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Microbubble-assisted pLIFU enhances riboflavin delivery and corneal cross-linking in an in vivo rabbit keratoconus-like model.

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Τίτλος: Microbubble-assisted pLIFU enhances riboflavin delivery and corneal cross-linking in an in vivo rabbit keratoconus-like model.
Συγγραφείς: Wang Q; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Guo S; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Sun Y; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Wu Y; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Lin Z; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Wang T; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Chen X; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China., Su Q; Department of Oncology, Beijing Friendship Hospital, Capital Medical University. Beijing, China., Zheng Y; Department of Ophthalmology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Wu Y; Department of Cardiology, the First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China., Wang D; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China. Electronic address: wang.diya@xjtu.edu.cn., Wan M; Department of Biomedical Engineering, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Πηγή: Ultrasonics sonochemistry [Ultrason Sonochem] 2026 Oct; Vol. 133, pp. 108075. Date of Electronic Publication: 2026 Sep 23.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 9433356 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2828 (Electronic) Linking ISSN: 13504177 NLM ISO Abbreviation: Ultrason Sonochem Subsets: MEDLINE
Imprint Name(s): Publication: Amsterdam : Elsevier Science
Original Publication: Oxford : Butterworth Heinemann, c1994-
Ιατρικοί όροι (MeSH): Riboflavin*/therapeutic use , Riboflavin*/administration & dosage , Riboflavin*/pharmacology , Riboflavin*/metabolism , Keratoconus*/drug therapy , Keratoconus*/pathology , Keratoconus*/metabolism , Cornea*/drug effects , Cornea*/metabolism , Cornea*/pathology , Drug Delivery Systems*/methods , Microbubbles* , Ultrasonic Waves*, Collagen/metabolism ; Animals ; Rabbits ; Corneal Cross-Linking ; Disease Models, Animal
Περίληψη: Epithelium-off corneal collagen cross-linking (CXL) slows keratoconus progression but disrupts the epithelial barrier, whereas epithelium-on CXL is constrained by limited stromal riboflavin loading and insufficient evidence that physical delivery enhancement improves CXL outcomes in vivo keratoconus-like ectasia. Here, we developed microbubble-assisted pulsed low-intensity focused ultrasound (pLIFU) to enhance riboflavin transport through cavitation and evaluated its therapeutic effect in a collagenase-induced rabbit keratoconus-like model. Passive cavitation detection and temperature monitoring identified a treatment condition of 1 Hz pulse repetition frequency, 20 % duty cycle, 1.43 MPa focal-zone peak negative pressure, and 200 μl SonoVue solution, with maximum temperature rise limited to 1.5 °C. Hydrophone measurements showed low posterior-segment acoustic action, with a retinal-position mechanical index of approximately 0.076. Confocal fluorescence imaging showed that pLIFU with microbubbles increased peak stromal riboflavin fluorescence by 9.27 ± 2.16-fold (p < 0.0001) and effective penetration depth by 4.09-fold (p < 0.001) relative to control. In vivo, pLIFU-microbubble-enhanced CXL produced greater corneal flattening and a larger shear-wave-speed response than the US group. One month after treatment, central corneal curvature decreased by 45.85 ± 6.32 % and shear-wave speed (cs) increased by 52.50 ± 12.89 % relative to pretreatment in the USMB group. Short-term histology and inflammatory cytokine assays showed no sustained inflammatory elevation or overt retinal laminar disruption within the observation window. These findings support the early feasibility of pLIFU cavitation-enhanced riboflavin delivery as a physical augmentation strategy for epithelium-on CXL in keratoconus-like ectasia, with favourable short-term ocular tissue tolerance for the assessed endpoints; they do not establish non-inferiority to epithelium-off CXL or long-term safety and durability.
(Copyright © 2026. Published by Elsevier B.V.)
Competing Interests: Declaration of competing interest 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.
References: J Acoust Soc Am. 2016 Jan;139(1):204-14. (PMID: 26827018)
Sci Adv. 2024 Feb 9;10(6):eadk8426. (PMID: 38335289)
Pharmaceutics. 2023 Apr 11;15(4):. (PMID: 37111705)
Theranostics. 2020 Feb 10;10(7):2982-2999. (PMID: 32194850)
