Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Biomed Eng. 2020 Nov;4(11):1053-1062. doi: 10.1038/s41551-020-00606-8. Epub 2020 Sep 7.
Eye-drop formulations should hold as high a concentration of soluble drug in contact with ocular epithelium for as long as possible. However, eye tears and frequent blinking limit drug retention on the ocular surface, and gelling drops typically form clumps that blur vision. Here, we describe a gelling hypotonic solution containing a low concentration of a thermosensitive triblock copolymer for extended ocular drug delivery. On topical application, the hypotonic formulation forms a highly uniform and clear thin layer that conforms to the ocular surface and resists clearance from blinking, increasing the intraocular absorption of hydrophilic and hydrophobic drugs and extending the drug-ocular-epithelium contact time with respect to conventional thermosensitive gelling formulations and commercial eye drops. We also show that the conformal gel layer allows for therapeutically relevant drug delivery to the posterior segment of the eyeball in pigs. Our findings highlight the importance of formulations that conform to the ocular surface before viscosity enhancement for increased and prolonged ocular surface contact and drug absorption.
滴眼液制剂应在尽可能长的时间内保持与眼上皮接触的高浓度可溶性药物。然而,眼液和频繁的眨眼会限制药物在眼表面的滞留,而凝胶滴通常会形成团块,导致视力模糊。在这里,我们描述了一种包含低浓度温敏三嵌段共聚物的低渗凝胶溶液,用于延长眼部药物输送。局部应用时,低渗配方形成高度均匀且清晰的薄层,与眼表面一致,并能抵抗眨眼清除,增加亲水性和疏水性药物的眼内吸收,并延长药物与眼上皮的接触时间,与传统的温敏凝胶制剂和商业眼药水相比。我们还表明,这种适应性凝胶层允许将治疗相关药物递送到猪眼球的后段。我们的发现强调了在增加和延长眼表面接触和药物吸收之前,制剂应适应眼表面的重要性。
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