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    The effect of PEGylation components on drug release behavior of targeted reduced graphene oxide based drug delivery system
    (2024) Başavcı, Ezgi; Demirel, Erhan; Elhassan, Mohamad; Yüksel Durmaz, Yasemin
    Reduced graphene oxide (rGO) is a restored, defect-free version of graphene oxide (GO) with regained graphene-like properties but encounters challenges in biomedical applications due to its low solubility. Especially for drug release applications, rGO's stronger ?-? interaction of rGO compared to GO leads to low release, often demanding novel approaches for enhancement. The recently developed PEGylation method utilizes a copolymer with tunable PEG chain length and density for the PEGylation of GO simultaneously reduced to rGO, resulting in water-dispersible and biocompatible rGO-based nanoplatforms. This copolymer integrates functional monomers and enhances treatment options. Herein, we investigated how these PEGylation components and their incorporation order impact rGO's drug release behavior. A series of copolymers, (P(PEGMA-co-AzPMA-co-MMA-co-PMA), with different PEG brushes and azide groups, were synthesized via atom transfer radical polymerization. We explored the impact of ionic azide groups on drug release by comparing the azide-containing and azide-capped copolymers. Moreover, copolymers containing 500 or 2000 Da PEG brushes were compared to assess their role as a coating layer or diffusion barrier on drug release. Doxorubicin, a hydrophobic anticancer agent, was loaded onto the rGO surface before or after peptide-based targeting agent (EPPT1) conjugation. The results showed that the drug release behavior of 500 or 2000 Da PEG brushes containing rGO surfaces are different due to the density of PEG coating which makes the effect of azide groups not always visible. Incorporating the targeting peptide before drug loading was found to be optimal. The pH-dependent release profiles revealed 49 % and 44 % release from the rGO surface for the shorter and longer PEG brushes, respectively. Tuning the PEGylation components may further influence the release behavior.