Page 172 - Read Online

Dastidar et al. Vessel Plus 2020;4:14 I http://dx.doi.org/10.20517/2574-1209.2019.36 Page 19 of 29

A B

Figure 5. Schematic representation of cancer treatment with anticancer drug-loaded liposome-micro-bubble complexes (PLMC)
assisted by ultrasound (US). A: when flowing through the target region, drugs remain attached to the lipid shells of MBs but are unable
to cross the tumour vasculature by simple diffusion; B: application of high-intensity focused US bursts the micro-bubbles to release
drugs. The cavitating and imploding MBs also enhance permeability of the plasma membrane, leading to higher uptake of released
drugs. MBs: micro-bubbles

Theek et al. [175] studied the effect of sonoporation and softshell/hardshell microbubbles on tumour
accumulation of fluorophore-labelled 100 nm liposomes in mice bearing A431, BxPC-3 tumour. There was
a 100% enhancement in tumour accumulation of liposome.

In another study, Yan et al. [176] attached paclitaxel encapsulated liposomes to the lipid shell of microbubbles
via avidin-biotin linkage. They achieved high encapsulation efficiency of doxorubicin and upon
application of ultrasonic sound of optimized intensity for the optimal period of time, there was significant
enhancement in the uptake of drug molecules in 4T1 breast tumours by EPR.

As an alternative approach, Meng et al. [177] developed a doxorubicin loaded nanobubble [Figure 5]. It
consisted of a core of a polymeric network where doxorubicin is dispersed. This core was encapsulated
in a perfluoropropane gas bubble, the lipid shell of which was further stabilized with pluronic molecules.
When delivered intravenously in combination with therapeutic ultrasonication, this ~170 nm diameter
nanobubble showed higher accumulation and better distribution of doxorubicin in tumours, leading to
significantly higher intracellular uptake and therapeutic efficacy.

Hyperthermia
In response to temperatures of 41-45 °C, there is increased tissue perfusion to dissipate heat. For healthy
tissues like muscle and skin, this increase in perfusion can be as high as 10- and 15-fold respectively.