Surface Distribution and Biophysicochemical Properties of Polymeric Micelles Bearing Gemini Cationic and Hydrophilic Groups

Abstract

Polymeric micelles containing cationic gemini quaternary ammonium (GQA) groups have shown enhanced cellular uptake and efficient drug delivery, while the incorporation of poly(ethylene glycol) (PEG) corona can potentially reduce the absorption of cationic carriers by opsonic proteins and subsequent uptake by mononuclear phagocytic system (MPS). To understand the interactions of GQA and PEG groups and their effects on the biophysicochemical characteristics of nanocarriers, a series of polyurethane micelles containing GQA and different molecular weights of PEG were prepared and carefully characterized. It was found that the GQA and PEG groups are unevenly distributed on the micellar surface to form two kinds of hydrophilic domains. As a result, the particle surface with some defects cannot be completely shielded by the PEG corona. Despite this, the longer PEG chains with a brush conformation provide superior stabilization and steric repulsion against the absorption of proteins and, thus, can reduce the cytotoxicity, protein absorption, and MPS uptake of micelles to some extent. This study provides a new understanding on the interactions between PEG chains and cationic groups and a guideline for the design and fabrication of safe and effective drug delivery systems.

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

“…According to literatures, upon interaction with serum, nanocarriers rapidly absorbed protein and formed a corona ( Bertrand et al, 2017 ; Pan et al, 2017 ). It was the nanocarrier–corona complex, rather than the nanocarrier, that interacted with biological systems, here with a cell membrane receptor (CD206), which might partially obscure the role of target ligands ( Monopoli et al, 2012 ).…”

Stable, Bioresponsive, and Macrophage-Evading Polyurethane Micelles Containing an Anionic Tripeptide Chain Extender

“…A series of anionic polyurethanes were synthesized from l -lysine diisocyanate (LDI), mPEG, cystine, CYSD, and PCL according to our previous report. 45 Briefly, pre-polymerization of LDI and PCL was carried out in the presence of 0.1% stannous octoate catalyst and under the protection of nitrogen at 60 °C for 1 h. The resulting solution was cooled down to room temperature, after which the chain extender CYSD and tripeptide were added to react at room temperature for 1 h (for T0C50mE1900, the addition of 1,3-propanediol (PDO) is needed to react at 80 °C for an extra 2 h). Subsequently, mPEG as the terminated chain was added and reacted at 90 °C for 6 h. The final products were precipitated by diethyl ether and washed at least three times, after which the products were dried under vacuum at 50 °C for 2 days.…”

Engineered Polymeric Materials for Biological Applications: Overcoming Challenges of the Bio–Nano Interface

“…With new approaches rapidly being developed and our knowledge of these systems improving, new strategies for avoiding specific components or controlling this process are regularly being reported. Many nanomedicine adaptations have been generated through pre-incubation with serum [39] and artificial creation of the hard corona [40], whereas others have used polymer design to modulate protein corona [41]. The research into improving the interactions with this barrier also suggest some of the most customizable approaches are attractive for further investigation.…”