Mild Hyperthermia Responsive Liposomes for Enhanced In Vitro and In Vivo Anticancer Efficacy of Doxorubicin against Hepatocellular Carcinoma

Abstract

The current study is aimed to fabricate doxorubicin (Dox) loaded mild temperature responsive liposomes (MTLs) by thin film hydration technique for enhanced in vitro and in vivo anticancer efficacy against hepatocellular carcinoma. The aforementioned Dox loaded MTLs were developed and optimized with extrusion and drug loading techniques. The optimized MTLs were in optimum size range (118.20 ± 2.81–187.13 ± 4.15 nm), colloidal stability (−13.27 ± 0.04 to −32.34 ± 0.15 mV), and enhanced entrapment of Dox (28.71 ± 2.01–79.24 ± 2.16). Furthermore, the optimized formulation (MTL1-E(AL)) embodied improved physicochemical stability deducted by Fourier transform infra-red (FTIR) spectroscopy and mild hyperthermia-based phase transition demonstrated from differential scanning calorimetry (DSC). An in vitro drug release study revealed mild hyperthermia assisted rapid in vitro Dox release from MTLs-E(AL) (T100% ≈ 1 h) by Korsmeyer–Peppas model based Fickian diffusion (n < 0.45). Likewise, an in vitro cytotoxicity study and lower IC50 values also symbolized mild hyperthermia (40.2 °C) based quick and improved cytotoxicity of MTL1-E(AL) in HepG2 and MCF-7 cells than Dox. The fluorescence microscopy also represented enhanced cellular internalization of MTL1-E(AL) at mild hyperthermia compared to the normothermia (37.2 °C). In addition, an in vivo animal study portrayed the safety, improved anticancer efficacy and healing of hepatocellular carcinoma (HCC) through MTL1-E(AL). In brief, the Dox loaded MTLs could be utilized as safe and effective therapeutic strategy against HCC.

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells

“…It is worth noting that, although a negatively charged surface might slightly affect the cellular internalization, the stability of nano-systems against aggregation is crucial for benefiting from the nano-size. In addition, many studies have reported enhanced anticancer activity for negatively charged nanoformulation [ 44 , 45 , 46 , 47 ]. Accordingly, the study aimed at maximizing the absolute ZP value.…”

Interventional nanotheranostics in hepatocellular carcinoma

“…For the pictorial presentation, refer Figure 3 . Moreover, ThermoDox with RFA therapy produces a high drug concentration of doxorubicin as compared to free doxorubicin near the ablation zone due to hyperthermia 119 , 120 , 121 .…”

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

“…Then, the lipid film was hydrated using cisplatin solution in phosphate-buffered saline (pH 7.4) (5.0 mg/10 mL). The resultant liposomal suspension was vortexed and sonicated (ELMA, E-30 H, Pforzheim, Germany) for about 10 min (at 25 • C and an amplitude of 30%), and then extruded through polycarbonate-membrane-based mini extruders (100 nm, Nano-sizer Mini ® , T&T scientific corporations, Knoxville, TN, USA) to obtain the liposomes for further analysis [19]. The particle size, PDI and zeta potential of the developed CDDP@PLs were analyzed using Zeta Sizer-ZS90 (Malvern, Worcestershire, UK).…”

“…The FTIR spectra of DOPE (Figure 2c) showed characteristic peaks at 1455 cm −1 (-CH bending), 1706 cm −1 (-C=O stretching), 2853 cm −1 (-OH stretching) and at 2922 cm −1 (-NH stretching). The FTIR spectra of DSPE-PEG 2000 (Figure 2d) showed characteristic peaks at 2855 cm −1 (-CH stretching of alkane), 1522 cm −1 (N-O stretching) and at 1103 cm −1 (P=O stretching) [19,36], whereas the FTIR spectra of the CDDP@PLs (Figure 2e) showed characteristics peaks at 1252 cm −1 (1263 cm −1 of cisplatin due to symmetric amine bending), 1527 cm −1 (1540 cm −1 of cisplatin due to asymmetric amine bending), 1729 cm −1 (1731 cm −1 of CHEMS due to -C=O stretching vibration of ester and carboxyl group), 2872 cm −1 (2853 cm −1 of DOPE due to -OH stretching), and at 2939 cm −1 (2963 cm −1 due to -OH stretching vibration and out-of-plane bending vibration of the carboxyl group of CHEMS or due to 2966 cm −1 of cisplatin because of amine stretching). All the characteristic peaks of cisplatin were present in the liposomal formulation, indicating the compatibility of cisplatin and formulation components.…”