Characterization of PLGA Nanospheres Stabilized with Amphiphilic Polymers: Hydrophobically Modified Hydroxyethyl Starch vs Pluronics

Abstract

Some Pluronics, particularly F127, are known to stabilize nanospheres and prolong their circulation time in vivo. However, these copolymers of poly(ethylene glycol) (PEG) and poly(propylene glycol) are not biodegradable, and despite the long history, there is no approved commercial product using F127 for parenteral administration until now. Meanwhile, hydroxyethyl starch (HES) is a biodegradable polymer that is currently investigated as a substitute for PEG. In order to produce a fully biodegradable amphiphilic polymer, we esterified different molar masses of HES with lauric acid to get different molar substitutions. These polymers, as well as Pluronic F68 and F127, were used to stabilize poly(lactic-co-glycolic acid) (PLGA) nanospheres prepared by nanoprecipitation. For physicochemical characterization, the particle size, zeta potential, and the thickness of the adsorbed polymer layer were measured. The ability of the polymer coating to prevent the adsorption of human serum albumin (HSA) and fibrinogen (FBG) was evaluated. Finally, the phagocytosis of the stabilized nanospheres by a monocyte macrophage cell line (J774.2) was assessed. Results show that the PLGA nanospheres had an average particle size of 110-140 nm. The thickness of the adsorbed polymer layer increases with the increase in molar mass, and is generally higher for HES laurates than the studied Pluronics. Pluronic F68, F127 as well as the HES laurates with low molar substitution prevented the adsorption of HSA. HES laurates with low molar substitution and F127, but not F68, prevented the adsorption of FBG. The phagocytosis experiments showed that the HES laurates, particularly the one with the highest molar mass, could reduce the uptake of the nanospheres better than F68 and comparable to F127. Finally, these results warrant in vivo experiments to evaluate how the HES laurates can affect the pharmacokinetics and fate of the nanospheres.

The combined use of paclitaxel-loaded nanoparticles with a low-molecular-weight copolymer inhibitor of P-glycoprotein to overcome drug resistance

“…[14][15][16][17] However, the potential drawback of using Pluronics is the nondegradability and lack of renal excretion for high-molecular-weight members of this copolymer class. 18,19 Previous work by our group has demonstrated that a very low-molecular-weight MePEG-b-PCL copolymer (MePEG 17 -b-PCL 5 [PCL5]) is an effective modulator of P-gp. We reported on the ability of PCL5 used at concentrations above and below the critical micelle concentration (0.03%) to enhance the accumulation of Pgp substrates, including PTX, in P-gp-overexpressing cell.…”

Preparation, optimization, and in vitro simulated inhalation delivery of carvedilol nanoparticles loaded on a coarse carrier intended for pulmonary administration

“…The decrease in ZP with an increase in the thickness of the adsorbed polymer layer is due to the outward shift of the slipping plane, at which ZP is measured. 50 According to Gouy-Chapman theory, the slipping plane is moved to a point further out from the surface where the charge density is much smaller than on the surface resulting in lower ZP. This explains the lower ZP (as an absolute value) of Pluronic F127 nanosuspensions (having higher thickness of adsorbed polymer layer due to higher number of PEO units) compared with Pluronic F68 nanosuspensions (Table 1; Figure 3C).…”

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin

“…Differences observed between F68 and F127 could also be related to the small molecular weight of the PEG chains presented in F68 (approximately 4000 g/mol for F68 and 5000 g/mol for F127). In other studies, F68-coated particles shown higher uptake by macrophages when compared to F127-coated particles (60,61). Regarding F108 micelles, size appears to be the main responsible for the higher uptake compared to F127 micelles.…”