Permeation Enhancement of Ascorbic Acid by Self-Dissolving Micropile Array Tip through Rat Skin

Abstract

Ascorbic acid (AA, vitamin C) is a hydrophilic vitamin that cannot be produced endogenously in rats and primates including human and is widely used for the protection of the aging of the skin due to the exposure to the UV light and for the acceleration of the synthesis of collagen in the skin. [1][2][3][4] AA was shown to be absorbed from the gastrointestinal tract by an active transport system, though limited amount of AA was transported by this system. 5) In addition, after AA was absorbed, AA was rapidly eliminated from the body by the oxidative metabolism through both enzymatic and nonenzymatic processes.2) Therefore, even if we intake excess amount of AA, sufficient amount of AA is not absorbed into the systemic circulation and is not delivered to its target tissue, skin.2) To conquer this problem, percutaneous delivery of AA has been challenged. The advantage of percutaneous delivery of AA is (1) to obtain high concentration of AA in the skin and (2) to escape the hepatic first-pass effect before reaching to the systemic circulation. However, when AA is percutaneously administered, the penetration of AA to the dermal tissue is difficult because of the high barrier function of the skin. To increase the permeability of AA, derivatives such asascorbic acid 2-sulfate 8) and disodium isostearyl 2-o-L-ascorbyl phosphate, 9,10) has been developed. Also Gopinath et al. designed ascorbyl palmitate vesicles (Aspasomes) for the transdermal delivery of ascorbic acid.11) Furthermore, recent advances in pharmaceutical technology have promoted the research on the permeability enhancement of AA using physical absorption enhancing method like iontophoresis 12) and microemulsion technologies.11,13) Iontophoresis uses an electric field to drive ionized molecules across the skin by electrophoresis and non-ionized molecules by electro osmosis. 14)Despite concerns about skin irritation, iontophoresis may be useful to deliver some peptides and small proteins.15) On the other hand, microneedles are also one of the physical methods for the percutaneous absorption of drugs. With microneedles, small microconduits are formed on the skin. Recent advance in microfabrication technology has made it possible to prepare microneedles that have a possibility of novel transdermal drug delivery system (TDDS). Since the first publication by Henry et al.,16) microfabrication techniques for the production of silicon, metal, glass and polymer microneedle arrays with micrometer dimensions have been developed. 17-20) The microneedles are either solid or hollow and posses a geometrical shape. Microneedle TDDS is roughly defined by a micron size needle preparation for percutaneous administration. Microneedle TDDSs are classified as follows; (1) extremely small needle through which drug solution can be injected into the skin, (2) metallic and/or silastic microneedles on which surface drug is coated, and (3) metallic and/or silastic microneedles by which microconduits are made on the skin and drug solution is applied after removing the microneedles. H...

Fractional Carbon Dioxide Laser Treatment to Enhance Skin Permeation of Ascorbic Acid 2-Glucoside with Minimal Skin Disruption

“…Much more experimentation needs to be done to determine the clinical situations in which fractional laser treatment with ascorbic acid may be useful, but it seems clear that this method of delivery will give better ascorbic acid delivery to epidermal and dermal skin layers than topical or oral treatment. Little ascorbic acid penetrates below the stratum corneum after topical treatment, and little orally administered ascorbic acid reaches these skin layers, because the capacity of the gastrointestinal active transport system used for absorption limits oral absorption, and the ascorbic acid that is absorbed is quickly undergoes enzymatic and nonenzymatic oxidation and is thus eliminated …”

Microneedles for drug and vaccine delivery

“…Images reproduced with permission from references (a) [113], (b) [112], (c) [127], (d) [126], (e) [140], (f) [50], (g) [119] and (h) [130]. …”

Vitamin C in dermatology

“…C is being explored for the purpose. [5810–13] Extensive research is underway to investigate microspheres, nanoparticles and multilayered microemulsions for graded topical delivery. Trials have been performed with Vit.…”