Microneedle Arrays Permit Enhanced Intradermal Delivery of a Preformed Photosensitizer

Abstract

Silicon microneedle (MN) arrays were used to puncture excised murine and porcine skin in vitro and transdermal and intradermal delivery of meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP) investigated using topical application of a bioadhesive patch containing 19 mg TMP cm . Animal studies, using nude mice, were then conducted to investigate the in vivo performance of the bioadhesive patch following MN puncture of skin. MN puncture significantly enhanced both intradermal and transdermal delivery of TMP in vitro, though the total amounts of drug delivered (25.22% into porcine skin and 0.07% across murine skin) were still quite small in each case. Notwithstanding this, in vivo experiments showed that MN puncture was capable of permitting a prolonged increase in TMP fluorescence at the site of application. Importantly, fluorescence was negligible at distant sites, meaning systemic delivery of the drug was not sufficient to induce TMP accumulation other than at the application site. In this study we have conclusively demonstrated proof of principle; MN puncture allows true intradermal delivery of a preformed photosensitizer in animal skin models in vitro and in vivo. Importantly, transdermal delivery was much reduced in each case. Increasing MN density would allow increased amounts of photosensitizer to be delivered. However, as MNs create aqueous pores in the stratum corneum, a preformed photosensitizer must possess at least some degree of water solubility in order to permit enhanced intradermal delivery in this way. We believe that use of MN array technology in this way has the potential to significantly improve topical photodynamic therapy of skin tumors.

Microneedles in Clinical Practice–An Exploratory Study Into the Opinions of Healthcare Professionals and the Public

“…Microneedles are designed to specific dimensions to facilitate piercing of the outer barrier layer of skin, the stratum corneum, to enable drug and vaccine delivery, without impinging on the underlying pain receptors and blood vessels. Since the first demonstration that microneedles were effective in facilitating the delivery of calcein across the skin (1), there has been widespread academic and commercial interest in their development, resulting in extensive research into suitable fabrication methodologies (2)(3)(4)(5)(6)(7) and potential pharmaceutical and pharmacological applications (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Those intimately involved in the scientific development and testing of microneedles perceive that this new delivery method will confer many advantages compared with conventional dosage forms.…”

Can surgical site infections be treated by photodynamic therapy?

“…For instance it may be necessary to use specialized surfactants [5] and penetrating agents [6] to help the PS pass into and through the infected tissue. Alternatively physical/mechanical means such as microneedle arrays [7], high-pressure sprays (needle-free injection systems) [8], iontophoresis [9], or fractional laser ablation [10] may be able to increase the penetration of the PS into the infected tissue.…”

Photodynamic photorejuvenation of the face with a combination of microneedling, red light, and broadband pulsed light

“…Shallow penetration of ALA does occur with time; however, short incubation times, focal areas of epidermal hyperkeratosis, the presence of skin surface sebum and topical cosmetics products can lead to non-uniform absorption and ultimately compromise results. To overcome these obstacles, various strategies have been employed to enhance topical penetration of ALA, including prolonged incubation times, curettage, use of chemical penetration enhancers, iontophoresis, microneedling, and microdermabrasion [8,9]. These strategies are sometimes impractical to employ in a practice with high patient volume because they can be too time consuming (long incubation times, ionophoresis, microdermabrasion) or because they may be potentially too destructive (curettage) to the skin.…”

“…These strategies are sometimes impractical to employ in a practice with high patient volume because they can be too time consuming (long incubation times, ionophoresis, microdermabrasion) or because they may be potentially too destructive (curettage) to the skin. Indeed, longer incubation times can result in more pain during treatment, presumably due to increase penetration and uptake at nerve endings [8].…”