Eyedrops, jets and tattoos: Understanding the fluid dynamics of ophthalmic and transdermal drug delivery

Date

2023-12

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Abstract

Drug delivery continues to be an aspect of medicine with vast scientific interest due to the need for more user-friendly and minimally invasive therapeutic modalities. This need has led to the development of several alternatives to conventional drug administration techniques with the aim of alleviating patient discomfort and improving bioavailability. However, these techniques have their own drawbacks, such as restricted drug dosage, inefficient delivery, a tedious manufacturing process, high costs, and human tolerance. This thesis examines the fluid dynamics of ophthalmic, and transdermal drug delivery, with a particular emphasis on the effect of parameters related to delivery devices and the role of fluid properties and rheology. We leverage high-speed imaging and digital image processing via in vitro and ex vivo experiments to characterize drug deposition inside skin and spreading behavior on eyeball replicas. We discuss potential strategies to enhance the effectiveness of drug delivery to the eyes and skin, as well as the challenges that may be encountered. We also point out the potential solutions to these issues. In ophthalmic drug delivery, we investigate the fluid dynamics involved in the spreading of eye drops, with the goal of reducing the amount of medication wasted in Front-of-the-Eye (FOTE) delivery. In particular, we investigate the influence of impact speed, fluid rheology, and prewetting on droplet spreading across a broad parameter space ReO(101−104) and WeO(101−102). In addition, we present our findings on the role of the tear film and how it facilitates, yet sometimes limits the spreading of eye drops. We also compare the agreement of spreading dynamics of drops of different fluids on the eye replica using existing scaling laws for curved substrates. Furthermore, we explore the possibility of the application of discrete jetting in drug deposition on the eye. We fins that the area of coverage and the force of impact are limited to a small area because of the inherent nature of focused jets compared to that of a droplet hitting the same substrate. The second focus of this thesis is on transdermal drug delivery, which includes our work on understanding the fluid dynamics of drug infusion into the skin by tattooing and jet injections. In drug delivery by tattooing, we studied drug deposition in transparent hydrogels used as in vitro proxies in addition to ex vivo studies in pork skin. We investigated the effect of parameters related to the tattoo machine (needle frequency, fO(101−102)) and the properties of fluids (viscosity, μ) injected on the drug deposition process and the amount deposited. Furthermore, we characterized the hydrodynamics of a spring-powered needle-free jet injector with variation in spring constant, volume delivered, and fluid properties. We then quantified the performance of this jet injector in terms of injection depth within human skin. The jet injector can target different regions under the skin up to the muscle layer depending on the spring force, whereas tattooing is limited to the epidermis and dermis layer. Our work provides a guide to future studies on these techniques for conducting in vivo and human tolerance studies.


Embargo status: Restricted until 01/2027. To request the author grant access, click on the PDF link to the left.

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Keywords

Fluid dynamics, drug delivery, needle-free

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