Design and development of microformulations for rapid release of small molecules and oligonucleotides

T Brown; M Stanton; F Cros; S Cho; A Kiselyov

doi:10.1016/j.ejps.2023.106472

Design and development of microformulations for rapid release of small molecules and oligonucleotides

Eur J Pharm Sci. 2023 Sep 1:188:106472. doi: 10.1016/j.ejps.2023.106472. Epub 2023 May 21.

Authors

T Brown¹, M Stanton¹, F Cros², S Cho², A Kiselyov³

Affiliations

¹ Mosaic Biosciences, 2830 Wilderness Pl, Boulder, CO, 80301, USA.
² Bionaut Labs, Inc., 3767 Overland Avenue, Los Angeles, CA 90034, USA.
³ Bionaut Labs, Inc., 3767 Overland Avenue, Los Angeles, CA 90034, USA. Electronic address: alex.kiselyov@bionautlabs.com.

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; Doxorubicin; Hydrogel; Micro-formulation; Oligonucleotide; PEG-PLA-diacrylate; Thiol-maleimide.

MeSH terms

DNA
Doxorubicin
Hydrogels
Oligonucleotides*
Polyethylene Glycols*

Substances

Oligonucleotides
Polyethylene Glycols
Hydrogels
Doxorubicin
DNA