HER2 targeted biological macromolecule modified liposomes for improved efficacy of capecitabine in breast cancer.

The present research reports the beneficial effects of surface modified chitosan and tumor-homing peptide conjugated liposomes of capecitabine (CAP) for treating breast cancer. Liposomal formulation of CAP was prepared by film hydration method using cholesterol-THP conjugate (CTHP-CAP-LPs) to achieve active targeting through HER2 receptors. CTHP-CAP-LPs significantly improved the specificity and efficacy of CAP by improving cell uptake, cytotoxicity and tumor regression in tumor bearing mice. CTHP-CAP-LPs, therefore, is a promising approach to improve the anticancer effects of CAP.

Tumor homing peptide modified liposomes of capecitabine for improved apoptotic activity and HER2 targeted therapy in breast cancer: in vitro studies.

In the present study, we have formulated a liposomal formulation of cytotoxic agent capecitabine (CAP) to overcome its bioavailability issues. Then we have surface modified CAP loaded liposomes (CAP-LPs) with a tumour homing peptide (THP-CAP-LPs) to achieve site specific delivery to breast cancer cells. We found a significant cellular internalization of THP-CAP-LPs when compared to unmodified CAP-LPs. The cytotoxic effect of CAP was also significantly improved with THP-CAP-LPs by downregulating anti-apoptotic proteins and upregulating pro-apoptotic proteins as observed by Western blot analysis. THP-CAP-LPs mediated delivery of CAP can be, therefore, a promising approach for improving antitumor activity and reducing off-target effects.

Design and development of hydrogel nanoparticles for mercaptopurine.

Hydrogel nanoparticles have gained attention in recent years as they demonstrate the features and characters of hydrogels and nanoparticles at the same time. In the present study chitosan and carrageenan have been used, as hydrogel nanoparticles of mercaptopurine are developed using natural, biodegradable, and biocompatible polymers like chitosan and carrageenan. As these polymers are hydrophilic in nature, the particles will have a long life span in systemic circulation. Hydrogel nanoparticles with mercaptopurine is form an antileukemia drug by the counter polymer gelation method. Fourier-Transform Infrared (FT-IR) studies have shown a compatibility of polymers with the drug. The diameter of hydrogel nanoparticles was about 370 - 800 nm with a positive zeta potential of 26 - 30 mV. The hydrogel nanoparticles were almost spherical in shape, as revealed by scanning electron microscopy (SEM). Drug loading varied from 9 to 17%. Mercaptopurine released from the nanoparticles at the end of the twenty-fourth hour was about 69.48 - 76.52% at pH 7.4. The drug release from the formulation was following zero order kinetics, which was evident from the release kinetic studies and the mechanism of drug release was anomalous diffusion, which indicated that the drug release was controlled by more than one process.