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Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue

Laccetti, Benjamin and Kornfield, Julia (2021) Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue. Journal of the Mechanical Behavior of Biomedical Materials, 115 . Art. No. 104246. ISSN 1751-6161. https://resolver.caltech.edu/CaltechAUTHORS:20201208-105038922

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Abstract

The barrier characteristics of the cornea are interrogated using the impact of micro-particles into ex vivo porcine cornea. Using a commercial gene gun (BioRad; PDS1000), microparticles were accelerated and made to embed in target materials: either ballistic gelatin as a reference or corneal tissue. Statistical analysis of penetration of polydisperse spherical microparticles (5–22 μm dia.) with density of 2.5 g/cc, 4.2 g/cc, and 7.8 g/cc (soda-lime glass, barium-titanate glass and stainless steel; more limited examination of 1.1 g/cc polyethylene and 19.2 g/cc tungsten) spanned almost two decades in kinetic energy. Penetration profiles in ballistic gelatin show that the particle embedding depth is sensitive to particle size and density. In the cornea, penetration is a weak function of size and density, and the corneal stroma is an effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76% w/w) compared to the stratum corneum of skin (40% w/w), the resistance to penetration of the cornea is comparable to what is seen in previous research of penetration in skin tissue. Using low density polymer particles with a therapeutic agent payload, it is demonstrated that bulk material can be ballistically delivered to the central 1 cm² of the corneal epithelium in an even layer with high bioavailability of therapeutic compound.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.jmbbm.2020.104246DOIArticle
ORCID:
AuthorORCID
Laccetti, Benjamin0000-0002-0399-1204
Kornfield, Julia0000-0001-6746-8634
Additional Information:© 2020 Published by Elsevier. Received 10 July 2020, Revised 19 November 2020, Accepted 29 November 2020, Available online 5 December 2020. We would like to acknowledge Professor Alex Groisman for getting our group started with technology for ballistics research. Also, we would like to thank Professor Guruswamy Ravichandran for fruitful discussions regarding impact mechanics. We would like to thank Sakura Finetek for funding to complete this research. Also, we would like to thank The Jacobs Institute for Molecular Medicine for funding and the Rosen Center for Bioengineering. We would also like to thank the Caltech Biotechnology Leadership Program (a pre-doctoral program focusing on Micro/Nano medicine) for their support through NIH grant T32GM112592. Data availability statement: The data that support the findings of this study are available from the corresponding author upon request. CRediT authorship contribution statement: Benjamin Laccetti: Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing - original draft, Visualization. Julia Kornfield: Conceptualization, Writing - review & editing, Supervision, Project administration, Funding acquisition. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Group:Jacobs Institute for Molecular Engineering for Medicine, Rosen Bioengineering Center
Funders:
Funding AgencyGrant Number
Sakura FinetekUNSPECIFIED
Joseph J. Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIH Predoctoral FellowshipT32GM112592
Subject Keywords:Cornea; Drug-delivery; Keratoconus; Gelatin; Penetration
Record Number:CaltechAUTHORS:20201208-105038922
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201208-105038922
Official Citation:Benjamin Laccetti, Julia Kornfield, Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue, Journal of the Mechanical Behavior of Biomedical Materials, Volume 115, 2021, 104246, ISSN 1751-6161, https://doi.org/10.1016/j.jmbbm.2020.104246. (http://www.sciencedirect.com/science/article/pii/S1751616120307852)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106966
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Dec 2020 15:47
Last Modified:16 Dec 2020 19:18

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