學生姓名:
孫歆語
指導教授:
黃意真
學期:
110下
摘 要:
Hypertrophic scar (HS) is an unfavorable skin disorder characterized by excessive collagen deposition. Although intralesional injection of bleomycin, triamcinolone acetonide (TA) and 5-fluorouracil (5-Fu) are commonly employed treatments for HS, which, however, always bring pains and require long-term treatment. To overcome these limitations, new methods for enabling painlessness, self-administration, and the fast onset of action are urgently needed. Dissolving microneedles (DMNs) is a minimally invasive transdermal drug delivery system and has been developed to overcome the stratum corneum barrier of skin, which allow the penetration of drugs to epidermis and enhance the transdermal delivery of drugs. Herein, a bleomycin-loaded dissolving microneedles (BMN) made by hyaluronic acid (HA) and a bilayer dissolving microneedle containing TA and 5-Fu (TA-5-Fu-BMN) with biphasic release profile were designed for HS therapy. BMN was found with sufficiently mechanical strength to pierce porcine skin ex vivo with an insertion depth of over 300 μm. Moreover, BMN dissolved rapidly and released 52% of loaded bleomycin within 10 min, and the BMN treated skin could recover to its original status within 3 hr, demonstrating good biocompatibility. Through the in vitro permeation and in vivo HS retention tests, proved that the well-designed biphasic release of TA-5-Fu-BMN could prolong the coexistence of TA and 5-Fu in the scar tissue. Both BMN and TA-5-Fu-BMN were found to inhibit the proliferation of human hypertrophic scar fibroblasts (hHSFs) and the secretion of transforming growth factor-β1 (TGF-β1). In conclusion, the proposed BMN and TA 5-Fu-BMN offer an excellent alternative strategy for clinical treatment of HS in a sustained and minimally invasive manner.
專題討論_20220302_孫歆語_摘要.pdf