# Long‐Lasting Cross‐Linked PLGA‐Inspired Nanoparticles from One‐Pot Nanopolymerization of Precisely Sequenced Short Oligolactoglycolic Acid Dimethacrylates

## TL;DR

A new method creates stable, long-lasting nanoparticles for drug delivery by precisely sequencing short monomers and encapsulating drugs during formation.

## Contribution

A novel one-pot nanopolymerization technique for creating cross-linked, sequence-controlled PLGA-inspired nanoparticles with enhanced stability and drug encapsulation.

## Key findings

- NPs made with sequence-controlled monomers show minimal pH change and heightened stability over five weeks.
- The method allows for simultaneous nanoparticle formation and efficient encapsulation of drugs like dexamethasone.
- The nanoparticles exhibit low cytotoxicity and uniform cellular uptake in vitro.

## Abstract

A novel PLGA‐inspired NP polymerization technique is presented, which allows the formation of NPs via the cross‐linking of precisely sequenced short oligolactoglycolic acid dimethacrylates (OLGADMAs). Following the synthesis of a range of OLGADMAs, a library of NPs via this rapid and surfactant‐free nanopolymerization method is successfully generated, which permits the simultaneous NP formation and encapsulation of drugs such as dexamethasone. The results indicate that NPs produced through this nanopolymerization technique with precisely controlled sequences exhibit heightened stability compared to conventionally sequenced and non‐sequence controlled PLGA, as evidenced by minimal pH changes over five weeks. This improved stability is attributed to simultaneous crosslinking and co‐polymerization of the OLGADMAs. Moreover, the long‐acting NPs demonstrate minimal cytotoxicity and uniform cellular uptake in vitro. It is concluded that the ability to precisely regulate the sequence of short PLGA‐inspired monomers and employ a unique in situ nanopolymerizing reaction results in exceptionally stable NPs for sustained drug delivery and opens exciting possibilities for the development of a range of long‐lasting drug delivery systems with programmable structure and function.

PLGA‐inspired monomers form highly stable polymeric nanoparticles via a rapid process that allows for simultaneous radical polymerization and nanoparticle formation. Small‐molecule drugs such as dexamethasone undergo a facile in situ encapsulation which occurs with above‐average drug encapsulation efficiencies. The novel synthetic approach yields crosslinked polymeric nanoparticles with desirable drug delivery properties and bears the potential for enabling novel classes of precision nanoparticles.