Abstract

Restoring hyaluronic acid (HA) content is important for maintaining the function of photo-aged skin. This study aimed to evaluate the passive delivery into skin of HA nanoparticles formed by the polyion complex method. Nanoparticles were prepared by mixing and stirring anionic HA with a cationic polymer, protamine, at the charge ratio 55:45. The permeation of fluorescently-labelled HA nanoparticles (HANP) or free HA through hairless mouse skin was characterized in vitro. HANP or free HA was applied to ultraviolet (UV)-irradiated mice in vivo, and their transepidermal water loss (TEWL) was measured after 4 days. HA that had been delivered into skin was separated and characterized by molecular sieve chromatography. HANP were able to deliver HA into the dermis both in vitro and in vivo, whereas free HA penetrated no further than the stratum corneum. Following HANP application, HA within the skin was present in the form of free HA rather than nanoparticles. When applied in vivo, HANP significantly reduced the TEWL caused by UV irradiation. Thus, although free HA does not penetrate into the skin by passive diffusion, HA can be effectively delivered by nanoparticles. HA is then released from the nanoparticles and can contribute to barrier recovery following UV irradiation.

Highlights

  • The barrier function of skin is principally attributed to the stratum corneum

  • We have shown that polymeric hyaluronic acid (HA) can be formulated into nanoparticles using the polyion complex method

  • Free HA cannot be delivered into the skin, we found the application of an emulsified preparation of HA nanoparticles (HANP) led to the passive diffusion of HA into the skin

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Summary

Introduction

The barrier function of skin is principally attributed to the stratum corneum. Only small molecules, usually less than 500 Da, and lipophilic compounds can penetrate the skin barrier[1]. Many researchers want to deliver HA to deeper skin. HA injection has been widely used for delivery into the skin This method is not good as it is noninvasive It has been reported the HA can be delivered into the skin by micro-needles and iontophoresis. The solid-in-oil (S/O) technique has been used to deliver high molecular weight compounds into the skin[11]. There are few reports that it is able to deliver materials to the deeper skin, where HA is found. There are several reports on hyaluronic acid nanoparticles. There is no report using hyaluronic acid nanoparticles as a transdermal absorption enhancement. The penetration into the skin of these HA nanoparticles (HANP) was compared in vivo and in vitro with non-nanoparticulate HA. The ability of the HANP to reduce UV-induced skin damage in mice was evaluated

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