Polymer-based Nanoparticle Design And Synthesis For Drug Delivery Applications



Journal Title

Journal ISSN

Volume Title



The many advantages when using drug delivery systems such as delivery of hydrophobic drugs and increased circulation and retention time among others, is constantly driving to the development of new and more practical polymeric nanonetworks. The creation of new materials such as block copolymers and nanosponges present synthetic versatility for various applications including those in the biomedical field. This dissertation focuses on the synthesis of polymeric macrostructures, such as nanosponges and micelles, to serve as drug delivery systems of hydrophobic drugs. We present the further development of second generation nanosponges. The nanosponges are composed of poly(δ-valerolactone-co-2-oxepane-1,5-dione) and poly(itaconaic acid-co-succinic acid) polymer precursors that can intermolecularly crosslink via a difunctional crosslinker to form 3D spherical polymeric architectures. These nanosponges are highly tunable in dimensions when various parameters are modified including molecular weight of the polymer precursor, percentage of reactive unit incorporated, reaction concentrations, crosslinker equivalents, and others. These nanosponges have demonstrated to possess hydrophobic compartments capable of encapsulating drugs such as doxorubicin and imatinib. In addition, we present the synthesis of the first polymeric formaldehyde prodrug that renders the gaseous molecule intact until it reaches the delivery location due to a pH trigger mechanism. This formaldehyde polymeric prodrug can serve as the matrix for the dispersion of the nanoparticles made out of poly(δ-valerolactone-co-2-oxepane-1,5-dione) that can encapsulate doxorubicin. The combination of the formaldehyde polymer prodrug and the doxorubicin-loaded nanosponges is used for dual delivery of doxorubicin and formaldehyde for synergistic effect. Similarly, the synthesis of block copolymers is also presented with the study of metal-organic insertion light initiated radical (MILRad) polymerization developed in our laboratory. Several cationic Pd-complexes were studied for the homopolymerization of acrylamides and an active ester. The copolymerization of vinyl monomers with olefins such as hexene and ethylene allowed for the formation of polar - non-polar block copolymers capable of assembling into micelles. We envision these micelles could serve for encapsulation of hydrophobic drugs along with the modification of the active ester moieties for placement of targeting units that can facilitate the drug delivery applications.



Polymer, Drug delivery systems, Formaldehyde, MILRad


Portions of this document appear in: Ordonez, Estela, Laken L. Kendrick-Williams, and Eva Harth. "Formaldehyde-doxorubicin dual polymeric drug delivery system for higher efficacy and limited cardiotoxicity of anthracyclines." European Polymer Journal 143 (2021): 110210.