Purpose: Prostaglandins have potent and diverse biologic activities, but their clinical application is severely restricted, mainly due to rapid inactivation in vivo. In order to modulate the pharmacokinetics of prostaglandin E(1) (PGE(1)), we prepared biodegradable nanoparticles as a drug carrier.
Methods: Nanoparticles encapsulating PGE(1) were prepared from a blend of poly(lactic acid) homopolymer and poly(ethylene glycol)-poly(lactide) block copolymer by the solvent diffusion method in the presence of iron.
Results: PGE(1) was efficiently and stably embedded in the nanoparticles through interaction with iron, despite being relatively hydrophilic and having unstable chemical properties. Depending on the isomers and molecular weight of poly(lactic acid) selected, PGE(1) was gradually released from the nanoparticles at various rates into diluted serum in vitro. Both stable retention of PGE(1) in the nanoparticles and coating of the nanoparticles with poly(ethylene glycol) led to an extremely extended blood residence time of PGE(1), as well as preferential accumulation in vascular lesions.
Conclusions: These results suggest that the present strategy is useful to advance the clinical application of PGE(1) as a therapeutic agent for vascular disorders.
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