Influence of active Er-laser delivery on the optical properties of drug

Abstract

Laser drug delivery is perspective method which increase the speed of drug delivery. To increase the delivery efficiency of local pharmaceutical preparations, many methods are used including microporation. Laser microporation differs from other methods of microporation by minimal invasiveness and improved pharmacokinetics of the drug [1]. Drug delivery through microchannels into the biotissue can be passive or active, that is, can occur without or as a result of any external influence. With passive drug delivery, water-based preparations penetrate the microporated biotissue very slowly due to a high coefficient of surface tension. With active laser drug delivery, the laser-induced hydrodynamic processes increase the rate of drug penetration into biological tissues as a result of a generation of pressure waves [2]. Laser active drug delivery can be applied in the treatment of onychomycosis. The aim of our work was to study the features of active laser delivery of photosensitizers such as methylene blue, “Revixan” gel (Areal Ltd., Russia) and “Chloderm” (DPT Laboratory Ltd., USA) by action of Er:YLF laser radiation (wavelength 2810 nm) on the drug layer placed on the dorsal surface of the nail plate before microporation. All these photosensitizers are widely used for photodynamic therapy of fungal diseases.
The minimum number of laser pulses required for active Er-laser delivery of photosensitizers with different concentrations under the nail was determined. It has been shown that the penetration efficiency of water-based drugs is higher than that of gel-based drugs. In addition, it has been found that the effectiveness of active delivery depends on the concentration of the drug.
An important issue is the preservation of the drug properties after active laser delivery. It is known that laser radiation and photodynamic action can affect the optical properties of a drug. Analysis of the extinction spectrum of a drug before and after laser exposure makes it possible to assess the possibility and scale of these changes. Therefore, we investigated the effect of Er:YLF laser radiation and photodynamic light action (wavelength 656±10 nm) on photosensitizers analyzing their extinction spectra in the range of 400–900 nm. The changes in extinction spectra observed after Er:YLF laser drug delivery and PDT were associated with changes in conformation state of photosensitizers. The change in the intensity of characteristic bands in the extinction spectra and their shift were examined. These changes indicate conformational rearrangements in the photosensitizer molecules and changes in their functional characteristics. The Er:YLF laser radiation affects the shape of the extinction spectrum of an aqueous solution of methylene blue, which is associated with the transition of the dye from monomeric state to the dimeric state. It was found that after Er:YLF laser irradiation of chlorin-containing photosensitizers, their absorption band shifts to longer wavelengths, which may be associated with the transformation of drug molecules. In addition, the extinction coefficient of these photosensitizers increases, which may be due to an increase in drug concentration due to the evaporation of water (drug base). After PDT, a decrease in the extinction coefficient (bleaching) of photosensitizers associated with the destruction of molecules was observed.
1. Murdan S. Enhancing the nail permeability of topically applied drugs. Expert opinion on drug delivery. 2008;5(11):1267-1282.
2. Belikov AV, Skrypnik AV, Shatilova KV, Tuchin VV, Multi-beam laser-induced hydrodynamic shock waves used for delivery of microparticles and liquids in skin. Lasers in Surgery and Medicine. 2015;47(9):723–736.

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Anastasia Tavalinskaia
ITMO University
Russian Federation

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