Lyra Therapeutics, Inc., Watertown, Massachusetts.
Am J Rhinol Allergy. 2022 Mar;36(2):198-206. doi: 10.1177/19458924211039197. Epub 2021 Aug 31.
Intranasal corticosteroid sprays (INCSs) used to treat chronic rhinosinusitis are suboptimal due to limited penetration into the middle meatus, rapid clearance, and poor patient compliance. A bioresorbable drug matrix, developed with the XTreo drug delivery platform, may overcome the limitations of INCS by providing continuous dosing over several months.
To evaluate the in vitro drug release and in vivo pharmacokinetics of novel mometasone furoate (MF) matrices in a rabbit dorsal maxillary osteotomy model.
XTreo matrices were formulated to consistently elute MF for up to 6 months. Matrices were surgically placed bilaterally into the maxillary sinuses of New Zealand White (NZW) rabbits. Tissue and plasma MF concentrations were measured to assess the in vivo drug delivery. The in vivo and in vitro drug release kinetics of the matrices were quantified and compared to those of rabbits receiving daily Nasonex MF nasal sprays.
XTreo matrices self-expanded upon deployment to conform to the irregular geometry of the maxillary sinus cavities in the NZW rabbits. Sustained release of MF was demonstrated in vitro and in vivo for 2 MF matrices of distinct release durations and an in vitro-in vivo correlation was established. Therapeutic levels of MF in local tissues were measured throughout the intended dosing durations. In contrast to the variable peaks and troughs of daily nasal sprays, sustained dosing a single administration of MF matrices was confirmed by quantifiable plasma MF concentrations over the intended dosing duration.
The XTreo MF matrices provided targeted and efficient dosing to local sinus tissues that was superior to INCS. Sustained drug release was confirmed both in vitro and in vivo. The novel XTreo technology may provide precisely tuned, long-lasting drug delivery to sinus tissues with a single treatment.
用于治疗慢性鼻-鼻窦炎的鼻内皮质类固醇喷雾剂（INCS）由于向中鼻甲的穿透力有限、清除速度快和患者顺应性差而效果不佳。一种生物可吸收的药物基质，使用 XTreo 药物输送平台开发，可通过数月内持续给药来克服 INCS 的局限性。
在兔上颌骨切开模型中评估新型糠酸莫米松（MF）基质的体外药物释放和体内药代动力学。
Xtreo 基质被设计为可在长达 6 个月的时间内持续释放 MF。将基质通过手术双侧置于新西兰白兔的上颌窦中。测量组织和血浆 MF 浓度以评估体内药物输送。定量和比较了基质的体内和体外药物释放动力学，以及接受每日 Nasonex MF 鼻喷雾剂的兔子的药物释放动力学。
Xtreo 基质在部署后自扩张，以适应新西兰白兔上颌窦腔的不规则几何形状。在体外和体内均证明了两种具有不同释放持续时间的 MF 基质的持续释放，并且建立了体外-体内相关性。在整个预期给药时间内，局部组织中均测量到 MF 的治疗水平。与每日鼻喷雾剂的可变峰值和谷值不同，通过可量化的血浆 MF 浓度证实了 MF 基质的持续给药，单次给药即可实现。
Xtreo MF 基质为局部鼻窦组织提供了靶向和有效的给药，优于 INCS。在体外和体内均证实了持续的药物释放。新型 XTreo 技术可通过单次治疗为鼻窦组织提供精确调谐的长效药物输送。
