Absorption of Hyaluronan Applied to the Surface of Intact Skin

Abstract

Hyaluronan has recently been introduced as a vehicle for topical application of drugs to the skin. We sought to determine whether hyaluronan acts solely as a hydrophilic reservoir on the surface of intact skin or might partly penetrate it. Drug-free hyaluronan gels were applied to the intact skin of hairless mice and human forearm in situ, with and without [3H] hyaluronan. [3H]hyaluronan was shown by autoradiography to disseminate through all layers of intact skin in mouse and human, reaching the dermis within 30 min of application in mice. Cellular uptake of [3H]hyaluronan was observed in the deeper layers of epidermis, dermis, and in lymphatic endothelium. Absorption through skin was confirmed in mice by chromatographic analysis of blood, urine, and extracts from skin and liver, which identified 3H as intact hyaluronan and its metabolites, free acetate and water. Hyaluronan absorption was similarly demonstrated without polyethylene glycol, which is usually included in the topical formulation. [3H]hyaluronan absorption was not restricted to its smaller polymers as demonstrated by the recovery of polymers of (360-400 kDa) from both blood and skin. This finding suggests that its passage through epidermis does not rely on passive diffusion but may be facilitated by active transport. This study establishes that hyaluronan is absorbed from the surface of the skin and passes rapidly through epidermis, which may allow associated drugs to be carried in relatively high concentration at least as far as the deeper layers of the dermis.

Early experimental results of using a novel delivery carrier, hyaluronan-phosphatidylethanolamine (HA-PE), which may allow simple bladder instillation of botulinum toxin A as effectively as direct detrusor muscle injection

“…Small amounts of unmodified HA can cross epidermal layers, likely via its ability to insert into HA coats (24,25). However, most (> 98%) of the unmodified HA binds only to the skin surface, where it can act as a reservoir for slow-release drugs.…”

“…Procedurally, BTX-A injections are performed via cystoscopy and involve its injection directly into bladder muscle at multiple sites (e.g., [20][21][22][23][24][25][26][27][28][29][30], except usually the trigone.…”

Tolerability and hydrating effects of an anti-aging gynaecological collagen cream in women in menopause

“…the collagen neosynthesis, and to enhance the dermal metabolism [13,14]. The percutaneous absorption of hyaluronic acid was proven when applied with topical preparation to the intact skin though the strongly hydrophilic nature of the compound [15]. Vitamins A, C, E and B3 contribute to the anti-aging effect of many topical products.…”

Rheological Study of Binary Gels with Carbopol UltrezTM 10 and Hyaluronic Acid

“…Specifically, recent studies have propitiated its use in the development of new pharmaceutical dosage delivery forms. [13][14][15] One of the most important technical considerations in the galenic development of gelled water soluble bases designed specifically for topical use is the exhaustive rheological characterization of the systems studied and optimization of the rheological parameters related directly to application and topical delivery. Increased interest in these polymers for elaboration of cosmetic and pharmaceutical formulations justifies a complete rheological study of these gelled topical forms.…”