Microbubble-Mediated Enhanced Delivery of Curcumin to Cervical Cancer Cells.

Awaneesh Upadhyay,Bhrugu Yagnik,Sameer V Dalvi,Priti Desai

doi:10.1021/acsomega.8b01737

Abstract

The major bottleneck in the current chemotherapy treatment of cancer is the low bioavailability and high cytotoxicity. Targeted delivery of drug to the cancer cells can reduce the cytotoxicity and increase the bioavailability. In this context, microbubbles are currently being explored as drug-delivery vehicles to effectively deliver drug to the tumors or cancerous cells. Microbubbles when used along with ultrasound can enhance drug uptake and inhibit the growth of tumor cells. Several potential anticancer molecules exhibit poor water solubility, which limits their use in therapeutic applications. Such poorly water soluble molecules can be coadministered with microbubbles or encapsulated within or loaded on the microbubbles surface, to enhance the effectiveness of these molecules against cancer cells. Curcumin is one of such potential anticancer molecules obtained from the rhizome of herbal spice, turmeric. In this work, curcumin-loaded protein microbubbles were synthesized and examined for effective in vitro delivery of curcumin to HeLa cells. Microbubbles in the size range of 1–10 μm were produced using perfluorobutane as core gas and bovine serum albumin (BSA) as shell material and were loaded with curcumin. The amount of curcumin loaded on the microbubble surface was estimated using UV–vis spectroscopy, and the average curcumin loading was found to be ∼54 μM/108 microbubbles. Kinetics of in vitro curcumin release from microbubble surface was also estimated, where a 4-fold increase in the rate of curcumin release was obtained in the presence of ultrasound. Sonication and incubation of HeLa cells with curcumin-loaded BSA microbubbles enhanced the uptake of curcumin by ∼250 times. Further, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed ∼71% decrease in cell viability when HeLa cells were sonicated with curcumin-loaded microbubbles and incubated for 48 h.

Highlights

Researchers are exploring targeted and efficient delivery of anticancer drug molecules to tumor cells to minimize the damage caused to healthy cells.[1]
The curcumin−bovine serum albumin (BSA) conjugation was confirmed through fluorescence and UV−vis studies
The curcumin uptake was enhanced by ∼250 times when HeLa cells were subjected to ultrasound in the presence of curcumin-loaded microbubbles compared to HeLa cells sonicated only with curcumin solution

Summary

Introduction

Researchers are exploring targeted and efficient delivery of anticancer drug molecules to tumor cells to minimize the damage caused to healthy cells.[1]. A naturally occurring molecule, derived from the rhizome of an herbal spice, turmeric, is known to possess anticancer properties.[22−25] curcumin suffers from poor aqueous solubility and low bioavailability.[22] an efficient way of curcumin delivery (such as loading the drug cargo directly on drug-delivery vehicles) needs to be adopted (rather than traditional drug-delivery routes) to enhance its effectiveness against cancer cells. Curcumin uptake by HeLa cells was found to increase, and the cell viability was found to reduce significantly when curcuminloaded BSA microbubbles (CuB MBs) were used along with ultrasound. This is the first report where microbubbles with

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Results

Conclusion