Date of Award

Fall 2007

Project Type


Program or Major

Materials Science

Degree Name

Master of Science


The oral delivery of therapeutic compounds, from small molecules to proteins, is one of the most desirable routes of administration. Its advantages reside in low cost, patient compliance and ease of use. The major challenge associated to such a delivery route is the transport through the gastrointestinal tract (GIT). In the case of complex and fragile molecules such as proteins, this particular step is the source of multiple challenges. Among the approaches developed to protect the therapeutic compound, the use of polymeric carriers is the most promising. We developed biocompatible and biodegradable polymersomes formed by the self assembly of amphiphilic copolymers in water. The copolymers we used are a combination of the following homopolymers: poly(ethylene glycol), poly(lactic acid), poly(caprolactone) and poly(glutamic acid). The PEG-PLA or PLA blocks were prepared by ring opening bulk polymerization (ROP) using an organic catalyst, and an alcohol as initiator. The poly(glutamic acid) was prepared aside by ROP of the benzyl glutamate N-CarboxyAnhydride (NCA), followed by the deprotection of the benzyl group. The final copolymer was obtained by coupling a PEG-PLA (or PLA) to a PGluOH. Another synthesis route was explored. It consists in the preparation of a macro amine, namely PEG-PLA-(NH 2)x, used to ring open the benzyl glutamate NCA. The PEG-PLA-PGluBn is then deprotected. The polymer chains obtained by one of these two synthesis routes self assemble in basic water into well defined vesicles with diameter ranging from 70 to 100 nm. They can be loaded with insulin and orally delivered. The vesicles are progressively degraded along the GIT before transport through intestine wall and insulin is released. A full characterization of the polymers and a study of the morphology of self assemblies constitute the bulk of this work.