Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imaging

Abstract

In numerous studies, liposomes have been used to deliver anticancer drugs such as doxorubicin to local heat-triggered tumor. Here, we investigate: (i) the ability of thermosensitive liposomal nanoparticle (TSLnp) as a delivery system to deliver poorly membrane-permeable anticancer drug, gemcitabine (Gem) to solid pancreatic tumor with the aid of local mild hyperthermia and, (ii) the possibility of using gadolinium (Magnevist®) loaded-TSLnps (Gd-TSLnps) to increase magnetic resonance imaging (MRI) contrast in solid tumor. In this study, we developed and tested gemcitabine-loaded thermosensitive liposomal nanoparticles (Gem-TSLnps) and gadolinium-loaded thermosensitive liposomal nanoparticles (Gd-TSLnps) both in in-vitro and in-vivo. The TSLnps exhibited temperature-dependent release of Gem, at 40–42°C, 65% of Gem was released within 10 min, whereas < 23% Gem leakage occurred at 37°C after a period of 2 h. The pharmacokinetic parameters and tissue distribution of both Gem-TSLnps and Gd-TSLnps were significantly greater compared with free Gem and Gd, while Gem-TSLnps plasma clearance was reduced by 17-fold and that of Gd-TSLpns was decreased by 2-fold. Area under the plasma concentration time curve (AUC) of Gem-TSLnps (35.17± 0.04 μghr/mL) was significantly higher than that of free Gem (2.09 ± 0.01 μghr/mL) whereas, AUC of Gd-TSLnps was higher than free Gd by 3.9 fold high. TSLnps showed significant Gem accumulation in heated tumor relative to free Gem. Similar trend of increased Gd-TSLnps accumulation was observed in non-heated tumor compared to that of free Gd; however, no significant difference in MRI contrast enhancement between free Gd and Gd-TSLnps ex-vivo tumor images was observed. Despite Gem-TSLnps dose being half of free Gem dose, antitumor efficacy of Gem-TSLnps was comparable to that of free Gem(Gem-TSLnps 10 mg Gem/kg compared with free Gem 20 mg/kg). Overall, the findings suggest that TSLnps may be used to improve Gem delivery and enhance its antitumor activity. However, the formulation of Gd-TSLnp needs to be fully optimized to significantly enhance MRI contrast in tumor.

Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models

“…After the injection, aliquots of blood samples were collected at predetermined time points (5, 10, 15, 30, 60, 120, 240, 360, 720 and 1440 min). Blood samples collected were treated with 2 mL of an extraction solvent (15% of isopropyl alcohol in ethyl acetate) ( Beumer et al, 2008 ; Affram et al, 2017 ). The mixture was vortexed for 30 s and centrifuged at 3000 rpm for 15 and the supernatant collected and vaporized to dry overnight in a water-bath.…”

Cellular viability and osteogenic differentiation potential of human gingiva‑derived stem cells in 2D culture following treatment with anionic, cationic, and neutral liposomes containing doxorubicin

“…In numerous previous studies, liposomes have been used to deliver anti-cancer drugs, including doxorubicin, to local tumors ( 5 ). Liposomal doxorubicin along with conventional doxorubicin has potential risks of causing adverse events, including myelosuppression, cardiotoxicity, alopecia, nausea and vomiting ( 6 ).…”

Comparative study on contrast enhancement of Magnevist and Magnevist-loaded nanoparticles in pancreatic cancer PDX model monitored by MRI

“…Mag-Lnps phantoms were prepared as described by others (Affram et al 2017;Agyare et al 2014). In brief, Mag-Lnps solution was diluted by thoroughly mixing it with distilled water in a ratio of 1:1, 1:5, 1:10 and 1:100.…”