Chemical tailoring of micelle-forming poly(ethylen oxide)-block-poly(ester) copolymers for drug delivery

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Design and development of novel synthetic biomaterials that adequately solubilize therapeutic agents, release them in an appropriate rate and location, and at the same time, are safe for application in humans is the main purpose of this research. Such compounds are expected to mimic the function of biological transport systems: be recognized as self within the body, carry adequate quantities of the drug to its site of action, release their therapeutic cargo in the vicinity of their cellular and molecular targets and degrade to biocompatible components afterwards. In this context, synthetic biomaterials may be advantageous to their biological counterparts due to the ease of structural modifications, stability and safety of administration. In the first part of this project, we have developed novel self associating block copolymers consisting of poly(ethylene oxide)-poly(ester)s bearing pendent carboxyl or aromatic groups on the poly(ester) block. The developed block copolymers are bio-compatible due to the poly(ethylene oxide), biodegradable due to poly(ester), can self associate to nanoscopic micellar structures due to the amphiphilic nature of the polymer, and allow chemical conjugation and/or physical interaction with hydrophobic or hydrophilic molecules within the micellar core due to the presence of different side groups on the poly(ester). These biomaterials structurally and functionally are close to natural drug carriers in blood, i.e., lipoprotein, but have the advantage of chemical flexibility. In the second part of the project, we will pursue development of artificial viruses for the delivery of nuclearic acid based therapeutics. Development of polymeric nano-carriers that can incorporate DNA and RNA structures by electrostatic or hydrophobic interactions and deliver them to appropriate intracellular targets will be pursued. The proposed structures will be based on biocompatible and biodegradable poly(ethylene oxide)-poly(ester) block copolymers bearing targeting ligands on the poly(ethylene oxide) shell and hydrophobic and cationic groups in the poly(ester) core.