Engineering the lipid layer of lipid–PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability

Abstract

Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long- term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement.

The next-generation nicotine vaccine: a novel and potent hybrid nanoparticle-based nicotine vaccine

“…As illustrated in Scheme 1, NanoNiccine was assembled by conjugating nicotine haptens to the surface of previously well characterized lipid-PLGA hybrid nanoparticles [20]. The morphology and structure of NanoNiccine were investigated by CLSM and TEM.…”

“…The whole process and components appeared to be complex, but each step was easy to perform. Moreover, according to previous studies [20, 40], the physicochemical properties of the vaccine particles were controllable. Lipid-PLGA hybrid nanoparticle has proven to be an excellent delivery system for vaccines and anti-cancer drugs [41].…”

“…Both CLSM and TEM images of NanoNiccine confirmed the formation of the hybrid structure. In our previous studies [20, 40], it was found that the hybrid structures of lipid-PLGA nanoparticles can be built via sonication mediated fusion, which was used in this study. Moreover, the hybrid nanoparticles proved to be highly stable under physiological conditions over time [40].…”

“…[20, 22] The lipid film containing 0.25 mg MPLA, 2.83 mg DOTAP, 3.08 mg (DSPE-PEG2000) carboxylic acid, and 0.1 mg cholesterol was hydrated with 1 mL of 55 °C pre-warmed PBS buffer. The resulting liposome suspension was vigorously mixed using a vortex mixer for 2 min, followed by sonication for 5 min, using a Branson B1510DTH Ultrasonic Cleaner (Branson, Danbury, CT) and then cooled to room temperature.…”

CS/PAA@TPGS/PLGA nanoparticles with intracellular pH-sensitive sequential release for delivering drug to the nucleus of MDR cells

“…Vitamin E d-a-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles (TPGS/PLGA NPs) are another type of nanoparticle with pH-sensitive release properties. TPGS/PLGA NPs can release contained substances in acidic pH environments and remain stable at physiological pH values [18][19][20][21]. However, entry of TPGS/PLGA NPs into the nucleus is limited by the diameter of the nuclear pore.…”