Diminishing the side effect of mitomycin C by using pH-sensitive liposomes: in vitro characterization and in vivo pharmacokinetics

Abstract

IntroductionMitomycin C is an anticancer antibiotic agent that has the potential for broad-spectrum use against several cancers, including mammary cancers. Because its half-life is 17 min after a 30 mg intravenous bolus administration, the suitability of mitomycin C for wide use in the clinical setting is limited. Based on tumor pathophysiology, pH-sensitive liposomes could provide better tumor-targeted effects. The aim of this study was to investigate the possibility of diminishing the side effect of mitomycin C by using pH-sensitive liposomes.Materials and methodspH-sensitive liposomes was employed to deliver mitomycin C and evaluate the characterization, release behaviors, cytotoxicity, in vivo pharmacokinetics and biochemical assay.ResultsThe results demonstrated that mitomycin C-loaded pH-sensitive liposomes had a particle diameter of 144.5±2.8 nm and an entrapment efficiency of 66.5%. The in vitro release study showed that the pH-sensitive liposome release percentages at pH 7.4 and pH 5.5 were approximately 47% and 93%, respectively. The cell viability of MCF-7 cells showed that both the solution and liposome group exhibited a concentration-dependent effect on cell viability. The MCF-7 cell uptake of pH-sensitive liposomes with a folate modification was higher which was indicated by an increased fluorescence intensity compared to that without a folate modification. The area under the concentration–time curve of mitomycin C-loaded pH-sensitive liposomes (18.82±0.51 µg·h/L) was significantly higher than that of the mitomycin C solution group (10.07±0.31 µg·h/L). The mean residence times of the mitomycin C-loaded and mitomycin C solution groups were 1.53±0.16 and 0.05 h, respectively. In addition, there was no significant difference in terms of Vss (p>0.05). Moreover, the half-life of pH-sensitive liposomes and the mitomycin C solution was 1.35±0.15 and 1.60±0.04 h, respectively. In terms of safety, mitomycin C-loaded pH-sensitive liposomes did not affect the platelet count and the levels of blood urea nitrogen and aspartate aminotransferase.ConclusionThe positive results of pH-sensitive liposomes demonstrated maintained the cytotoxicity and decrease the side effect.

Anti-EGFR Indocyanine Green-Mitomycin C-Loaded Perfluorocarbon Double Nanoemulsion: A Novel Nanostructure for Targeted Photochemotherapy of Bladder Cancer Cells

“…The change of the emulsion configuration may subsequently reach an equilibrium state, and hence the drug release rate was decreased. Moreover, in comparison with other, similar products reported previously, the release efficiency of the MMC from the EIMPDNEs is lower than that released from the liposome [ 39 ], micelle [ 40 ], and polymeric [ 41 ] nanostructures, implying that the MMC is relatively stable in the EIMPDNEs. We speculate that the moderated drug release rate of the EIMPDNE can be attributed to (1) less reactivity of the nanodroplets because the electrostatic repulsion generated from the surface charge may diminish their interactions with foreign molecules and/or each other, conferring an enhanced shelf stability to the EIMPDNEs in an aqueous medium, and (2) a higher degree of steric hindrance on the emulsion surface that is caused by a tangled PEO-PPO-PEO copolymer and/or antibody molecules.…”

Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

“…A second series of pH-sensitive nanoformulations (F5, F6 and F7) was developed to explore Cuphen release at the slightly acidic tumour microenvironment [28,29]. To attain this goal, CHEMS was included in the lipid composition since, when in contact with an acidic milieu, it becomes protonated, leading to bilayer disruption and subsequent drug release [29,[39][40][41].…”

“…Tumours' microenvironment, as in the case of melanoma, is slightly acidic, presenting pH values around 6, in contrast to the normal physiological pH of 7.4 [28,29], which heavily impacts cancer development [47,48], and it can be explored as stimuli for triggering local liposomal drug release. In the current work, we developed long circulating pH-sensitive nanoliposomes by including CHEMS in the lipid composition [29,[39][40][41]. To validate pH-sensitive properties of F6, the quantification of the metallodrug still associated to nanoliposomes was assessed upon exposure to different pH conditions.…”

Atrial natriuretic peptide modified oleate adenosine prodrug lipid nanocarriers for the treatment of myocardial infarction: in vitro and in vivo evaluation

“…This difference may be due to the ANP modification on the surface of LNCs hindered the drug release. 38 The reason behind this sustained release behavior is attributed to slow degradation of the nanomaterials, and drugs were diffused from the matrix in a sustained manner. Moreover, the PEG shell on the outside of carriers also protects the drugs and let them have longer release time.…”