Intrafollicular delivery of glucocorticoids using vaterite particles and optical monitoring of their degradation process

Abstract

Administration of therapeutic molecules via skin appendages has gained great scientific interest, especially concerning delivery to specific targeted regions and the reduction of systemic toxicity. This approach appears beneficial when creating topical formulations for glucocorticoids (GCS) to treat inflammatory skin diseases as allows one to improve their penetration through the stratum corneum and intradermal accumulation in the sites of GCS receptors. Low dermal bioavailability of GCS causes the need for repeated applications of conventional topical formulations that contributes to the development of skin atrophy. The GCS delivery into hair follicles opens up the possibility to localize and enhance its therapeutic effect, since a large number of GCS receptors are located in the outer root sheath of the follicle, as well as in the areas of the sebaceous glands and sweat ducts.
We report on a novel particulate system for GCS delivery to hair follicles based on the use of porous calcium carbonate carriers. Optical coherent tomography (OCT) was used to explore the potential of the GCS-loaded vaterite carriers to penetrate into hair follicles in vivo and to degrade there over time.
Effective intrafollicular accumulation of the carriers was demonstrated after their US-assisted topical application in vivo in rats. A high-frequency (1 MHz) ultrasound was used to facilitate the delivery of the GCS-loaded vaterite particles and provide a dense follicular filling. The obtained OCT images are presented in Fig. 1. The empty hair follicles are less scattering than the surrounding tissue, thus were clearly observed at the OCT images as dark inclined channels (Fig. 1 “before”). After the carriers’ application, the follicles appeared brighter that indicated their filling with the intensely reflecting vaterite carriers (Fig. 1 “after”), since the refractive indices of vaterite (n0 = 1.5500 and ne = 1.6553) are higher than those of dermis (n = 1.4). These results indicated that the designed GCS-loaded carriers successfully accumulated in skin targeting the pilosebaceous unit. That opens up a great perspective for the enhancement of therapeutic potential for the encapsulated glucocorticoid as the cells located in the outer root sheath, papillary matrix, and sebaceous glands represent important targets for its action.
Further monitoring of the experimental site using OCT revealed a tendency of a gradual degradation of the GCS-loaded carriers as the follicles became less and less scattering by time. These observations were in good agreement with the results obtained for the pure vaterite submicron carriers applied in rats in vivo, where SEM and CLSM investigation of the carrier degradation process demonstrated active dissolution/recrystallization of vaterite inside the hair follicles resulted in resorption of the bulk of the carriers whiting 168 h. Intrafollicular resorption of the carriers should lead to a lasting liberation of GCS.

The research was supported by RSF (№ 22-73-10194-П).


File with abstract

Speaker

Mariia Saveleva
Saratov State University
Russia

Discussion

Ask question