Ultrasound and Microbubbles for the Treatment of Ocular Diseases: From Preclinical Research Towards Clinical Application

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Nov 27

PMID 34834196

Citations 12

Authors

Charis Rousou

Carl C L Schuurmans

Arto Urtti

Enrico Mastrobattista

Gert Storm

Chrit Moonen

Kai Kaarniranta

Roel Deckers

Affiliations

Soon will be listed here.

Abstract

The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood-retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed.

Citing Articles

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References

Mohamed Q, Gillies M, Wong T . Management of diabetic retinopathy: a systematic review. JAMA. 2007; 298(8):902-16. DOI: 10.1001/jama.298.8.902. View

Walia A, Yang J, Huang Y, Rosenblatt M, Chang J, Azar D . Endostatin's emerging roles in angiogenesis, lymphangiogenesis, disease, and clinical applications. Biochim Biophys Acta. 2015; 1850(12):2422-38. PMC: 4624607. DOI: 10.1016/j.bbagen.2015.09.007. View

Del Amo E, Rimpela A, Heikkinen E, Kari O, Ramsay E, Lajunen T . Pharmacokinetic aspects of retinal drug delivery. Prog Retin Eye Res. 2016; 57:134-185. DOI: 10.1016/j.preteyeres.2016.12.001. View

Giblin M, Shields J, Shields C, Eagle Jr R . Primary eyelid malignant melanoma associated with primary conjunctival malignant melanoma. Aust N Z J Ophthalmol. 1988; 16(2):127-31. DOI: 10.1111/j.1442-9071.1988.tb01261.x. View

Li W, Liu S, Ren J, Xiong H, Yan X, Wang Z . Gene transfection to retinal ganglion cells mediated by ultrasound microbubbles in vitro. Acad Radiol. 2009; 16(9):1086-94. DOI: 10.1016/j.acra.2009.03.019. View

Gordon Y . The evolution of antiviral therapy for external ocular viral infections over twenty-five years. Cornea. 2000; 19(5):673-80. DOI: 10.1097/00003226-200009000-00012. View

Belcik J, Mott B, Xie A, Zhao Y, Kim S, Lindner N . Augmentation of limb perfusion and reversal of tissue ischemia produced by ultrasound-mediated microbubble cavitation. Circ Cardiovasc Imaging. 2015; 8(4). PMC: 4384163. DOI: 10.1161/CIRCIMAGING.114.002979. View

MacCarthy A, Birch J, Draper G, Hungerford J, Kingston J, Kroll M . Retinoblastoma: treatment and survival in Great Britain 1963 to 2002. Br J Ophthalmol. 2008; 93(1):38-9. DOI: 10.1136/bjo.2008.139626. View

Aptel F, Tadjine M, Rouland J . Efficacy and Safety of Repeated Ultrasound Cycloplasty Procedures in Patients With Early or Delayed Failure After a First Procedure. J Glaucoma. 2019; 29(1):24-30. DOI: 10.1097/IJG.0000000000001400. View

10.

Stitt A, Curtis T, Chen M, Medina R, Mckay G, Jenkins A . The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2015; 51:156-86. DOI: 10.1016/j.preteyeres.2015.08.001. View

11.

Xu Y, Xie Z, Zhou Y, Zhou X, Li P, Wang Z . Experimental endostatin-GFP gene transfection into human retinal vascular endothelial cells using ultrasound-targeted cationic microbubble destruction. Mol Vis. 2015; 21:930-8. PMC: 4548789. View

12.

. WFUMB Symposium on Safety and Standardisation in Medical Ultrasound. Issues and Recommendations Regarding Thermal Mechanisms for Biological Effects of Ultrasound. Hornbaek, Denmark, 30 August-1 September 1991. Ultrasound Med Biol. 1992; 18(9):731-810. View

13.

Kendall C, Prager T, Cheng H, Gombos D, Tang R, Schiffman J . Diagnostic Ophthalmic Ultrasound for Radiologists. Neuroimaging Clin N Am. 2015; 25(3):327-65. DOI: 10.1016/j.nic.2015.05.001. View

14.

Shen X, Huang L, Ma D, Zhao J, Xie Y, Li Q . Ultrasound Microbubbles Enhance the Neuroprotective Effect of Mouse Nerve Growth Factor on Intraocular Hypertension-Induced Neuroretina Damage in Rabbits. J Ophthalmol. 2016; 2016:4235923. PMC: 5138486. DOI: 10.1155/2016/4235923. View

15.

Postema M, van Wamel A, Ten Cate F, de Jong N . High-speed photography during ultrasound illustrates potential therapeutic applications of microbubbles. Med Phys. 2006; 32(12):3707-11. DOI: 10.1118/1.2133718. View

16.

Culp W, Porter T, Xie F, Goertzen T, McCowan T, Vonk B . Microbubble potentiated ultrasound as a method of declotting thrombosed dialysis grafts: experimental study in dogs. Cardiovasc Intervent Radiol. 2002; 24(6):407-12. DOI: 10.1007/s00270-001-0052-4. View

17.

Park J, Zhang Y, Vykhodtseva N, Akula J, McDannold N . Targeted and reversible blood-retinal barrier disruption via focused ultrasound and microbubbles. PLoS One. 2012; 7(8):e42754. PMC: 3418291. DOI: 10.1371/journal.pone.0042754. View

18.

Vo Kim S, Fajnkuchen F, Sarda V, Qu-Knafo L, Bodaghi B, Giocanti-Auregan A . Sustained intraocular pressure elevation in eyes treated with intravitreal injections of anti-vascular endothelial growth factor for diabetic macular edema in a real-life setting. Graefes Arch Clin Exp Ophthalmol. 2017; 255(11):2165-2171. DOI: 10.1007/s00417-017-3782-y. View

19.

Lafond M, Aptel F, Mestas J, Lafon C . Ultrasound-mediated ocular delivery of therapeutic agents: a review. Expert Opin Drug Deliv. 2016; 14(4):539-550. DOI: 10.1080/17425247.2016.1198766. View

20.

Li H, Zheng X, Wang H, Li F, Wu Y, Du L . Ultrasound-targeted microbubble destruction enhances AAV-mediated gene transfection in human RPE cells in vitro and rat retina in vivo. Gene Ther. 2009; 16(9):1146-53. DOI: 10.1038/gt.2009.84. View