Poly(α-hydroxyalkanoic acid): Polymerization methodology, materials, and applications

Synthetic polyester have received tremendous research interest in the past decades. Owing to its wide applications in degradable structure polymers and biomedical fields, there is an increasing need of smart materials that satisfy complex application requirements. The goal of my Ph.D. thesis is to expend the chemistry and materials of poly(α-hydroxyalkanoic acids) (PAHAs). In first part of this dissertation (chapter 2), we developed a metal catalyst based method for preparation of well-defined, side-chain and terminal modified poly(α-hydroxyalkanoic acids) from α-hydroxy acid O-carboxyanhydrides (OCA) monomers. Bon careful screening of ligand and initiator, (BDI)Zn-1 ((BDI-IE)Zn(OCH(CH3)COOCH3), (BDI-IE) = 2-((2,6-diethylphenyl)amino)-4-((2,6-diisopropylphenyl)imino)-2-pentene)) were developed for the controlled ROP of OCAs with various side chains. This catalyst overcame the epimerization problem of conventional organocatalyst, produce highly isotactic PAHAs from chiral OCA monomers, enabled controlled copolymerization of OCAs and lactide, and facilitated the synthesis of block copolymers potentially useful for various biomedical applications. Preliminary mechanistic studies suggest that the monomer/dimer equilibrium of the zinc catalyst influence the ROP of OCAs, with the monomeric (BDI)Zn-1 possessing superior catalytic activity for the initiation of ROP in comparison to the dimeric (BDI)Zn complex. In my second part of work, I focused on developing side-chain modified PAHAs for drug delivery (chapter 3) and gene delivery (chapter 4) applications. In chapter 3, side chain introduced boronic acid was able to successfully tackle encapsulation challenge and formulated doxorubicin encapsulated micelles with high drug loading, quantitative loading efficiency, well-tuned drug release and potent antitumor efficacy. In chapter 4, PAHAs with side chain modified tertiary amine groups was utilized as efficient gene delivery vehicle and high transfection efficiency was achieved. Finally, in chapter 5, we developed a caged metabolic precursor responsive to DT-diaphorase in mammalian cells. The decaging process was finely tuned and trigger responsive cell surface labeling was achieved.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Materials Science & Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2018

Author dc:creator

• Wang, Ruibo

Contributors dc:contributor

• Cheng, Jianjun
• Zimmerman, Steven C.
• Leal, Cecilia
• Evans, Christopher

• polyester
• O-carboxyanhydride
• drug delivery

Statement dc:rights

• Copyright 2018 Ruibo Wang

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/101744

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/101744