Novel Molecular Weight Gradient Hyaluronate Dissolving Microneedles for Sustained Intrales-ional Delivery and Photodynamic Activation of Hematoporphyrin in Port-Wine Stain Therapy
PART1
Abstract 摘要
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The re-lease performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the ffrst time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers.
葡萄酒色斑(PWS)是一種進(jìn)行性先天性血管畸形,其特征為真皮毛細(xì)血管擴張,表現(xiàn)出隨年齡增長的病變范圍擴大和顏色加深,從而導(dǎo)致顯著的心理社會共病。雖然全身血卟啉(HP)給藥仍然是光動力療法(PDT)的臨床范例,但其治療效用受到非靶向生物分布的嚴(yán)重限制。藥代動力學(xué)分析顯示,藥物在皮膚的滯留時間延長且病灶部位的藥物積聚不足,致使 42%的患者易出現(xiàn)光毒性反應(yīng)。為解決這些局限性,本研究創(chuàng)新性地提出了一種基于可溶性微針的局部靶向給藥方法,以應(yīng)對上述提到的難題。通過合理設(shè)計分子量(MW)的 HA 梯度系統(tǒng),成功制備出了具有增強生物力學(xué)強度(0.49N/針)和卓越的血卟啉負(fù)載能力的三元納米復(fù)合微針。這些微針共同實現(xiàn)了對血卟啉透皮給藥,并且在 30 分鐘內(nèi)即可完全溶解。血卟啉溶解微針(HP-DMNs)的再釋放性能、皮膚滲透性和儲存穩(wěn)定性都已在體外得到驗實。本研究首次將可溶性微針技術(shù)應(yīng)用于帕金森氏癥的治療中,以實現(xiàn)多巴胺能神經(jīng)遞質(zhì)(HP)的輸送。它通過精確的地方管理避免了系統(tǒng)性暴露的風(fēng)險。它利用微針的快速溶解特性,在皮膚病變中實現(xiàn)藥物的高濃度和快速釋放。這項研究為 PWS 的持續(xù)病灶內(nèi)釋放及快速藥物輸送治療提供了一種新策略,并為新型羥基磷灰石(HP)及其相關(guān)光敏劑的配方開發(fā)提供了新的思路。
PART2
Keywords 關(guān)鍵字
hematoporphyrin; molecular weight gradient design; dissolving microneedles; novel drug delivery; photodynamic therapy
血卟啉;分子量梯度設(shè)計;溶解微針;新型藥物遞送;光動力療法
PART3
Content 內(nèi)容
PART4
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