Effects of gelucire content on stability, macrophage interaction and blood circulation of nanoparticles engineered from nanoemulsions

The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water nanoemulsion precursors were prepared using binary mixtures of CA and gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes of gelucire-based NPs (128–183 nm) were five times lower than control NPs (made without gelucire). All the NPs (with or without gelucire component) did not activate macrophages as monitored by reactive oxygen species production. Results from differential scanning calorimetry, FT-IR and multimodal light scattering measurements demonstrated the involvement of gelucire component in achieving homogeneous CA/gelucire particle populations that were stable on storage. The P-glycoprotein (P-gp) function assay in MES-Dx5 cells showed the potential of gelucire-based NPs in inhibiting rhodamine 123 efflux. Similarly, the extent of NP uptake by macrophage (RAW 264.7 cell) was dependent on the amount of gelucire component (inverse relationship; R2 = 0.996). NPs made with CA/gelucire mixture (at 50%, w/w gelucire) were the most effective in blood circulation studies in BALB/c mice. Additional studies with paclitaxel-loaded NPs demonstrated that the retention of gelucire-based NPs in blood circulation was comparable to NPs coated with DSPE-PEG2000 (p > 0.6). The over-all work indicated the potential efficacy of gelucire as a safe and biocompatible excipient that can serve multiple functions in enhancing the performance of lipid-based NP drug delivery systems.

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► Stable nanoparticles were prepared from gelucire/cetyl alcohol binary mixtures.
► Nanoparticles did not activate macrophages.
► Increasing gelucire content on nanoparticle caused a reduction in phagocytosis.
► Inhibition of P-glycoprotein efflux was attributed to gelucire effect.
► Gelucire was effective in prolonging nanoparticle blood circulation times.