Cameron L Nemeth1, William R Lykins1, Huyen Tran2, Mohamed E H ElSayed3, Tejal A Desai4,5. 1. UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA. 2. Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA. 3. Eli Lilly and Company Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA. mohamed.elsayed@lilly.com. 4. UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA. Tejal.desai@ucsf.edu. 5. Bioengineering & Therapeutic Sciences, UCSF School of Pharmacy, San Francisco, CA, USA. Tejal.desai@ucsf.edu.
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.
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.
Authors: Juliane Fjelrad Christfort; Antonio José Guillot; Ana Melero; Lasse Højlund Eklund Thamdrup; Teresa M Garrigues; Anja Boisen; Kinga Zór; Line Hagner Nielsen Journal: Pharmaceutics Date: 2020-04-14 Impact factor: 6.321