An In Vivo Confocal Raman Study of the Delivery of Trans-Retinol to the Skin

Abstract

The purpose of this study is to monitor in vivo the delivery of trans-retinol into human skin. Delivery to real systems, such as skin, can be extremely difficult to execute and is problematic to confirm and measure. So far, methods for studying the delivery of compounds through the skin are mostly ex vivo and so inherently influence the skin and may not translate directly to the in vivo situation. Raman spectroscopy is uniquely placed to be able to measure biological processes in vivo, and this paper shows that the trans-retinol penetration into the skin can successfully be measured in vivo using this technique. This study measured the volar forearm of volunteers treated with 0.3% trans-retinol in propylene glycol (PG)/ethanol and 0.3% trans-retinol in caprylic/capric acid triglyceride (MYRITOL318), an oil found in skin creams. Solutions were applied and then confocal Raman depth profiles were obtained of the stratum corneum (SC) and into the viable epidermis (VE) up to 10 hours after treatment. Remarkable differences between a penetrating and a nonpenetrating solution can clearly be observed. Treating with trans-retinol in PG/ethanol results in trans-retinol penetrating through the SC and into the VE. Its penetration was also observed to be highly correlated with the depth of penetration of the PG, which is well known as an efficient penetration enhancer. In contrast, while treating with trans-retinol in MYRITOL318, trans-retinol hardly penetrates at all. For the first time, the penetration of trans-retinol has been monitored directly after application of solutions, in vivo without skin excision. Here, the effect of two different solutions on the delivery of trans-retinol into the skin was measured very effectively in vivo by Raman spectroscopy.

Skin Irritation and Sensitization: Mechanisms and New Approaches for Risk Assessment

“…SC barrier properties and transcutaneous penetration of different substances have recently been demonstrated by in vivo Raman microspectrometry [77,91,116] . However, one should keep in mind that the newly developed methods are at the dawn and time is needed to standardize the protocols and summarize the cumulated experience.…”

Confocal Raman Microscopy: Performance, Pitfalls, and Best Practice

“…Numerous workers have confirmed the benefits of using immersion objectives to depth profile complicated materials ranging from polymers and paper products to human skin. [29][30][31][32][33][34][35][36][37][38][39][40] As well as reducing the depth-scale compression, the oil has an additional beneficial effect of wetting out particle/air boundaries in porous, highly scattering particulate coatings, improving transparency and permitting confocal profiling of samples that would be opaque to a dry objective. 28 Nonetheless, a significant mismatch between the index of the coupling oil and the sample will result in a slight axial shift and distortion in the shape of individual layers, manifested by an attenuation that increases with depth.…”

How Confocal Is Confocal Raman Microspectroscopy on the Skin? Impact of Microscope Configuration and Sample Preparation on Penetration Depth Profiles

“…The increasing use of CRM to establish skin penetration profiles has led to an increasing variety of microscope configurations and sample preparation methods used therein (table 1) [3,4,13,14,15,16,17,18,19,20,21,22,23,24]. …”