Design and Development of Microformulations for Rapid Release of Small Molecules and Oligonucleotides

  • Eur J Pharm Sci. 2023 May 21;106472. doi: 10.1016/j.ejps.2023.106472.
T Brown  1 ,  M Stanton  1 ,  F Cros  2 ,  S Cho  2 ,  A Kiselyov  3
Affiliations
  • 1. Mosaic Biosciences, 2830 Wilderness Pl, Boulder, CO, 80301, USA.
  • 2. Bionaut Labs, LLC, 3760 Overland Avenue, Los Angeles, CA, 90034, USA.
  • 3. Bionaut Labs, LLC, 3760 Overland Avenue, Los Angeles, CA, 90034, USA. Electronic address: [email protected].
PMID: 37220816 DOI: 10.1016/j.ejps.2023.106472
Abstract

A systemic delivery of therapeutics frequently results in sub-optimal exposure of the targeted locus and undesired side effects. To address these challenges, a platform for local delivery of diverse therapeutics by remotely controlled magnetic micro-robots was introduced. The approach involves micro-formulation of active molecules using hydrogels that exhibit wide range of loading capabilities and predictable release kinetics. This work introduces two specific hydrogels based on thiol-maleimide and PEG-PLA-diacrylate chemistries that afford high, reliable and reproducible loading and release of several model molecules including doxorubicin, 25-mer poly-dT oligonucleotide and a 5.4 kBp GFP DNA plasmid. The described formulations are suitable for micro-dosing using both conventional or remote delivery devices.

Keywords
DNA plasmid; Hydrogel; PEG-PLA-Diacrylate; doxorubicin; micro-formulation; oligonucleotide; thiol-maleimide.
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