Résumé
Objective: In this study we prepared a novel formulation of liposomal doxorubicin [L-DOX]. The drug dose was optimized by analyses of cellular uptake and cell viability of osteosarcoma [OS] cell lines upon exposure to nanoliposomes that contained varying DOX concentrations. We intended to reduce the cytotoxicity of DOX and improve characteristics of the nanosystems
Materials and Methods: In this experimental study, we prepared liposomes by the pH gradient hydration method. Various characterization tests that included dynamic light scattering [DLS], cryogenic transmission electron microscopy [Cryo-TEM] imaging, and UV-Vis spectrophotometry were employed to evaluate the quality of the nanocarriers. In addition, the CyQUANT[registered] assay and fluorescence microscope imaging were used on various OS cell lines [MG-63, U2-OS, SaOS-2, SaOS-LM7] and Human primary osteoblasts cells, as novel methods to determine cell viability and in vitro transfection efficacy
Results: We observed an entrapment efficiency of 84% for DOX within the optimized liposomal formulation [L-DOX] that had a liposomal diameter of 96 nm. Less than 37% of DOX released after 48 hours and L-DOX could be stored stably for 14 days. L-DOX increased DOX toxicity by 1.8-4.6 times for the OS cell lines and only 1.3 times for Human primary osteoblasts cells compared to free DOX, which confirmed a higher sensitivity of the OS cell lines versus Human primary osteoblasts cells for L-DOX. We deduced that L-DOX passed more freely through the cell membrane compared to free DOX
Conclusion: We successfully synthesized a stealth L-DOX that contained natural phospholipid by the pH gradient method, which could encapsulate DOX with 84% efficiency. The resulting nanoparticles were round, with a suitable particle size, and stable for 14 days. These nanoparticles allowed for adequately controlled DOX release, increased cell permeability compared to free DOX, and increased tumor cell death. L-DOX provided a novel, more effective therapy for OS treatment
Sujets)
Humains , Polyéthylène glycols , Systèmes de délivrance de médicaments , Ostéosarcome , Lignée cellulaire tumorale , Lignée cellulaireRésumé
Objective: This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma [HCC] cell line [HepG2]
Materials and Methods: In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude. Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine [DPPC], cholesterol [CHOL], and methoxy-polyethylene glycol 2000 [PEG2000]-derived distearoyl phosphatidylethanolamine [mPEG2000-DSPE]. We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin [25% w/v] and glycyrrhizic acid [75% w/v] on HepG2 and fibroblast cell lines over a 48-hour period
Results: Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency [EE] for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results of in vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration [IC50] for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 microg/ml and free silibinin with glycyrrhizic acid was 485.45 microg/ml on the HepG2 cell line
Conclusion: This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line