Ammonium trifluoroborate-modified poly(ß-aminoesters): A case study for PET-guided in vivo pharmacokinetic studies of a non-viral gene delivery system.
J Control Release
; 358: 739-751, 2023 06.
Article
in En
| MEDLINE
| ID: mdl-37207793
ABSTRACT
Nucleic acid-based therapies have become a game-changing player in our way of conceiving pharmacology. Nevertheless, the inherent lability of the phosphodiester bond of the genetic material with respect to the blood nucleases severely hampers its delivery in naked form, therefore making it necessary to use delivery vectors. Among the potential non-viral vectors, polymeric materials such as the poly(ß-aminoesters) (PBAEs) stand out as promising gene carriers thanks to their ability to condense nucleic acids in the form of nanometric polyplexes. To keep advancing these systems into their translational preclinical phases, it would be highly valuable to gain accurate insights of their in vivo pharmacokinetic profile. We envisaged that positron emission tomography (PET)-guided imaging could provide us with both, an accurate assessment of the biodistribution of PBAE-derived polyplexes, as well shed light on their clearance process. In this sense, taking advantage of the efficient [19F]-to-[18F]fluorine isotopic exchange presented by the ammonium trifluoroborate (AMBF3) group, we have designed and synthesized a new 18F-PET radiotracer based on the chemical modification of a linear poly(ß-aminoester). As proof of concept, the incorporation of the newly developed 18F-PBAE into a model nanoformulation was shown to be fully compatible with the formation of the polyplexes, their biophysical characterization, and all their in vitro and in vivo functional features. With this tool in hand, we were able to readily obtain key clues about the pharmacokinetic behavior of a series of oligopeptide-modified PBAEs (OM-PBAEs). The observations described in this study allow us to continue supporting these polymers as an outstanding non-viral gene delivery vector for future applications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Transfer Techniques
/
Positron-Emission Tomography
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2023
Document type:
Article