Synthesis of PHB-based carrier for drug delivery systems with pH-controlled release

• Selective transformation of PHB crotonate into PHB glyoxylate via ozonolysis.
• Model drug delivery system – conjugate of PHB glyoxylate with primary amine.
• pH-controlled release of amine from the model conjugate.

Synthetic route to prepare model PHB-amine conjugate containing hydrolysable imine bond is reported. Short-chain PHB crotonate is converted into PHB glyoxylate via clean and efficient ozonolysis followed by reductive decomposition of peroxidic products with dimethylsulfide. Aldehyde-functionalized PHB is obtained quantitatively without polymer backbone degradation while PHB-amine conjugate is synthesized with very high yield. Release properties of such-prepared conjugate is confirmed in hydrolysis experiment revealing pH-dependent kinetics of amine release. Simplicity of the protocol in conjunction with unique properties of PHB carrier are believed to be powerful tool for development of novel drug conjugates.

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