Comparative studies of irinotecan-loaded polyethylene glycol-modified liposomes prepared using different PEG-modification methods

Abstract

Recently, a polyethylene glycol (PEG)-modification method for liposomes prepared using pH-gradient method has been proposed. The differences in the pharmacokinetics and the impact on the antitumor effect were examined; however the impact of PEG-lipid molar weight has not been investigated yet. The main purpose of this study is to evaluate the impact of PEG-lipid molar weight against the differences in the pharmacokinetics, the drug-release profile, and the antitumor effect between the proposed PEG-modification method, called the post-modification method, and the conventional PEG-modification method, called the pre-modification method. Various comparative studies were performed using irinotecan as a general model drug. The results showed that PEG-lipid degradation could be markedly inhibited in the post-modification method. Furthermore, prolonged circulation time was observed in the post-modification method. The sustained drug-release was observed in the post-modification method by the results of the drug-releasing test in plasma. Moreover, a higher antitumor effect was observed in the post-modification method. It was also confirmed that the same behaviors were observed in all comparative studies even though the PEG molecular weight was lower. In conclusion, the post-modification method has the potential to be a valuable PEG-modification method that can achieve higher preservation stability of PEG-lipid, prolonged circulation time, and higher antitumor effect with only half the amount of PEG-lipid as compared to the pre-modification method. Furthermore, it was demonstrated that PEG(5000)-lipid would be more desirable than PEG(2000)-lipid since it requires much smaller amount of PEG-lipid to demonstrate the same performances.

Folic‐Acid‐Mediated Functionalized Gold Nanocages for Targeted Delivery of Anti‐miR‐181b in Combination of Gene Therapy and Photothermal Therapy against Hepatocellular Carcinoma

“…This result was due to the prolonged circulation time induced by PEG conjugated on the surface of AuNC-NPs, as previously reported. [39][40][41] These observations indicate that the FA-mediated targeted PTPAuNC-NPs facilitated the accumulation of gene drugs in tumors, compared with naked anti-miR-NC and passive targeted formulation, PPAuNC-NPs.…”

Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

“…These two approaches are currently used in clinically approved formulations [44]. Postinsertion of DSPE-PEG2000 compared to its preinsertion in irinotecan-loaded liposomes revealed higher plasma concentration and slower drug release in rats [60]. Of note, this longer blood circulation time was correlated with better therapeutic efficacy of postinserted DSPE-PEG2000 drug-loaded liposomes.…”

“…This results in decreased drug loading and stealth properties of the liposomes. Indeed, when both strategies of PEGylation were compared, higher blood circulation and higher therapeutic efficacy in vivo of postinsertion over preinsertion modification were demonstrated [60, 61]. …”

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

“…[16][17][18][19][20] The issue of micelle contamination and controlling the orientation of the anchors are major impediments to such an evaluation. Currently, three methods are in widespread use for modifying the liposomal surface.…”