Ultrasound responsive proapoptotic drug delivery platform for image-guided therapeutics
Rajeet Chandan and Rinti Banerjee
Indian Institute of Technology, India
: J Pharm Drug Deliv Res
Abstract
Recently, liposomes-microbubble conjugates have emerged as a promising ultrasound (US)-responsive platform for cancer therapeutics. However, these are limited by their size in terms of tumor penetration. Additionally, there have been no attempts to enhance the smartness of the liposomes-bubble conjugates which have been used only as passive carriers. The present study explores submicron sized (756±180.0 nm), US-responsive, PhosphatidylSerine (PS)- based Paclitaxel-Liposomes-nanoBubble Conjugates (PSPLBC) with an additional pro-apoptotic effect towards enhanced anti-cancer efficacy and image-guidance. The developed PSPLBC underwent cavitation in response to US trigger, exhibiting in vitro pulsatile release with a 10-fold increase in cellular internalization as compared to control. The PS-containing formulations were found to be proapoptotic and exhibited strong synergism between PS and paclitaxel (Combination Index, CI < 0.1). This resulted in significantly high anti-tumor efficacy both in vitro and in vivo conditions (98.3±0.8% tumor growth inhibition, TGI) and 100% survival rate as compared to placebo control. Significant reduction in tumor proliferation index and microvessel density (MVD), as well as significant increase in apoptosis, were observed for the treated tumor sections. Further, the intravenous (IV) administration of PSPLBC enhanced the tumor US-contrast by 2-fold as compared to SonoVue®, a commercial ultrasound contrast agent (UCA), suggesting the image-guided therapeutic potential of the developed pro-apoptotic liposomenanobubble conjugates. These results show the potential of the developed liposomenanobubble conjugate as a sub-micron-sized, smart pro-apoptotic platform for US-image-guided and triggered delivery of a variety of drugs in case of various biomedical applications such as cancer.
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