The present study evaluates the efficacy of drug polymer self folding nano-conjugates of pectin-cisplatin to enhance blood circulating levels of cisplatin. The binding of nano-conjugate was confirmed by a peak-shift in UV-spectra. Physical characterization was done by DLS and TEM. Pharmacokinetics and bio-distribution of the nano-conjugates were performed at various time points in normal, Balb-c mice. Zeta Potential showed the shielding effect on the negative potential of pectin that was ∼7 times more than the pectin chains when conjugated with cisplatin. TEM confirmed the formation of a hydrophilic, easily re-dispersible nano-conjugate in the size range of 100nm. Release kinetics in plasma showed that the pectin-cisplatin conjugate is a stable, slow and sustained system with no burst effect. Immunofluorescence analysis of J-774, a mouse macrophage cell line, was assessed after incubating the cells with pectin chains tagged with FITC as well as Pectin-Cisplatin-FITC conjugates. With the cellular uptake of these particles in J-774, 40% of the cells showed an uptake post 30 min of incubation. However, Pectin chains were clearly eliminated. The plasma proteins facilitate the release of cisplatin with 85-89% of the drug being released in 17 days, and only 57% of drug was released in ∼ 30 days without plasma. The reduced negative charge on the conjugate helps in adhesion to the cell surface and subsequent uptake by cells as evidenced by cell uptake studies on J-774 cell line. Nano-conjugates showed long blood retention profile in mice and the cisplatin was found in circulation even after 24 hrs. Pharmacokinetic study clearly indicates that it can form a novel anticancer drug that possesses good efficacy and has a safer profile than cisplatin.
Keywords: Pectin- cisplatin, nano-conjugates, zeta potential, bio-distribution, cell uptake, pharmacokinetics
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