Polymeric micelles have been heavily investigated for their use as delivery vehicles for poorly soluble, potent chemotherapeutics. While these systems have shown clinical promise, poor stability and low drug encapsulation have hindered transfer of many formulations into the clinic. Our lab has designed a biodegradable polymer comprised of a hydrophobic copolymer backbone and a hydrophilic graft, forming a unique co-polymer, poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG)1.  This polymer self-assembles in water to form polymeric micelles with low dispersity.In order to make micelles with improved stability and higher drug loading, we asked how changes to both the hydrophilic corona and the hydrophobic core would affect serum stability and drug encapsulation, respectively. The free carboxylates on the TMCC of the backbone were used to chemically modify the polymer and tune its properties for drug delivery.  The hydrophilic corona was modulated by controlling the number of grafted PEG chains using carbodiimide chemistry. Micelle characterization and stability studies revealed that increasing coronal PEG density prevents particle aggregation under both serum-containing conditions and through the freeze-drying process, eliminating the need for stabilizing excipients. The hydrophobic core was tuned for greater hydrophobic drug encapsulation by modifying the carboxylates on the backbone with hydrophobic groups.  Combined, our polymeric micelles have superior stability and improved drug loading, creating a drug delivery system that overcomes many of the current challenges.1. Lu, J. & Shoichet, M. S. Self-Assembled Polymeric Nanoparticles of Organocatalytic Copolymerizated d, l-Lactide and 2-Methyl 2-Carboxytrimethylene Carbonate. Macromolecules 43,  4943�4953 (2010).

Tuning polymeric micelle stability and drug loading with selective chemical modifications

248th National Meeting (2014)

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