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自上而下法制备多层肠溶给药系统用于口服递送多肽。

Bottom-Up Fabrication of Multilayer Enteric Devices for the Oral Delivery of Peptides.

机构信息

UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.

Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA.

出版信息

Pharm Res. 2019 Apr 19;36(6):89. doi: 10.1007/s11095-019-2618-3.

Abstract

PURPOSE

To develop a planar, asymmetric, micro-scale oral drug delivery vehicle by i) fabricating microdevice bodies with enteric materials, ii) efficiently and stably loading sensitive drug molecules, and iii) capping microdevices for controlled drug release.

METHODS

Picoliter-volume inkjet printing was used to fabricate microdevices through additive manufacturing via drop-by-drop deposition of enteric polymer materials. Microdevice bodies with reservoirs are fabricated through deposition of an enteric polymer, Eudragit FS 30 D. A model API, insulin, was loaded into each microdevice and retained its stability during printing and release. Eudragit L 100 and/or S 100 were used to cap microdevices and control the kinetics of insulin release in simulated intestinal conditions.

RESULTS

Microdevice morphologies and size can be tuned on the fly based on printing parameters to span from the microscale to the mesoscale. Insulin retained its stability throughout device fabrication and during in vitro release in simulated intestinal conditions. Insulin release kinetics, from burst release to no release, can be tailored by controlling the blend of the Eudragit capping material.

CONCLUSION

This approach represents a uniquely scalable and flexible strategy for microdevice fabrication that overcomes limitations in loading sensitive biologics and in the tuneability of device geometries that are inherent to traditional microfabrication strategies.

摘要

目的

通过以下方法,开发一种平面、非对称、微尺度的口服药物输送装置:i)用肠溶材料制造微器件主体;ii)高效稳定地载入敏感药物分子;iii)密封微器件以控制药物释放。

方法

采用微升体积喷墨打印技术,通过逐滴沉积肠溶聚合物材料进行添加剂制造,制造微器件。通过沉积肠溶聚合物 Eudragit FS 30 D 制造具有储液器的微器件体。将模型 API 胰岛素载入每个微器件中,并在打印和释放过程中保持其稳定性。使用 Eudragit L 100 和/或 S 100 对微器件进行密封,以控制胰岛素在模拟肠条件下的释放动力学。

结果

根据打印参数,可以即时调整微器件的形态和尺寸,从微观尺度到中观尺度。胰岛素在整个器件制造过程中以及在模拟肠条件下的体外释放过程中均保持稳定。通过控制 Eudragit 密封材料的混合物,可以调整胰岛素的释放动力学,从突释释放到无释放。

结论

该方法代表了一种独特的可扩展和灵活的微器件制造策略,克服了传统微制造策略中固有的载入敏感生物制剂和调整器件几何形状的局限性。

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