Development of Degradable Diblock Copolymer, Polyphosphoester-Block-Poly(L-Lactide), and Its Conversion into Well-Defined Shell Crosslinked Nanoparticles as Delivery Carriers for Antimicrobial Agents
The combination of state-of-the-art polymerization chemistries, post-polymerization chemical modifications, supramolecular assembly processes and further transformations is allowing for the design of highly well-defined polymer nanoparticles that are demonstrating unique performance toward the effective treatment of infectious diseases. A potentially fully degradable, biocompatible diblock copolymer, polyphosphoester-block-poly(L-lactide) (PPE-b-PLLA), was prepared by one-pot sequential ring-opening polymerizations (ROPs) of two cyclic monomers: alkyne-functionalized phospholane and L-lactide. Photo-induced thiol-yne “click”-type reactions with small molecule thiols bearing carboxylic acid then afforded amphiphilic diblock copolymers with carboxylate side-chain functionalities along the PPE segment of the diblock copolymer backbone. Subsequently, well-defined (1) spherical micelles with negative surface charges were prepared by direct dissolution of the anionic diblock copolymers (aPPE-b-PLLA) in aqueous solution, and (2) shell crosslinked knedel-like (SCK) nanoparticles were prepared by crosslinking of hydrophilic shell of the micelles, as confirmed by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential. The Ag-loading capacities of the anionic micelles and SCKs from aPPE-b-PLLA were determined with three different types of Ag-containing molecules, silver acetate (AgOAc) and silver carbene complexes (SCC22 and SCC10). Similarly, Ag-release kinetics of the Ag-loaded nanoparticles, using dialysis cassettes in nanopure water, was studied. We are currently working on the study of (1) degradation capability of micelles and SCKs of PPE-b-PLLA system under hydrolytic or enzymatic degradation, (2) conjugation with target-specific proteins such as FimHA to evaluate their ability to perform as target delivery carriers, and (3) determination of their in vitro and in vivo efficacies against bacteria.
Abstracts of Papers of the American Chemical Society
Lim, Young H.; Heo, Gyu Seong; Kristin, Tiemann; Shah, Perth N.; Smolen, Justin A.; Cannon, Carolyn L.; Hunstad, David A.; Youngs, Wiley J.; and Wooley, Karen L., "Development of Degradable Diblock Copolymer, Polyphosphoester-Block-Poly(L-Lactide), and Its Conversion into Well-Defined Shell Crosslinked Nanoparticles as Delivery Carriers for Antimicrobial Agents" (2014). Chemistry Faculty Research. 24.