利用可溶性微針包覆核黃素作為角膜藥物傳遞之工具

Abstract

眼角膜膠原蛋白交聯利用核黃素/紫外線搭配刮除角膜上皮，已被視為有效延緩圓錐角膜惡化及其他角膜疾病的療法。在本篇研究中，利用可溶性微針突破角膜上皮屏障將核黃素導入角膜，微針由生物相容性材料製作而成，並在實驗中測試微針穿刺角膜的能力及穿刺深度等特性，以及評估含藥微針角膜上之藥物穿透釋放能力及應用於膠原蛋白交聯術之效果，根據我們實驗的結果顯示，使用含有50%高分子且包裹0.6%核黃素的微針施行膠原蛋白交聯術，相較於滴核黃素溶液在角膜上，有較好的藥物穿透性，而在機械性質及抗酵素分解的能力上也有增加的效果。綜觀而言，本篇研究揭示了可溶性高分子微針的製作方法以及配方，證明其可成功地將水溶性藥物傳導入角膜基質中，因此，本研究之結果提供一個有發展潛力的工具，用於提高角膜膠原蛋白交聯手術效果以及病患順應性。

Corneal collagen cross-linking with Riboflavin/UVA coupling with corneal epithelium removal has already been recognized as effective therapy for limiting the progression of keratoconus and other corneal disorders. In the study, dissolving microneedles were used to bypass the corneal epithelium barrier enhancing ocular drug delivery of Riboflavin. MNs were fabricated using biocompatible materials, polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) polymers, with conical shape and characterized for their insertion puncture forces and insertion depth. The MNs containing Riboflavin were investigated by in vitro drug permeation and corneal crosslinking effect comparing to topical application of Riboflavin solution. According to our results, 50% (w/w) PVP produced MNs containing 0.6% Riboflavin demonstrated high drug permeation with constant release comparing to topical applied aqueous solutions, an increase of tensile modulus and enzymatic digestion resistance comparing to untreated corneas. Overall, this study reported the fabrication and formulation of minimally invasive rapidly dissolving polymeric MNs which were able to efficiently deliver hydrophilic drug to the corneal stroma. Thus, it becomes potential manner to enhancing ocular delivery for improving efficiency and patient compliance to the corneal collagen crosslinking procedure.