Optimized skin optical clearing for optical coherence tomography monitoring of encapsulated drug delivery through the hair follicles

Abstract

Hair follicles (HF) represent a drug delivery reservoir for improved treatment of skin disorders. Although various particulate systems play an important role in HF‐targeting, their optical monitoring in skin is challenging due to strong light scattering. Optical clearing is an effective approach allowing the increasing of particle detection depth in skin. The enhancement of optical probing depth (OPD) and optical detection depth (ODD) of particle localization using optical coherence tomography (OCT) was evaluated under application of various optical clearing agents (OCAs) together with skin permeability enhancers ex vivo in rats. Efficient OPD increasing was demonstrated for all investigated OCAs. However, skin dehydration under action of hyperosmotic agents led to the worsening of OCT‐contrast in dermis decreasing the ODD. Lipophilic agents provided optical clearing of epidermis without its dehydration. The highest ODD was obtained at application of a PEG‐400/oleic acid mixture. This OCA was tested in vivo showing beneficial ODD and OPD enhancement.

Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?

“…Arrow in E denotes a hair follicle. BV: blood vessel, HF: hair follicle, SbG: sebaceous gland, SwG: sweat gland, ( B ) from [ 172 ], ( C ) from [ 170 ], ( E ) from [ 173 ].…”

“…Currently, only few groups applied OCT to track the permeation of exogenously added agents through the skin. In this context, OCT was used to follow nanoparticle delivery through HFs [ 173 , 180 ] and epidermis [ 181 ]. OCT was also used to track glucose diffusion across the skin of rhesus monkeys [ 182 ].…”

Biomedical Applications of Tissue Clearing and Three-Dimensional Imaging in Health and Disease

“…Skin can be cleared using agents such as sucrose, fructose, PEG-400 ( Zaytsev et al., 2020 ), PEG-300, salicylic acid ( Zhao et al., 2016 ), glycerol ( Zhong et al., 2010 ), or glucose solutions. These agents are commonly known as SOCAs (skin optical clearing agents) and generally adjust skin refractive indexes and induce packaging of scatterers such as collagen fibers ( Tuchina et al., 2019 ) by dehydration-driven reduction of skin thickness ( Wen et al., 2010 ).…”

“…These agents are commonly known as SOCAs (skin optical clearing agents) and generally adjust skin refractive indexes and induce packaging of scatterers such as collagen fibers ( Tuchina et al., 2019 ) by dehydration-driven reduction of skin thickness ( Wen et al., 2010 ). Several penetration enhancers are widely used to facilitate their diffusion and improve their clearing power; they can be classified into chemical penetration enhancers such as propylene glycol, DMSO ( Zaytsev et al., 2020 ), ethanol ( Zaytsev et al., 2020 ), azone ( Zhao et al., 2016 ), dimethyl sulfoxide ( Genina et al, 2020 ), oleic acid ( Zaytsev et al., 2020 ), and thiazone ( Zaytsev et al., 2020 ) (the last four ones achieve penetration enhancement by dissolving Stratum Corneum lipids) ( Zaytsev et al., 2020 ), and physical penetration enhancers, such as ultrasounds (sonophoresis) ( Genina et al, 2020 ), microneedles ( Yoon et al., 2010 ), lasers (FLMA, fractional laser microablation) ( Genina et al., 2020a ), pneumatic pressure ( Damestani et al., 2014 ), heat ( Damestani et al., 2014 ), or abrasive instruments (microdermabrasion) ( Genina et al, 2020 ). Different combinations of penetration enhancers have been applied to improve the efficacy of several clearing agents.…”

Optical Clearing of Human Skin Using Polyethylene Glycols

“…These difficulties are overcome by introducing biocompatible molecular agents into the tissue, which contribute, to some extent, to its optical clearing [2][3][4]. Quite a lot of works was devoted to experimental studies of the optical clearing of various types of tissues in vitro and in vivo [5][6][7][8][9][10][11] that indicates the importance of the problem. Mathematical models of light propagation in strongly scattering tissues with absorption are discussed in Ref.…”