Micelle-contained and PEGylated hybrid liposomes of combined gemcitabine and cisplatin delivery for enhancing antitumor activity

Combination, synergistic chemotherapy with gemcitabine (GEM) and cisplatin (CDDP) is a common strategy, and has been recommended for tumor treatment due to its promoted therapeutic effect and reduced systemic toxicity. However, this process involves the intravenous infusion of GEM prior to that of CDDP, which is inconvenient for patients and staff. Here, a novel hybrid nano-carrier system comprised of micelles encapsulated within PEGylated liposomes is proposed, in order to combine the unique strengths of each component. CDDP was bonded with PLGPEG, and then the formed CDDP@PLG-PEG micelles and GEM were co-loaded inside PEGylated liposomes. The hybrid liposomes with the optimized GEM/CDDP ratio (1:0.6) showed a roughly spherical morphology, appropriate drug loading, and sustained release behavior. In vitro, the hybrid liposomes had 1.72-fold increased cellular uptake, and 57.42%-fold decreased IC50 value. In vivo, pharmacokinetic studies showed increased t1/2 values (125.64%- and 128.57%-folds for GEM and CDDP), decreased clearance (41.90%- and 2.37%-folds), and promoted AUC (262.76%- and 4577.24%-folds). Finally, an in vivo antitumor study showed effective activity in regards to lung tumor size and weight, which were 40.48%- and 33.11%-folds that of GEM/CDDP solution. In summary, we demonstrated the development of an effective micelle-containing PEGylated hybrid liposomes for combined GEM/CDDP delivery.

Automated summary

A novel hybrid nano-carrier system composed of micelles encapsulated within PEGylated liposomes was developed to combine the unique strengths of each component for combined delivery of GEM and CDDP. The hybrid liposomes showed enhanced cellular uptake and decreased IC50 value in vitro, as well as improved pharmacokinetic properties and antitumor efficacy in vivo. This study demonstrated the potential of the micelle-containing PEGylated hybrid liposomes for synergistic chemotherapy with GEM and CDDP.