Optical Drilling of the Human Nail Plate to Facilitate Transungual Drug Delivery

Simon Vanstone

Research output: ThesisDoctoral Thesis

Abstract

The nail plate is a thick, tightly bound structure that protects the underlying nail bed from water loss, physical abrasion and infections. Despite its barrier properties, organisms are capable of traversing across and around the plate causing infection to the nail unit. Nail disease represents a time and cost intensive problem for the healthcare industry, with current topical and systemic treatment methods failing to stop the rise in incidence. Physical poration of the nail plate is discussed here with the first use of a femtosecond pulsed, fibre optic delivered, visible-light laser for drilling.
Optical, Scanning Electron (SEM) and Atomic Force (AFM) microscopies were used to characterise the physical appearance of the nail plate before drilling. In addition, Fourier Transform Infrared (FTIR) and Raman spectroscopies were employed to investigate variation in the chemical structure of the nail plate across its thickness.
Poration of the nail plate was facilitated using a dye to increase absorption of the laser radiation. Pores were drilled to various depths and widths by varying the amplitude of light pulses and exposure time. Incorporation of an optical chopper into the setup reduced thermal damage to the surrounding nail tissue. The geometry of pores, and the damage to the tissue surrounding them, was characterised with optical, electron and confocal microscopies.
A novel technique to measure thermal damage surrounding the pore was developed. An empirical relationship between the Raman scattering and the temperature was established for nail pieces heat-treated at specific temperatures. This relationship was used to create temperature maps across porated areas. It was revealed the centre of pores were drilled by plasma-mediated poration, whilst thermal effects were responsible for removing material around the edges and damage to the remaining tissue.
Verification of drilling as a suitable technique to reduce the resistance of the nail to topical delivery, was demonstrated with the delivery of caffeine across nail samples. Poration through the entirety of the plate effectively circumvented the barrier provided by an intact, untreated sample. Partial poration reduced the lag time for diffusion across the plate thus speeding up the drug delivery process.
Original languageEnglish
QualificationPh.D.
Awarding Institution
  • University of Bath
Supervisors/Advisors
  • Gordeev, Sergey, Supervisor
  • Guy, Richard, Supervisor
Date of Award26 Sep 2017
StatePublished - May 2017

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drilling
delivery
damage
porosity
infectious diseases
drugs
water loss
caffeine
electric choppers
abrasion
organisms
temperature
temperature effects
beds
fiber optics
electrons
time lag
Raman spectroscopy
incidence
dyes

Cite this

Optical Drilling of the Human Nail Plate to Facilitate Transungual Drug Delivery. / Vanstone, Simon.

2017. 149 p.

Research output: ThesisDoctoral Thesis

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N2 - The nail plate is a thick, tightly bound structure that protects the underlying nail bed from water loss, physical abrasion and infections. Despite its barrier properties, organisms are capable of traversing across and around the plate causing infection to the nail unit. Nail disease represents a time and cost intensive problem for the healthcare industry, with current topical and systemic treatment methods failing to stop the rise in incidence. Physical poration of the nail plate is discussed here with the first use of a femtosecond pulsed, fibre optic delivered, visible-light laser for drilling.Optical, Scanning Electron (SEM) and Atomic Force (AFM) microscopies were used to characterise the physical appearance of the nail plate before drilling. In addition, Fourier Transform Infrared (FTIR) and Raman spectroscopies were employed to investigate variation in the chemical structure of the nail plate across its thickness.Poration of the nail plate was facilitated using a dye to increase absorption of the laser radiation. Pores were drilled to various depths and widths by varying the amplitude of light pulses and exposure time. Incorporation of an optical chopper into the setup reduced thermal damage to the surrounding nail tissue. The geometry of pores, and the damage to the tissue surrounding them, was characterised with optical, electron and confocal microscopies.A novel technique to measure thermal damage surrounding the pore was developed. An empirical relationship between the Raman scattering and the temperature was established for nail pieces heat-treated at specific temperatures. This relationship was used to create temperature maps across porated areas. It was revealed the centre of pores were drilled by plasma-mediated poration, whilst thermal effects were responsible for removing material around the edges and damage to the remaining tissue.Verification of drilling as a suitable technique to reduce the resistance of the nail to topical delivery, was demonstrated with the delivery of caffeine across nail samples. Poration through the entirety of the plate effectively circumvented the barrier provided by an intact, untreated sample. Partial poration reduced the lag time for diffusion across the plate thus speeding up the drug delivery process.

AB - The nail plate is a thick, tightly bound structure that protects the underlying nail bed from water loss, physical abrasion and infections. Despite its barrier properties, organisms are capable of traversing across and around the plate causing infection to the nail unit. Nail disease represents a time and cost intensive problem for the healthcare industry, with current topical and systemic treatment methods failing to stop the rise in incidence. Physical poration of the nail plate is discussed here with the first use of a femtosecond pulsed, fibre optic delivered, visible-light laser for drilling.Optical, Scanning Electron (SEM) and Atomic Force (AFM) microscopies were used to characterise the physical appearance of the nail plate before drilling. In addition, Fourier Transform Infrared (FTIR) and Raman spectroscopies were employed to investigate variation in the chemical structure of the nail plate across its thickness.Poration of the nail plate was facilitated using a dye to increase absorption of the laser radiation. Pores were drilled to various depths and widths by varying the amplitude of light pulses and exposure time. Incorporation of an optical chopper into the setup reduced thermal damage to the surrounding nail tissue. The geometry of pores, and the damage to the tissue surrounding them, was characterised with optical, electron and confocal microscopies.A novel technique to measure thermal damage surrounding the pore was developed. An empirical relationship between the Raman scattering and the temperature was established for nail pieces heat-treated at specific temperatures. This relationship was used to create temperature maps across porated areas. It was revealed the centre of pores were drilled by plasma-mediated poration, whilst thermal effects were responsible for removing material around the edges and damage to the remaining tissue.Verification of drilling as a suitable technique to reduce the resistance of the nail to topical delivery, was demonstrated with the delivery of caffeine across nail samples. Poration through the entirety of the plate effectively circumvented the barrier provided by an intact, untreated sample. Partial poration reduced the lag time for diffusion across the plate thus speeding up the drug delivery process.

M3 - Doctoral Thesis

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