Synthesis of Unstable Vaterite Polymorph of Porous Calcium Carbonate Nanoparticles, Encapsulation of Anticancer Drug Cisplatin, Studying Release Kinetics for Safe, Targeted Delivery and Slow Release

Abstract

Cisplatin is a commonly used anticancer drug which is the first generation of platinum-based anticancer drugs developed. The cis configuration enables the binding of the coordination complex to one or two DNA strand (s) and thereby crosslinking the DNA strands triggering the cells to die in a programmed manner. It is used to treat various types of cancers such as small cell lung cancer, ovarian cancer, bladder cancer, cervical cancer, and germ cell tumours. When administered into blood, cisplatin reacts with thiol containing proteins present in blood plasma thus reducing its bioavailability, increasing cytotoxicity and it is associated with numerous side effects including nephrotoxicity, neurotoxicity, nausea, vomiting and ototoxicity. In order to increase the bioavailability and to reduce dosage and cytotoxic effects to healthy cells thermodynamically unstable vaterite form of Porous Calcium Carbonate Nanoparticles are synthesized using the soft molecular template approach to synthesize them from aqueous solution. Hydrogen bonded networks of ethylene glycol and water are formed by mixing appropriate quantities of the two liquids to have spherical templates. Cisplatin is encapsulated in porous nanoparticles of the vaterite form of CaCO3 and studied the release kinetics of the drug in the solutions at different pH values. It is found that the drug is released slowly and steadily in the pH values of cancerous cells (pH range 5.0–6.0) but not in the pH ranges exhibited by healthy cells (pH range 7.0-8.0). Here, the synthesis and stabilization of nanoparticles of vaterite as well as their characterization, encapsulation of cisplatin and the slow minimum amount of constant release kinetics of the drug at various pH values are described. This is a way forward for safe and convenient chemotherapeutic route to various cancers. Graphical Abstract