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.

Synthesis, Characterization, and Biological Evaluation of Radiolabeled Glutamine Conjugated Polymeric Nanoparticles: A Simple Approach for Tumor Imaging

“…The stability of the solution is shown by the zeta potential, which is dependent on the polymer’s composition. Values near zero show little NP-NP repulsion, which can result in the development of colloids. , The zeta potential of PLGA-NPs is decreased by using PVA 2% in aqueous phase during the production process. The zeta potential also becomes less negative as PVA content in solution rises, which may cause sample instability and NP aggregation to become more pronounced with time .…”

“…The surface properties of the nanoparticles were determined by atomic force microscopy (AFM) following the procedure described by a previous report. , Lyophilized glutamine-conjugated PNP was collected, and surface conjugation was established by Fourier-transform infrared (FTIR) analyses and X-ray photoelectron spectroscopy (XPS) analysis. , …”

“…For assessing the long-term stability, nanoformulations were stored at 4 °C for three months and analyzed for size distribution, polydispersity index (PDI), and zeta potential value as per methods described earlier. , …”

“…44,45 Lyophilized glutamine-conjugated PNP was collected, and surface conjugation was established by Fourier-transform infrared (FTIR) analyses and X-ray photoelectron spectroscopy (XPS) analysis. 44,45 2.5. Long-Term Stability Study.…”

In Vitro Evaluation of Nanoerythrosome Cytotoxicity and Uptake in Pancreatic Endothelial Cells: Implications for β-Cell Imaging Applications

“…Several NPs have been studied and designed for cell tracking and theranostic purposes. − Hard and soft matter-based carriers such as silica NPs, − lamellar, − and nonlamellar − lipid liquid crystalline nanoparticles have been shown to be good candidates in nanomedicine for in vitro and in vivo applications. Although significant progress has been made so far, practical limitations such as insufficient biocompatibility and short in vivo half-life have hindered their application in nanomedicine .…”