Modifying Cationic Liposomes with Cholesteryl-PEG Prevents Their Aggregation in Human Urine and Enhances Cellular Uptake by Bladder Cancer Cells

Abstract

Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs. When 2 mol% of PEG2k lipids were introduced, the lipid structures of 1,2-distearoly-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-distearoyl-snglycerol (DSG) greatly prevented aggregation compared with cholesterol. By contrast, when Cat-LPs, after incubation in urine, were exposed to bladder cancer cells, only introducing cholesteryl-PEG into the CatLPs showed a significant enhancement in cellular uptake. These results offer the potential for incorporating cholesteryl-PEG into Cat-LPs for achieving both stability in urine and effective cellular uptake.

Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives

“…For example, the changes of the tonicity of the nasal environment may considerably affect the liposomal formulation stability and the drug-releasing rate [51]. Formulations that can minimize the particle aggregation at nasal pH would be required to ensure the intranasal stability of liposomes, as cationic liposomes are prone to aggregation in physiological conditions [88]. Setting reliable in vitro or ex vivo study models that can test the impact of these formulation factors would be essential for facilitating the development of liposome formulations for nose-to-brain delivery.…”

Effects of PEG anchors in PEGylated siRNA lipoplexes on in�vitro gene‑silencing effects and siRNA biodistribution in mice

“…in addition, PeG-dMG dissociated rapidly from PeGylated lipid nanoparticle-encapsulated sirna, but PeG-dSG dissociated slowly (11). Furthermore, incorporation of PeG-chol into cationic liposomes was stabilized in human urine and enhanced cellular uptake, whereas the incorporation of PeG-dSPe or PeG-dSG into cationic liposomes effectively prevented the formation of agglomeration but decreased cellular uptake (12). These findings suggested that anchors of PeG derivatives in PeGylated sirna lipoplexes strongly affected cellular association and stability in the blood circulation.…”

Potential Applications of Nanotechnology in Urological Cancer

“…To improve the poor solubility and enhance the efficiency of the cell wall skeleton (CWS) of BCG, Nakamura’s group encapsulated the CWS of BCG within liposomes ( Nakamura et al, 2014 ). Recently, they modified cationic liposomal surfaces with cholesteryl-PEG to overcome urine aggregation and promote cellular uptake into cancerous urothelial tissues ( Nakamura et al, 2017 ). Liposomes can be also used to envelop small interfering RNA (siRNA) silencing oncogenes or other tumor-related genes for the prevention or treatment of BCa.…”