(482a) Therapeutic Proteins and Degradable Polymersomes

Therapeutic proteins are generally potent but short-lived, which has motivated recent work on protein modification by polyethylene glycol (PEG). We are instead investigating the ability of PEG-based block copolymer vesicles ? or polymersomes ? to encapsulate such proteins for controlled release, and in the process studying the interactions between block copolymers and complex, aggregating proteins. We are using recombinant human insulin (MW 6 kDa) as one therapeutic protein for encapsulation and tuned release. Insulin administration is typically effective only on a timescale of minutes, while PEGylation extends insulin activity to several hours. However, such chemical modifications of protein are not always specific and can also alter activity, further motivating encapsulation within vesicles. Whereas lipid vesicles do not allow for tunable release kinetics, the release of insulin from our polymersomes is varied through blend ratios of degradable copolymer (eg. PEG-polylactic acid) and inert PEG copolymer. Polymersomes otherwise provide stability and protection, even at low pH, and also increase the active half-life up to ~20 hrs or more in circulation. However, insulin is literally a complex protein, and the results for encapsulation of this and other proteins will attempt to clarify some of the principles perhaps unique to polymersome-based encapsulation of therapeutic proteins.