#2-2. Effective delivery of hyaluronic acid

The oral formulation of HA has been researched in Japan since the 1980s. Currently, Prejunex imported by Iljo Pharmaceuticals has been introduced to the Korean market and is presented at medical symposia and conferences. Personally, I am very interested in the oral formulation as it was very popular in the Japanese population whose genetic makeup is very similar to the Koreans and it was also extensively studied. Moreover, it seemed very useful in the enlarging geriatric population where dry eye syndrome is often accompanied with degenerative arthritis^3-4.

The oral form that was used in previous studies was more often extracted from chicken comb than microbial fermentation. The oral form is small-molecule high-absorption HA in the 14kDa to 200kDa range. The molecular weight was usually within 100kDa. Ingested HA is degraded by hyaluronidase-releasing intestinal bacteria such as Staphylococcus aureus and Clostridium perfringens and delivered to the skin to help generation of new HA and fibroblast proliferation^-4

From 2001 to 2012, six studies conducted in Japan, China and Europe compared the efficacy of oral HA (randomized, double-blind, placebo-controlled study). Let me briefly summarize the results.¹⁰ the oral doses used ranged from 37.52mg to 240mg, of which 120mg (3 of 6) were the most common. Treatment period ranged from 4 to 12 weeks, and 6 weeks was the most common treatment period (3 of 6). The molecular weight ranged from 2.5kDa to 80kDa, showing that lower molecular weights were preferred.

The main effect seen was skin moisturization and the skin pH, TEWL, and clinical photographs were used for comparison. Effects generally appeared around 2 weeks after treatment and continued for 2 weeks after treatment completion. Considering the stratum corneum turnover cycle is 4 weeks, I think it is credible that improvements were seen 2 weeks both after treatment initiation and completion.

In the six studies, the molecular weight or the source of oral HA had no impact on efficacy.

1. Transdermal administration (nano-sized topical HA)

Image 2. Topical HA: Hyalogy Forlle’d.

Various topical HA products are entering the market, thanks to the recent advancement of nano technology. Transdermal drug delivery of hydrophilic macromolecule HA has become possible. In the past, topical HA was at molecular size of around 3000nm but intercellular space is only 15-50nm, which even falls to 6-10nm in the hyaline membrane. Due to these limitations, past topical HA products were thought to be not absorbed in the dermis. Therefore, mesotherapy.