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

Abstract

Abstract. Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also discounted. The aim of this study is to develop a long-circulating prostaglandin E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1 nanoemulsion was prepared using a dispersing-homogenized method. The stability of nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed to evaluate the in vivo profile of the optimized nanoemulsion. The optimized nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a surface charge of −14 mV. Approximately, 97% of the PGE1 was encapsulated in the nanoemulsion. The particle size, zeta potential, and drug loading of PGE1-PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was intravenously administered to rats, the area under curve (AUC) and half-life of PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1 (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for prolonging the elimination time of PGE1. This novel parenteral colloidal delivery system of PGE1 has a promising potential in clinic use.

Preparation of Prolonged-Circulating Galangin-Loaded Liposomes and Evaluation of Antitumor Efficacy In Vitro and Pharmacokinetics In Vivo

“…Liposomes carry a small negative charge, which hinders aggregation and fusion and increases stability [20]. PEG-modified liposomes have a more negative zeta potential, possibly due to the presence of a negatively charged phosphate group, as previously reported [21].…”

Date Palm Extract (Phoenix dactylifera) PEGylated Nanoemulsion: Development, Optimization and Cytotoxicity Evaluation

“…It was detected that (NNE) showed a particle size 260 ± 5.5 nm and (PDI) 0.22 which is regarded as a higher value if compared to that of PEG-NE that recorded particle size 159.33 ± 3.4 with (PDI) 0.25 as presented in Figure 7 C,D. This finding could suggest the upshot of PEGylation on particle size and the homogeneity of the NE formulation whereas uniformity of particle size has a great impact on the therapeutic efficiency of the formulation [ 45 ]. Regarding zeta potential, PEGylated NEs demonstrated a decline in the negative charge of the formulation surface (3.23 ± 0.26) compared to their naked counterpart (−24.6 ± 0.51) which is ascribed to the coating of the surface by PEG [ 46 ].…”

A Nano-Emulsion Platform Functionalized with a Fully Human scFv-Fc Antibody for Atheroma Targeting: Towards a Theranostic Approach to Atherosclerosis

“…To our knowledge, only a few studies have investigated how to prolong the half-life of PEGylated NEs [ 30 , 51 , 52 ]. Cheng et al studied how different molecular weights and different concentrations of lipid–PEG affected NE size but did not analyze their pharmacokinetic profiles [ 52 ]. Hak et al studied the influence of lipid–PEG 2000 density on NE pharmacokinetics by fluorescence analysis of animal serum samples [ 53 ].…”