabricate a tailorable polycaprolactone
nanocapsule (NC) where multiple different targeting peptides can be interchangeably attached for β-cell specific delivery. Incorporation of a cationic surfactant in the NC shell allows for the attachment of Exendin-4 and an antibody for ectonucleoside triphosphate
diphosphohydrolase 3 (ENTPD3) for β-cell specific targeting. The average NC size ranges from 250-300nm with a polydispersity
index under 0.2. The NCs are non-toxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with targeting
peptide were taken up by human cadaveric islet β-cells and human stem cell-derived β-like cells (sBC) in vitro with a high level of
specificity. Furthermore, NCs successfully delivered both hydrophobic and hydrophilic cargo to human β-cells. Additionally, Exendin-4 coated NCs were stable and targeted the mouse pancreatic islet β-cell in vivo. Overall, our tailorable NCs have the potential to
improve cell-targeted drug delivery and can be utilized as a screening platform to test the efficacy of cell targeting peptides. |
| first_indexed | 2024-09-25T04:34:43Z |
| format | Journal article |
| id | oxford-uuid:35781e50-e108-4bca-9cad-58c0b00d1804 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:34:43Z |
| publishDate | 2024 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:35781e50-e108-4bca-9cad-58c0b00d18042024-09-19T15:48:07ZPeptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cellJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:35781e50-e108-4bca-9cad-58c0b00d1804EnglishSymplectic ElementsAmerican Chemical Society2024Collins, JBarra, JMHolcomb, KShilleh, AHodson, DFarnsworth, NLTargeting of current therapies to treat or prevent loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off target effects. Current efforts to target the β-cell are limited by a lack of β-cell specific targets and the inability to test multiple targeting moieties with the same delivery vehicle. Here we fabricate a tailorable polycaprolactone nanocapsule (NC) where multiple different targeting peptides can be interchangeably attached for β-cell specific delivery. Incorporation of a cationic surfactant in the NC shell allows for the attachment of Exendin-4 and an antibody for ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) for β-cell specific targeting. The average NC size ranges from 250-300nm with a polydispersity index under 0.2. The NCs are non-toxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with targeting peptide were taken up by human cadaveric islet β-cells and human stem cell-derived β-like cells (sBC) in vitro with a high level of specificity. Furthermore, NCs successfully delivered both hydrophobic and hydrophilic cargo to human β-cells. Additionally, Exendin-4 coated NCs were stable and targeted the mouse pancreatic islet β-cell in vivo. Overall, our tailorable NCs have the potential to improve cell-targeted drug delivery and can be utilized as a screening platform to test the efficacy of cell targeting peptides. |
| spellingShingle | Collins, J Barra, JM Holcomb, K Shilleh, A Hodson, D Farnsworth, NL Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title | Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title_full | Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title_fullStr | Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title_full_unstemmed | Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title_short | Peptide coated polycaprolactone-benzalkonium chloride nanocap-sules for targeted drug delivery to the pancreatic β-cell |
| title_sort | peptide coated polycaprolactone benzalkonium chloride nanocap sules for targeted drug delivery to the pancreatic β cell |
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