Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery
Here we introduce a new approach for transcutaneous drug delivery, using microneedles coated with stabilized lipid nanocapsules, for delivery of a model vaccine formulation. Poly(lactide-co-glycolide) microneedle arrays were coated with multilayer films via layer-by-layer assembly of a biodegradable...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/91495 https://orcid.org/0000-0003-0787-298X |
| _version_ | 1826215079437139968 |
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| author | DeMuth, Peter Charles Moon, James J. Suh, Heikyung Hammond, Paula T Irvine, Darrell J |
| author2 | Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies |
| author_facet | Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies DeMuth, Peter Charles Moon, James J. Suh, Heikyung Hammond, Paula T Irvine, Darrell J |
| author_sort | DeMuth, Peter Charles |
| collection | MIT |
| description | Here we introduce a new approach for transcutaneous drug delivery, using microneedles coated with stabilized lipid nanocapsules, for delivery of a model vaccine formulation. Poly(lactide-co-glycolide) microneedle arrays were coated with multilayer films via layer-by-layer assembly of a biodegradable cationic poly(β-amino ester) (PBAE) and negatively charged interbilayer-cross-linked multilamellar lipid vesicles (ICMVs). To test the potential of these nanocapsule-coated microneedles for vaccine delivery, we loaded ICMVs with a protein antigen and the molecular adjuvant monophosphoryl lipid A. Following application of microneedle arrays to the skin of mice for 5 min, (PBAE/ICMV) films were rapidly transferred from microneedle surfaces into the cutaneous tissue and remained in the skin following removal of the microneedle arrays. Multilayer films implanted in the skin dispersed ICMV cargos in the treated tissue over the course of 24 h in vivo, allowing for uptake of the lipid nanocapsules by antigen presenting cells in the local tissue and triggering their activation in situ. Microneedle-mediated transcutaneous vaccination with ICMV-carrying multilayers promoted robust antigen-specific humoral immune responses with a balanced generation of multiple IgG isotypes, whereas bolus delivery of soluble or vesicle-loaded antigen via intradermal injection or transcutaneous vaccination with microneedles encapsulating soluble protein elicited weak, IgG1-biased humoral immune responses. These results highlight the potential of lipid nanocapsules delivered by microneedles as a promising platform for noninvasive vaccine delivery applications. |
| first_indexed | 2024-09-23T16:16:12Z |
| format | Article |
| id | mit-1721.1/91495 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:16:12Z |
| publishDate | 2014 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/914952022-10-02T07:25:37Z Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery DeMuth, Peter Charles Moon, James J. Suh, Heikyung Hammond, Paula T Irvine, Darrell J Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Ragon Institute of MGH, MIT and Harvard Koch Institute for Integrative Cancer Research at MIT DeMuth, Peter Charles Moon, James J. Suh, Heikyung Hammond, Paula T. Irvine, Darrell J. Here we introduce a new approach for transcutaneous drug delivery, using microneedles coated with stabilized lipid nanocapsules, for delivery of a model vaccine formulation. Poly(lactide-co-glycolide) microneedle arrays were coated with multilayer films via layer-by-layer assembly of a biodegradable cationic poly(β-amino ester) (PBAE) and negatively charged interbilayer-cross-linked multilamellar lipid vesicles (ICMVs). To test the potential of these nanocapsule-coated microneedles for vaccine delivery, we loaded ICMVs with a protein antigen and the molecular adjuvant monophosphoryl lipid A. Following application of microneedle arrays to the skin of mice for 5 min, (PBAE/ICMV) films were rapidly transferred from microneedle surfaces into the cutaneous tissue and remained in the skin following removal of the microneedle arrays. Multilayer films implanted in the skin dispersed ICMV cargos in the treated tissue over the course of 24 h in vivo, allowing for uptake of the lipid nanocapsules by antigen presenting cells in the local tissue and triggering their activation in situ. Microneedle-mediated transcutaneous vaccination with ICMV-carrying multilayers promoted robust antigen-specific humoral immune responses with a balanced generation of multiple IgG isotypes, whereas bolus delivery of soluble or vesicle-loaded antigen via intradermal injection or transcutaneous vaccination with microneedles encapsulating soluble protein elicited weak, IgG1-biased humoral immune responses. These results highlight the potential of lipid nanocapsules delivered by microneedles as a promising platform for noninvasive vaccine delivery applications. Howard Hughes Medical Institute (Investigator) United States. Dept. of Defense (W911NF-07-D-0004) Ragon Institute of MGH, MIT, and Harvard National Institutes of Health (U.S.) (NIH AI095109) United States. Army Research Office. Institute for Soldier Nanotechnologies 2014-11-07T15:59:40Z 2014-11-07T15:59:40Z 2012-09 2012-06 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/91495 DeMuth, Peter C., James J. Moon, Heikyung Suh, Paula T. Hammond, and Darrell J. Irvine. “Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery.” ACS Nano 6, no. 9 (September 25, 2012): 8041–8051.© 2012 American Chemical Society. https://orcid.org/0000-0003-0787-298X en_US http://dx.doi.org/10.1021/nn302639r ACS Nano Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | DeMuth, Peter Charles Moon, James J. Suh, Heikyung Hammond, Paula T Irvine, Darrell J Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title | Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title_full | Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title_fullStr | Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title_full_unstemmed | Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title_short | Releasable Layer-by-Layer Assembly of Stabilized Lipid Nanocapsules on Microneedles for Enhanced Transcutaneous Vaccine Delivery |
| title_sort | releasable layer by layer assembly of stabilized lipid nanocapsules on microneedles for enhanced transcutaneous vaccine delivery |
| url | http://hdl.handle.net/1721.1/91495 https://orcid.org/0000-0003-0787-298X |
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