Poly(glycerol adipate) - indomethacin drug conjugates - synthesis and in vitro characterization

- Polymeric prodrugs with different indomethacin contents were synthesized representing a promising new drug delivery system.
- Hydrophobicity, glass transition temperature, complex viscosity increase with higher indomethacin content.
- Tailoring of a polymeric prodrug with desired properties is possible.

The linear biodegradable polyester poly(glycerol adipate) (PGA) was synthesized via enzymatic polycondensation using lipase B from Candida antarctica (CAL-B). Every monomer unit of PGA possesses a pendant hydroxyl group which is responsible for the hydrophilic character and moisture swelling. These OH groups were esterified to different degrees with the anti-inflammatory drug indomethacin in order to create a prodrug with a pH-sensitive linker for modified drug release. The structure of the conjugates was determined via ATR FT-IR spectroscopy, NMR spectroscopy, GPC and UV/VIS spectroscopy. The physical properties of polymers with different drug load were investigated using DSC, contact angle measurements and oscillatory rheology. Drug release was monitored over one month in vitro. A very slow, but continuous release was observed in PBS. Slightly acidic conditions and lipase activity are accelerating the indomethacin release. Therefore, poly(glycerol adipate) − indomethacin conjugates are promising prodrugs for the local sustained release of indomethacin.

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