Abstract
The release rates of cortisone hexadecanoate from liposomes were determined in the presence of a rat skeletal muscle homogenate. The presence of such biological material had very little effect on the stability of the cortisone hexadecanoate-DPPC liposome complex, which indicates that an intramuscular injection of liposomes is unlikely to be adversely influenced by enzymes encountered at the injection site. Stability to biodegradation of DPPC liposomes in rabbit blood was enhanced by the incorporation of cholesterol and to a lesser extent cortisone hexadecanoate. All stability assessments in blood were in respect of the leakage rates of an aqueous entrapped marker, namely [ 14C]polyethyleneglycol 4000. Prodrug stability was assessed by determining the hydrolysis rate of the cortisone-21-aliphatic esters in 50% rabbit plasma. The rate of hydrolysis was inversely related to acyl chain length.
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