Covalent binding of hydrocortisone and dexamethasone to hydrophylic biocompatible macromolecular carriers through hydrolizable carbonate linkage was investigated according to two complementary strategies. (a) Radical copolymerization of hydrocortisone‐21C‐vinylcarbonate with N‐vinylpyrrolidone (NVP,60°C), or N‐[tris(hydroxymethyl)methyl]acrylamide (THMMA, 50°C) in dimethylacetamide solution: In spite of a nearly zero reactivity ratio for the steroid monomer which behaves as a degradative transfer agent—CT ∼ 5.7 × 10−2 and 6.8 × 10−3 for NVP and THMMA, respectively–this process may afford fairly high molecular weight polymers (M̄w ≃ 104–105) with high enough hydrocortisone content (0.03–0.10 mole.fraction). (b) Condensation of the hydrocortisone or dexamethasone‐21C‐chloroformates onto poly(oxyethylene glycol) (M̄n = 6220) or hydroxypropylcellulose (HPC, M̄w = 1.35 × 105) in tetrahydrofuran solution (30°C): This straightforward process is of low efficiency (yields >50%), and only HPC derivatives show good chemical homogeneity.

SynopsisThe release of hydrocortisone and dexamethasone due to hydrolysis of the carbonate linkage from the polymeric supports of polfloxyethyleneglycol), hydroxypropyl cellulose, and N-vinylpyrrolidone/hydrocortisone-z1CHz-vinylcarbonate copolymer was observed in a living system, by induction of aGPDH activity in rat C6 glial cells, and in uitro by a kinetic study of release in aqueous sodium phosphate buffer medium. The glucocorticoid reiease is pH and temperature dependent and highly sensitive to steric hindrance. In uiw, testing on antiinflammatory activity in rats with poly foxyethyleneglycol) and hydroxypropyl cellulhse bound dexamethasone was performed. However, it produced negative results probably due to difficulty in splitting the carbonate linkage in the inflammatory region of acidic pH values.