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dc.contributor.authorChou, Jonathan J
dc.contributor.authorBerger, Adam G
dc.contributor.authorJalili-Firoozinezhad, Sasan
dc.contributor.authorHammond, Paula T
dc.date.accessioned2025-07-18T20:15:51Z
dc.date.available2025-07-18T20:15:51Z
dc.date.issued2021-11
dc.identifier.urihttps://hdl.handle.net/1721.1/161228
dc.description.abstractThe ability to coat scaffolds and wound dressings with therapeutic short interfering RNA (siRNA) holds much potential for applications in wound healing, cancer treatment, and regenerative medicine. Layer-by-layer (LbL) technology is an effective method to formulate polyelectrolyte thin films for local delivery of siRNA; however, the formation and efficacy of LbL coatings as drug delivery systems are highly contingent on the assembly conditions. Here, we investigate the effects of LbL assembly parameters on film composition and consequent siRNA-mediated gene knockdown efficiency in vitro. Films comprising poly(β-amino ester) (PBAE) and siRNA were built on polyglactin 910 (Vicryl) sutures consisting of poly(10% L-lactide, 90% glycolide). A fractional factorial design was employed, varying the following LbL assembly conditions: pH, ionic strength, PBAE concentration, and siRNA concentration. Effects of these parameters on PBAE loading, siRNA loading, their respective weight ratios, and in vitro siRNA-mediated knockdown were elucidated. The parameter effects were leveraged to create a rationally designed set of solution conditions that was predicted to give effective siRNA-mediated knockdown, but not included in any of the original experimental conditions. This level of knockdown with our rationally designed loading conditions (47%) is comparable to previous formulations from our lab while being simpler in construction and requiring fewer film layers, which could save time and cost in manufacturing. This study highlights the importance of LbL solution conditions in the preparation of surface-mediated siRNA delivery systems and presents an adaptable methodology for extending these electrostatically-assembled coatings to the delivery of other therapeutic nucleic acids. STATEMENT OF SIGNIFICANCE: Short interfering RNA (siRNA) therapeutics are powerful tools to silence aberrant gene expression in the diseased state; however, the clinical utility of these therapies relies on effective controlled delivery approaches. Electrostatic self-assembly through the layer-by-layer (LbL) process enables direct siRNA release from surfaces, but this method is highly dependent upon the specific solution conditions used. Here, we use a fractional factorial design to illustrate how these assembly conditions impact composition of siRNA-eluting LbL thin films. We then elucidate how these properties mediate in vitro transfection efficacy. Ultimately, this work presents a significant step towards understanding how optimization of assembly conditions for surface-mediated LbL delivery can promote transfection efficacy while reducing the processing and material required.en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionof10.1016/j.actbio.2021.08.042en_US
dc.rightsCreative Commons Attribution-Noncommercial-ShareAlikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePubMed Centralen_US
dc.titleA design approach for layer-by-layer surface-mediated siRNA deliveryen_US
dc.typeArticleen_US
dc.identifier.citationChou, Jonathan J, Berger, Adam G, Jalili-Firoozinezhad, Sasan and Hammond, Paula T. 2021. "A design approach for layer-by-layer surface-mediated siRNA delivery." Acta Biomaterialia, 135.
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Soldier Nanotechnologiesen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentHarvard-MIT Program in Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.relation.journalActa Biomaterialiaen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2025-07-18T20:09:28Z
dspace.orderedauthorsChou, JJ; Berger, AG; Jalili-Firoozinezhad, S; Hammond, PTen_US
dspace.date.submission2025-07-18T20:09:31Z
mit.journal.volume135en_US
mit.licenseOPEN_ACCESS_POLICY
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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