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Hindi Hollow calcium carbonate nanoparticles as pH-sensitive targeted delivery carriers in cancer therapy
Anjala W Bulathge, M M M G P G Mantilaka and R M G Rajapakse
University of Peradeniya, Sri Lanka
: J Pharm Drug Deliv Res
Abstract
pH sensitive drug delivery systems can achieve targeted drug delivery and systemic control release. The studies in this area have been increased in recent years and more attention has been devoted to develop new methods for the preparation of new drug delivery systems especially in cancer therapy. Among the metal based anti-cancer drugs, copper complexes have shown remarkable potential in cancer therapy. Therefore, the aim of this study is to synthesize a pH-sensitive calcium carbonate-encapsulated copper bis-(8-hydroxyquinoline) anti-cancer drug delivery system starting from naturally occurring dolomite. In this novel research, first, copper bis-(8-hydroxyquinoline) is synthesized using copper(II) chloride dihydrate and 8-hydroxyquinoline as the reactants. The drug was loaded to the preformed hollow structures of precipitated calcium carbonate (PCC) by physisorption method. Hollow structures of PCC were suspended in prepared solution of Copper bis-(8-hydroxyquinoline) dissolved in Dimethylformamide (DMF). It was moderately stirred for five days. PCC products were collected by centrifugation followed by washing with acetone to remove the DMF. The obtained product was characterized using XRD, XRF and FTIR studies. XRD and FTIR studies revealed that copper bis-(8-hydroxyqunoline) incorporated inside the CaCO3 hollow PCC product. The release of drug is monitored in vitro in the pH values of 2.0, 4.0, 6.0 and 8.0. According to results, within first four hours, the cumulative release shows 100% in pH 2 and pH 4. However, no release is observed in pH 8 for 120 hours. Therefore, it is a good indication that the encapsulated drug releases at the pH trigger point. pH differences can be found at the subcellular level, late endosomes and lysosomes have much lower pH, in the range 4.5–5.5 . Due to high rate of glycolysis, tumors exhibit pH value 5.7 while the pH value of normal tissue is 7.4. This pH gradient is very important in internalization of drugs. Therefore this has potential applications in effective cancer therapy.
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