Invest Ophthalmol Vis Sci. 2014 Mar 28;55(3):1976-84. (PMID: 24519426)
Ophthalmology. 2017 Sep;124(9):1259-1270. (PMID: 28495149)
Ultrasonics. 2021 Sep;116:106478. (PMID: 34174743)
Ultrasound Med Biol. 2016 Mar;42(3):782-94. (PMID: 26674676)
Acta Ophthalmol. 2009 Feb;87(1):48-51. (PMID: 18547280)
IEEE Trans Biomed Eng. 2018 Nov 20;:. (PMID: 30475706)
J Colloid Interface Sci. 2024 Jun 15;664:533-538. (PMID: 38484521)
J Refract Surg. 2010 Apr;26(4):259-71. (PMID: 20415322)
Cont Lens Anterior Eye. 2022 Jun;45(3):101559. (PMID: 34991971)
IEEE Trans Biomed Eng. 2021 Sep;68(9):2637-2644. (PMID: 33306463)
Cells. 2023 Nov 22;12(23):. (PMID: 38067109)
Ultrasound Med Biol. 1992;18(9):731-810. (PMID: 1362301)
Ultrasound Med Biol. 2002 Jun;28(6):823-9. (PMID: 12113795)
Sci Rep. 2020 Jul 31;10(1):12983. (PMID: 32737363)
Am J Ophthalmol. 2003 May;135(5):620-7. (PMID: 12719068)
PLoS One. 2012;7(8):e42754. (PMID: 22912733)
Theranostics. 2023 Jun 19;13(11):3582-3638. (PMID: 37441595)
Expert Opin Drug Deliv. 2017 Apr;14(4):539-550. (PMID: 27310925)
JAMA Ophthalmol. 2016 Feb;134(2):167-73. (PMID: 26633035)
Transl Vis Sci Technol. 2024 Feb 1;13(2):15. (PMID: 38376862)
Ultrason Sonochem. 2017 Mar;35(Pt A):176-184. (PMID: 27707644)
Research (Wash D C). 2023 Aug 15;6:0200. (PMID: 37588619)
Acta Ophthalmol. 2016 Nov;94(7):675-678. (PMID: 27213687)
Ultrason Sonochem. 2020 Oct;67:105096. (PMID: 32278246)
Med Phys. 2015 Oct;42(10):5604-15. (PMID: 26429235)
ACS Sens. 2024 May 24;9(5):2356-2363. (PMID: 38752383)
Ultrason Sonochem. 2019 Apr;52:512-521. (PMID: 30642801)
Research (Wash D C). 2023 Sep 01;6:0221. (PMID: 39830009)
Invest Ophthalmol Vis Sci. 2013 Aug 28;54(8):5908-12. (PMID: 23920369)
Ultrason Imaging. 2019 Sep;41(5):251-270. (PMID: 31271117)
J Cataract Refract Surg. 2009 Mar;35(3):540-6. (PMID: 19251149)
BMC Ophthalmol. 2018 Apr 13;18(1):94. (PMID: 29653563)
Invest Ophthalmol Vis Sci. 2006 Feb;47(2):558-64. (PMID: 16431951)
IEEE Trans Med Imaging. 2009 Dec;28(12):1881-93. (PMID: 19423431)
Biomed Opt Express. 2022 Apr 05;13(5):2644-2654. (PMID: 35774330)
IEEE Trans Biomed Eng. 2022 Nov;69(11):3449-3459. (PMID: 35476579)
Nat Commun. 2024 Sep 13;15(1):8021. (PMID: 39271721)
Am J Ophthalmol. 2014 Mar;157(3):623-30.e1. (PMID: 24321474)
Ultrasound Med Biol. 2021 Aug;47(8):2296-2309. (PMID: 33985825)
J Cataract Refract Surg. 2015 Jan;41(1):41-6. (PMID: 25532633)
Pharmaceutics. 2023 Jul 06;15(7):. (PMID: 37514082)
Ultrason Sonochem. 2023 Mar;94:106346. (PMID: 36870921)
Invest Ophthalmol Vis Sci. 2012 Aug 31;53(9):5948-54. (PMID: 22871840)
J R Soc Interface. 2012 Nov 7;9(76):3081-93. (PMID: 22764133)
Exp Eye Res. 2007 Dec;85(6):741-8. (PMID: 17889849)
Transl Vis Sci Technol. 2023 Mar 1;12(3):15. (PMID: 36930138)
J Control Release. 2020 Oct 10;326:75-90. (PMID: 32554041)
Research (Wash D C). 2023;6:0048. (PMID: 37040522)
J Ultrasound Med. 2024 Jan;43(1):127-136. (PMID: 37842972)
IEEE Trans Ultrason Ferroelectr Freq Control. 2011 Oct;58(10):2032-5. (PMID: 21989866)
J Acoust Soc Am. 2023 Apr 1;153(4):2324. (PMID: 37092939)
Opt Lett. 2012 Aug 15;37(16):3312-4. (PMID: 23381241)
Med Hypothesis Discov Innov Ophthalmol. 2016 Winter;5(4):125-131. (PMID: 28293660)
Nat Commun. 2018 May 14;9(1):1864. (PMID: 29760442)
Indian J Ophthalmol. 2018 Feb;66(2):190-194. (PMID: 29380756)
Bioeng Transl Med. 2022 Nov 25;8(2):e10442. (PMID: 36925678)
Bioengineering (Basel). 2023 Apr 16;10(4):. (PMID: 37106666)
Research (Wash D C). 2024 Oct 14;7:0504. (PMID: 39403258)
Biomed Res Int. 2017;2017:3684971. (PMID: 29104870)
J Control Release. 2018 Feb 28;272:169-181. (PMID: 29305924)
Curr Eye Res. 2004 Jul;29(1):35-40. (PMID: 15370365)
Cornea. 2024 Apr 1;43(4):437-442. (PMID: 37851565)
J Control Release. 2022 Sep;349:388-400. (PMID: 35787912)
Eye Vis (Lond). 2021 Sep 1;8(1):34. (PMID: 34565473)
Ophthalmology. 2021 Aug;128(8):1150-1160. (PMID: 33383093)
Am J Ophthalmol. 2015 May;159(5):821-8.e3. (PMID: 25703475)
IEEE Trans Biomed Eng. 2023 Oct;70(10):2874-2885. (PMID: 37159313)
J Nanobiotechnology. 2024 Sep 28;22(1):588. (PMID: 39342257)
AAPS J. 2010 Sep;12(3):348-60. (PMID: 20437123)
Contributed Indexing: Keywords: Acoustic cavitation; Corneal collagen cross-linking; Keratoconus; Microbubble cavitation; Pulsed low-intensity focused ultrasound; Riboflavin delivery
Substance Nomenclature: TLM2976OFR (Riboflavin)
9007-34-5 (Collagen)
Entry Date(s): Date Created: 20260925 Date Completed: 20261005 Latest Revision: 20261007
Update Code: 20261007
PubMed Central ID: PMC13635697
DOI: 10.1016/j.ultsonch.2026.108075
PMID: 42790152
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1873-2828
DOI:10.1016/j.ultsonch.2026.108075