Synthesis, characterization, and bio-applications of peptide hybrid materials

• Main Authors: Peng, Sydney, 彭心怡
• Other Authors: Chu, I-Ming
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/06646829981962506963

博士 === 國立清華大學 === 化學工程學系 === 103 === In the recent decades, polymer scientists have begun to look into the remarkable achievements of nature to extract particular knowledge for the design of improved biomaterials. This has led to an increase in hybrid polymers that use biological concepts to control the structures and properties of these hybrids. Combining synthetic materials with peptides, the basic building block of the body, into a single macromolecule offers many possibilities previously unachievable with a single material. Peptides have the tendency to arrange into a variety of secondary structures that may be exploited in copolymer systems for their stabilizing and self-assembling character through hydrogen bonding. This dissertation sets out to study a collection of poly(ethylene oxide)-peptide materials and discusses their synthesis method, chemical and physical characteristics, and potentials as nanoscale carrier and hydrogel for use in drug and cell delivery. This study uses amine-terminated PEO-based polymers to initiate ring-opening polymerization (ROP) of N-carboxyanhydride (NCA) form of different amino acids to provide peptide hybrid materials. These materials exhibit the propensity for secondary structure formation in both solid and solubilized forms to provide stability and formation of distinct microarchitectures. Two different PEO-based polymers were used, including poly(ethylene oxide) – poly(propylene oxide) – poly(ethylene oxide) (PEO-PPO-PEO, Pluronic®) and methoxy poly(ethylene glycol) (mPEG). In the first section, amine-terminated Pluronic was used to synthesize a series of Pluronic-oligo(alanine) and Pluronic-oligo(phenylalanine) copolymers. These copolymers were characterized and evaluated for their ability to carry a model hydrophobic drug, curcumin. The encapsulation efficiency of curcumin increased drastically after the addition of peptides. Furthermore, increased cytotoxicity against HeLa cells and cellular uptake were observed with alanine-contianing nanoparticle formulations. These copolymers were also prepared as thermosensitive hydrogels and exhibited decreased gelation concentration, extended in vitro and in vivo residence time, increased cell compatibility, and change in microarchitecture when compared to native Pluronic. Taken together, results suggest that this material may be suitable for various bio-applications In the second half of the study, amine-terminated mPEG was used to synthesize a series of neutral, positively charged, and negatively charged copolymers using alanine-NCA, lysine-NCA, and aspartic acid-NCA respectively. The microarchitecture of mPEG-poly(alanine) differed significantly from those of other synthetic thermosensitive hydrogels in its strand-like appearance. Chondrocytes cultured within these hydrogels formed homogenous cell clusters with prolonged incubation. Biochemical analysis and real time polymerase chain reaction (real time RT-PCR) were used to evaluate the relationship between hydrogel characteristics and chondrogenic potential of encapsulated chondrocytes. In the final section, oligo(lysine) and oligo(aspartic acid) were added to the peptide end of mPEG-poly(alanine) to increase solubility, helical stability, and confer pH sensitivity. In summary, these studies demonstrated that peptide hybrid materials are a feasible option for various bio-applications ranging from drug delivery to tissue engineering in both nanoparticle and hydrogel forms. These structures showed excellent stability and potential degradability in vivo as well as biomimetic character. Further in vivo evaluations are underway to examine the ability of hydrogels to support extended drug release and tissue generation. These materials clearly hold promise as an interesting class of biomaterial with a wide range of application.