Sustained Transdermal Delivery of Tacrolimus Using γ-PGA/PLGA Double-layered Microneedles for Treatment of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is induced by T helper type 2–polarized immune responses and has the characteristics of itch swelling eczema and elevated serum IgE levels This study presents a double-layered [poly(lactic-co-glycolic acid) PLGA]/poly-γ-glutamic acid (γ-PGA) microneedle (MN) and investigate its efficacy for alleviating AD symptoms An immunosuppressant drug tacrolimus (TAC) was encapsulated in the PLGA tip and then combined with an immunomodulatory active compound γ-PGA layer with wound healing and moisturizing effect When inserted into the skin the γ-PGA layer can be quickly dissolved by skin interstitial fluid within 3 min and into the dermis to activate the dendritic cells; the TAC-loaded PLGA tip can be embedded in the skin at a depth of for sustained release of TAC to reduce skin inflammation The TAC loading amount in the PLGA tip was which provided an extended release for up to 4 weeks The MN-created microchannels quickly resealed within two days; however the skin punctured by the MNs without γ-PGA required five days to recover its barrier function After applying the MNs to the Nc/Nga mice with AD-like symptoms the serum levels of IgE IgG1 and IgG2a were also reduced in the MN group indicating that the MNs suppress not only the Th2-type (IgG1 and IgE) but also the Th1-driven antibodies (IgG2a) Additionally the MN treatment can significantly inhibit inflammation-induced epidermal thickening and mast cell infiltrations These results show that the double-layered MN not only has the wound healing activity but also provides sustained release of TAC for long-term management of skin inflammatory Compared to daily topical administration once-a-month MN treatment greatly reduces dosing frequency and has the potential as an attractive alternative in the treatment of AD

Date of Award	2020
Original language	English
Supervisor	Mei-Chin Chen (Supervisor)