curcumin and pyrene

Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.. A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI. Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 µg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.. These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Curcumin; Drug Delivery Systems; Gene Transfer Techniques; Lipopeptides; Mice; Plasmids; Polyethyleneimine; Pyrenes; Transfection; Urinary Bladder Neoplasms

Casein-dextran nanoparticles (CDNs) were prepared from casein-dextran conjugates by heating in a dry/wet state and then adjusting the pH to the isoelectric point of the protein (pH 4.6) to investigate their physicochemical characteristics. The effects of the dry and wet heating methods on the properties of the CDNs were also evaluated. The CDNs were spherically shaped and uniformly dispersed, as confirmed by atomic force microscopy. Compared with CDNs prepared by wet heating (CDN-W), those prepared by dry heating (CDN-D) were much smaller (P<0.05) and showed superior stability and enhanced the release of curcumin under simulated gastrointestinal conditions. However, both types exhibited the same encapsulation ability of curcumin. Meanwhile, the CDNs displayed good thermal, gastrointestinal and storage stability, and good redispersion behaviour. Our findings indicated CDN-D exhibited superior physicochemical properties and could serve as a potential delivery vehicle to encapsulate hydrophobic active ingredients to intestine.

Topics: Calorimetry, Differential Scanning; Caseins; Curcumin; Dextrans; Drug Liberation; Fluorescence; Gastrointestinal Tract; Heating; Humidity; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Micelles; Microscopy, Atomic Force; Nanoparticles; Particle Size; Pyrenes

The cell membrane is an ordered environment, which anisotropically affects the structure and interactions of all of its molecules. Monitoring membrane orientation at a local level is rather challenging but could reward crucial information on protein conformation and interactions in the lipid bilayer. We monitored local lipid ordering changes upon varying the cholesterol concentration using polarized light spectroscopy and pyrene as a membrane probe. Pyrene, with a shape intermediate between a disc and a rod, can detect microscopic orientation variations at the level of its size. The global membrane orientation was determined using curcumin, a probe with nonoverlapping absorption relative to that of pyrene. While the macroscopic orientation of a liquid-phase bilayer decreases with increasing cholesterol concentration, the local orientation is improved. Pyrene is found to be sensitive to the local effects induced by cholesterol and temperature on the bilayer. Disentangling local and global orientation effects in membranes could provide new insights into functionally significant interactions of membrane proteins.

Topics: Cholesterol; Curcumin; Light; Lipid Bilayers; Liposomes; Molecular Probes; Phosphatidylcholines; Pyrenes; Spectrum Analysis

The inherent instability of micelles remains a main challenge for antitumor drug delivery, the objective of this study is to prepare and characterize the ion-fixed mixed micelles with significantly improved stability. The mixed micelles and ion-fixed mixed micelles combining the carboxy-containing PLA (PLA-COO(-)) and mPEG-PLA were formed by inserting PLA-COO(-) into micellar core without and with metal ions, respectively. The critical micelle concentration (CMC) of mixed micelle depended on the origin PLA length in the mPEG-PLA, whereas kinetic stability of the mixed micelles was significantly improved, irrespective of the PLA length. However, curcumin (Cur)-loaded mixed micelles did not show higher physical stability upon dilution and Cur-micelle bonding constant due to the lower loading space. On the contrary, the ion-fixed mixed micelles formed in the presence of CaCl2 solution showed a high physical stability upon dilution due to the solidification of micellar core by forming the more hydrophobic (PLA-COO(-))2 Ca(2+) complex. The Cur-loaded ion-fixed mixed micelles showed the comparable cellular uptake of Cur and cytotoxicity in comparison with mPEG-PLA micelles. Our study highlights a universal combining strategy of ion-fixed mixed micelles with superior stability to individual micelles for antitumor drug delivery.

Topics: Antineoplastic Agents; Cell Survival; Curcumin; Drug Compounding; HeLa Cells; Humans; Lactic Acid; Micelles; Nanoparticles; Polyesters; Polyethylene Glycols; Polymers; Pyrenes