Antiinflammatory polymer‐bound steroids for topical applications. I. Synthesis and characterization

Abstract

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.

Functionalized Poly(ethylene glycols) for Preparation of Biologically Relevant Conjugates

“…In a few cases attachment of biologically relevant molecules to PEG was achieved directly by utilizing the reactivity of terminal primary OH groups of the commercially available polymer. Examples for preparation of various conjugates containing ether (30,31), ester (7,(32)(33)(34), or carbonate (35) linkages were described. Ester formation with carboxylic acid containing molecules is a particularly clean reaction, which can be driven to completion under very mild conditions (36).…”