Evaluation of the potential of doxorubicin loaded microbubbles as a theranostic modality using a murine tumor model

Abstract

In this study, a novel phospholipid-based microbubble formulation containing doxorubicin and perfluoropropane gas (DLMB) was developed. The DLMBs were prepared by mechanical agitation of a phospholipid dispersion in the presence of perfluoropropane (PFP)gas. An anionic phospholipid, distearoylphosphatidylglycerol (DSPG) was selected to load doxorubicin in the microbubbles by means of electrostatic interaction. The particle size, zeta potential, echogenicity and stability of the DLMBs were measured. Drug loading was ≥92%.The potential of the DLMBs for use as a theranostic modality were evaluated in tumor bearing mice. Gas chromatography analysis of PFP showed significant enhancement of PFP retention when doxorubicin was used at concentrations of 10-82% equivalent to DSPG. The inhibitory effects on the proliferation of B16BL6 melanoma murine cells in vitro were enhanced using a combination of ultrasound (US) irradiation and DLMBs. Moreover, in vivo DLMBs in combination with (US) irradiation significantly inhibited the growth of B16BL6 melanoma tumor in mice. Additionally, US echo imaging showed high contrast enhancement of the DLMBs in the tumor vasculature. These results suggest that DLMBs could serve as US triggered carriers of doxorubicin as well as tumor imaging agents in cancer therapy.

One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin

“…Blood was taken from the inferior vena cava, and the heart, liver, spleen, lung and kidney were harvested and weighed. Dox and Cur were extracted as reported in a previous study (Abdalkader et al, 2015). Briefly, organs were homogenised using a mixed solution of isopropanol and 1 M HCl (1:1, v/v) and incubated at 4°C for 1 h. The solutions were centrifuged at 1,630 × g for 15 min, and the supernatants were centrifuged again at 15,000 × g for 15 min.…”

Chitosan-coated microvesicles: Effect of polysaccharide-phospholipid affinity on decafluorobutane dissolution

“…Although the impact of chitosan in the resultant surface tension and Laplace pressure towards the decafluorobutane core as well as shell elasticity behavior in gaseous environments still need to be elucidated, this new composite interface was effective in reducing the C 4 F 10 dissolution dynamics compared to a commonly employed phospholipid shell. Similar composite monolayers of phospholipid mixture intercalated with doxorubicin were also effective in reducing perfluoropropane (C 3 F 8 ) lost along the time, with dependency on drug rate incorporation into the shell (Abdalkader et al, 2015).…”

“…Lipid-coated microvesicles containing a perfluorocarbon gas core are widely employed as ultrasound contrast agents (UCA) in clinical imaging and targeted-release systems of therapeutic agents (Abdalkader et al, 2015;Ferrara, Borden, & Zhang, 2009). Although UCA utilization is recommended in several cardiology assays, the current gas-filled microvesicles generation exhibits low gas permeation resistance and short circulation lifetime (Garg, Thomas, & Borden, 2013;Wilson & Burns, 2010).…”

The development of mechanically formed stable nanobubbles intended for sonoporation-mediated gene transfection

“…We have previously reported that MBs loaded with doxorubicin can only be stably prepared with the mechanical agitation method (Abdalkader et al, 2015). During the mechanical agitation method, no significant temperature elevation is generated, which is useful for thermosensitive materials.…”