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.
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