Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

Attia, Lucas; Chen, Liang‐Hsun; Doyle, Patrick S.

doi:10.1002/adhm.202301667

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery

Journal Article · Thu Aug 10 00:00:00 EDT 2023 · Advanced Healthcare Materials

DOI:https://doi.org/10.1002/adhm.202301667· OSTI ID:1994893

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Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139 USA
Department of Chemical Engineering Massachusetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139 USA, Campus for Research Excellence and Technological Enterprise Singapore 138602 Singapore

Abstract

Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual‐responsive gelation process that exploits orthogonal thermo‐responsive and ion‐responsive gelations is introduced. This one‐step “dual gelation” synthesizes core–shell (methylcellulose‐alginate) hydrogel particles and encapsulates drug‐laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed‐dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core–shell hydrogel particles.

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Sponsoring Organization:: USDOE

OSTI ID:: 1994893

Alternate ID(s):: OSTI ID: 1995590
OSTI ID: 2575752

Journal Information:: Advanced Healthcare Materials, Journal Name: Advanced Healthcare Materials Journal Issue: 31 Vol. 12; ISSN 2192-2640

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Germany

Language:: English

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