Decapeptide Modified Doxorubicin Loaded Solid Lipid Nanoparticles as Targeted Drug Delivery System against Prostate Cancer.

Abstract

Growing instances of prostate cancer with poor prognosis have become a challenging task in cancer therapy. Luteinizing-hormone-releasing-hormone (LHRH) receptors are overexpressed in prostate cancer cells. Polyethylene glycol (PEG) conjugated lipids exhibit superiority in terms of retention/circulation in biological systems. PEGylated dipalmitoylphosphatedylethanolamine (DPPE-PEG), covalently linked with 6-hydrazinopyridine-3-carboxylic-acid, was conjugated with new LHRH-receptor positive peptide analog (DPPE-PEG-HYNIC-d-Glu-His-Trp-Ser-Tyr-d-Asn-Leu-d-Gln-Pro-Gly-NH2). Surface modified doxorubicin (DOX) loaded solid lipid nanoparticle (SLN) was prepared using soylecithin, stearic acid and Poloxamer-188 by solvent emulsification/evaporation method for targeted delivery of DOX into prostate cancer cells. SLN, DOX loaded SLN (DSLN) and surface modified DSLN (M-DSLN) were characterized by means of their size, zeta potential, morphology, storage time, drug payload, and subsequent release kinetics studies. Homogeneity of surface morphology, upon modification of SLN, was revealed from the dynamic light scattering, atomic force microscopy, and scanning electron microscopic studies. Homogeneous adsolubilization of DOX throughout the hydrophobic moiety of SLN was established by the differential scanning calorimetric studies. Release of DOX were sustained in DSLN and M-DSLN. Cellular uptake and in vitro activities of formulations against LHRH positive PC3/SKBR3 cancer cell lines revealed higher cellular internalization, cytotoxicity that followed the sequence DOX < DSLN < M-DSLN. Dye staining and flow cytometry studies revealed higher apoptosis in cancer cells. Such receptor specific drug delivery systems are considered to have substantial potential in prostate cancer therapy.