Prolonging the In Vivo Residence Time of Prostaglandin E1 with Biodegradable Nanoparticles

Abstract

These results suggest that the present strategy is useful to advance the clinical application of PGE(1) as a therapeutic agent for vascular disorders.

Development, Optimization, and Characterization of PEGylated Nanoemulsion of Prostaglandin E1 for Long Circulation

“…Tsutomu Ishihara et al (19) developed nanoparticles that efficiently incorporated PGE1 by blending PLA homopolymers and PEG-PLA block copolymers in the presence of iron. This formulation prevented the inactivation of PGE1, exhibited a long-term therapeutic effect due to slow release along with degradation of the polymers, and controlled the biodistribution to target sites.…”

“…A number of new alternative dosage forms of PGE1, such as lipid microspheres (15), inhaled PLGA particles (16)(17)(18) for pulmonary arterial hypertension, and nanoparticles (19)(20)(21)(22), can prevent PGE1 from inactivation in blood and improve the efficacy of PGE1. Among these new dosage forms, PGE1 lipid microspheres (lipo-PGE1) were established by Mizushima (15).…”

Synthesis of Prostaglandin E1 Phosphate Derivatives and Their Encapsulation in Biodegradable Nanoparticles

“…AS-013 was from our laboratory stock. PEG-D,L-PLA (average molecular weight of PEG and PLA are 5,600 and 9,400, respectively) was synthesized and evaluated as described previously (18,30). Porcine liver esterase (PLE) and human placenta alkaline phosphatase (ALP) were purchased from Sigma-Aldrich Co. (St. Louis, MO).…”

“…We also synthesized a stable PGE 1 prodrug (Δ 8 -9-Obutyryl prostaglandin F 1 butyl ester, AS-013) and lipo-AS-013 showed superior characteristics to lipo-PGE 1 in both animal and clinical studies (6,16,17). However, lipid microspheres cannot retain PGE 1 for a long period of time in vivo (16,18). Therefore, daily intravenous drip infusion is necessary for clinical treatment with lipo-PGE 1 , which in turn requires patient hospitalization, resulting in a low quality of life (QOL).…”

“…One obstacle to the use of solid nanoparticles in the treatment of patients in clinical practice is the uptake of these particles by the mononuclear phagocyte system (MPS), or in other words by the reticuloendothelial system (21,24). Use of a monomethoxy poly (ethyleneglycol)-PLA block copolymer (PEG-PLA) enables the nanoparticles to escape from this uptake due to the steric barrier by which the PEG chain prevents interaction of the nanoparticles with opsonins and cells responsible for MPS, such as Kupffer cells (stealth effect) (18,21,24). Another obstacle is that relatively hydrophilic drugs, such as PGE 1 and betamethasone, are very hard to encapsulate in PLA-nanoparticles (25)(26)(27).…”