The hydrophobicity of many drugs poses a major problem for delivery to target tissues. One current technique for hydrophobic drug delivery utilizes Human Serum Albumin (HSA). Hydrophobic binding pockets on HSA protect the molecule from degradation due to redox reactions, hydrolysis and immunogenic response. Bovine Serum Albumin (BSA) provides a cheaper, more readily available alternative to HSA. Structural similarities between binding pockets of both species suggest similar binding capabilities. Conjugation of multiple BSA molecules onto an 8-arm polyethylene glycol backbone (PEG8-BSAx) addresses concerns about the effect on osmotic pressure, competition for binding sites, and immunogenicity. Utilizing SPAAC, multiple dibenzocyclooctyl-functionalized de-fatted BSA were attached to an azido-functionalized PEG8. CD demonstrated no loss of secondary structure after PEGylation. Four high molecular weight PEG8-BSAx species were separated from the reaction mixture via SDS-PAGE and reversed phase HPLC. Ligand-binding capabilities and dissociation constants were determined using the fluorescent probe ANS. Multiple BSA molecules were successfully conjugated onto a PEG8 framework while maintaining ligand-binding capabilities. These results suggest that PEG8-BSAx is a viable delivery system for water-insoluble pharmaceuticals.

Conjugation of BSA onto PEG8 via strain-promoted azide-alkyne cycloaddition (SPAAC) as a drug delivery system

251st National Meeting (2016)

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