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.
Highlights
Ophthalmic ultrasound as a research field started in 1956, when researchers Mundt and Hughes, using an ultrasonic reflectoscope, found that they could calculate the horizontal distance between ocular tissues based on sent ultrasound waves and received echoes in a single axis [1]
Due to the unique anatomy of the eye, i.e., the presence of the ocular barriers, the Microbubbles development of efficacious ocular therapeutics poses a major challenge in ophthalmology, In thisinsection, we summarize the studies that investigated the use some of ultrasound and microbubbles (USMB)
GFP-positive cells were localized in the ciliary muscle and the ciliary drug or gene delivery in the cornea be facilitated upon intracorneal injection of microbubbles.body
Summary
Ophthalmic ultrasound as a research field started in 1956, when researchers Mundt and Hughes, using an ultrasonic reflectoscope, found that they could calculate the horizontal distance between ocular tissues based on sent ultrasound waves and received echoes in a single axis (a technique known as A-mode ultrasonography) [1]. Microbubbles exposed to ultrasound waves undergo oscillations that induce various bioeffects on the surrounding structures These bioeffects can be exploited to improve the local administration of drugs and genes. Preclinical investigations of the therapeutic use of ultrasound and microbubbles (USMB) have been conducted in the field of ophthalmology, where there is a clear need for improved new delivery methods. The aim of this review is to provide an overview of the different therapeutic applications of USMB in ophthalmology (Figure 1). These can be divided into two distinct applications: (i) disruption of the blood–retina barrier and extravasation of drugs/genes that circulate in the bloodstream, and (ii) intracellular uptake of drugs/genes in various ocular cells. The structure of this review is as follows: Use first,of a brief introduction on the mechanisms
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