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Published on: June 23, 2018
Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic
Jillian Collins1, Jessie M Barra2, Keifer Holcomb1
1Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, Colorado 80401, United States.
Abstract:
Targeting current therapies to treat or prevent the 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) in which 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 to 300 nm with a polydispersity index under 0.2. The NCs are nontoxic, stable in media culture, and can be lyophilized and reconstituted. NCs coated with a 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.
Insights
Researchers developed novel nanocapsules for targeted delivery to pancreatic beta cells, crucial for treating Type 1 Diabetes (T1D). These versatile nanocapsules offer a new platform for drug delivery and testing targeting peptides.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Endocrinology
Background:
- Type 1 Diabetes (T1D) involves the loss of pancreatic islet beta cells, necessitating targeted therapies.
- Current beta-cell targeting strategies are limited by a lack of specific targets and delivery vehicles.
- Developing methods for precise beta-cell delivery is key to improving T1D treatment efficacy and reducing side effects.
Purpose of the Study:
- To create a tailorable nanocapsule system for specific delivery to pancreatic beta cells.
- To enable interchangeable attachment of various targeting peptides for versatile delivery.
- To establish a platform for screening cell-targeting peptides and improving drug delivery.
Main Methods:
- Fabrication of polycaprolactone nanocapsules (NCs) with a cationic surfactant shell.
- Attachment of targeting moieties like Exendin-4 and an antibody for ENPD3.
- In vitro testing of NC uptake by human islet beta cells and stem cell-derived beta-like cells (sBCs).
- In vivo assessment of Exendin-4 coated NCs in mouse models.
Main Results:
- NCs demonstrated specific uptake by human and stem cell-derived beta cells in vitro.
- Successful delivery of both hydrophobic and hydrophilic cargo to beta cells was achieved.
- Exendin-4 coated NCs showed stability and targeted mouse pancreatic beta cells in vivo.
- NCs were nontoxic, stable in culture, and could be lyophilized and reconstituted.
Conclusions:
- Tailorable nanocapsules offer a promising approach for targeted drug delivery to pancreatic beta cells.
- The developed NC system serves as a valuable platform for screening beta-cell targeting peptides.
- This technology has the potential to advance T1D therapies by improving treatment efficacy and specificity.
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