Nanocarriers for Drug Delivery Applications: From Tunable Morphologies to Glycopolymer-coated Vesicles

Amphiphilic block copolymers are well known to undergo self-assembly in aqueous solution into a variety of core/shell structures making them useful for various health applications. These different architectures are largely a result of the hydrophilic volume or weight fraction of the block copolymer. In drug delivery, differences in morphology can largely impact performance and each provides their individual advantages. Polymer vesicles, commonly referred to as polymersomes, have received significant attention due to their resemblance to biological membranes and multifunctional capabilities. This thesis describes the use of novel polyester block copolymers containing a hydrophilic poly(ethylene oxide) block and a hydrophobic poly(hydroxyalkanoate) block bearing alkene functionality. These polyester block copolymers can be functionalized using orthogonal chemistry with a number of molecules in order to tune their hydrophilic weight fraction and obtain a variety of different desirable morphologies. Additionally, this thesis will describe the synthesis of glycopolymer-coated vesicles using RAFT polymerization for their potential application in targeted drug delivery

Post-polymerization functionalization of poly (ethylene oxide)–poly (β-6-heptenolactone) diblock copolymers to tune properties and self-assembly

Polyester-based amphiphilic block copolymers and their nanoassemblies are of significant interest for a wide range of applications due to the degradability of the polyester block. However, the commonly used polyesters lack functional groups on their backbones, limiting the possibilities to chemically modify these polymers. Described here are new poly(ethylene oxide) (PEO)–poly(β-6-heptenolactone) (PHEL) block copolymers having pendant alkenes at each repeat unit on the PHEL block. First, the self-assembly of these block copolymers in aqueous solution was studied and it was found that they formed solid nanoparticles and vesicles depending on the relative block lengths. Next the alkene moieties of the block copolymer were modified with either hydrophilic or hydrophobic pendant groups using thiol–ene reactions, allowing the hydrophilic mass fractions and consequently the self-assembled morphologies to be tuned, accessing both smaller nanoparticles and cylindrical assemblies. It was also demonstrated that the anti-cancer drug paclitaxel or a fluorescent rhodamine dye could be easily conjugated to the block copolymers and the self-assembly of these conjugates was explored. Overall, the results of this study demonstrate that PEO-PHEL block copolymers can serve as versatile backbones for the preparation of functional, polyester-based materials

Post-polymerization functionalization of poly(ethylene oxide)–poly(β-6-heptenolactone) diblock copolymers to tune properties and self-assembly

Copolymers were synthesized and functionalized with a variety of moieties to tune self-assembly and install drugs or fluorescent dyes. , Polyester-based amphiphilic block copolymers and their nanoassemblies are of significant interest for a wide range of applications due to the degradability of the polyester block. However, the commonly used polyesters lack functional groups on their backbones, limiting the possibilities to chemically modify these polymers. Described here are new poly(ethylene oxide) (PEO)–poly(β-6-heptenolactone) (PHEL) block copolymers having pendant alkenes at each repeat unit on the PHEL block. First, the self-assembly of these block copolymers in aqueous solution was studied and it was found that they formed solid nanoparticles and vesicles depending on the relative block lengths. Next the alkene moieties of the block copolymer were modified with either hydrophilic or hydrophobic pendant groups using thiol–ene reactions, allowing the hydrophilic mass fractions and consequently the self-assembled morphologies to be tuned, accessing both smaller nanoparticles and cylindrical assemblies. It was also demonstrated that the anti-cancer drug paclitaxel or a fluorescent rhodamine dye could be easily conjugated to the block copolymers and the self-assembly of these conjugates was explored. Overall, the results of this study demonstrate that PEO-PHEL block copolymers can serve as versatile backbones for the preparation of functional, polyester-based materials

On invisible trade relations between Mesopotamian cities during the third millennium BC

The idea that the emergence of writing was necessity due to the increase in both die number of economic transactions and political complexity has been recently emphasized by Matthews, who also underlines that writing acted as a feedback in enabling and encouraging the growth of ever more complex modes of exchange. The intertwinement of trade and writing suggests that clay tablets left by the civilizations from the third millennium B.C. in Mesopotamia, where writing was invented, may be considered as traces of trade links and transactions between cities. We estimate a gravity model based on clay tablets, as if they represented trade flows. The parameters lead us to conclude that Mesopotamia formed a strongly integrated market