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Delivery Vectors (delivery + vector)
Kinds of Delivery Vectors Selected AbstractsSurface-Functionalized Ultrasmall Superparamagnetic Nanoparticles as Magnetic Delivery Vectors for CamptothecinCHEMMEDCHEM, Issue 6 2009Feride Cengelli Abstract Drug,nanoparticle conjugates: The anticancer drug camptothecin (CPT) was covalently linked at the surface of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) via a linker, allowing drug release by cellular esterases. Nanoparticles were hierarchically built to achieve magnetically-enhanced drug delivery to human cancer cells and antiproliferative activity. The linking of therapeutic drugs to ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) allowing intracellular release of the active drug via cell-specific mechanisms would achieve tumor-selective magnetically-enhanced drug delivery. To validate this concept, we covalently attached the anticancer drug camptothecin (CPT) to biocompatible USPIOs (iron oxide core, 9,10,nm; hydrodynamic diameter, 52,nm) coated with polyvinylalcohol/polyvinylamine (PVA/aminoPVA). A bifunctional, end-differentiated dicarboxylic acid linker allowed the attachment of CPT to the aminoPVA as a biologically labile ester substrate for cellular esterases at one end, and as an amide at the other end. These CPT,USPIO conjugates exhibited antiproliferative activity in,vitro against human melanoma cells. The intracellular localization of CPT,USPIOs was confirmed by transmission electron microscopy (iron oxide core), suggesting localization in lipid vesicles, and by fluorescence microscopy (CPT). An external static magnetic field applied during exposure increased melanoma cell uptake of the CPT,USPIOs. [source] Preparation of monomethyl poly(ethylene glycol)- g -chitosan copolymers with various degrees of substitution: Their ability to encapsulate and condense plasmid DNAJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2008Wei Zhang Abstract Chitosan (CS) has great potential as a nonvirus gene delivery vector, but its application is limited because of poor water solubility. Monomethyl poly(ethylene glycol) (mPEG)- graft -CS copolymers were synthesized by the reaction of mPEG,aldehyde (oxidized mPEG) with amino groups on CS chains; they showed enhanced solubility in water. Copolymers with various mPEG degrees of substitution (DS) and CS molecular weights were obtained, and their capabilities of DNA encapsulation were compared through gel retardation assay and particle size and , potential measurements. The effects of different ratios of primary amines on CS to the phosphate groups on DNA (N/P ratios), DS, and molecular weights on particle size and encapsulation efficiency were investigated. The results show that high N/P ratios and proper DS were necessary for the formation of well-distributed complex particles. Among all of these samples, mPEG (3.55),CS (50 kDa)/DNA complexes [where the parentheses following mPEG indicate DS (%), and the parentheses following CS indicate the molecular weight of CS] raised the , potential from negative to positive most quickly, yielded the smallest particle size, and were retarded in agarose gel at the lowest N/P ratio; this indicated the best efficiency of DNA encapsulation. On the contrary, mPEG (0.80),CS (50 kDa)/DNA complexes raised the , potential to positive most slowly, fluctuated around the value 0 from N/P ratios of 15 : 1 to 30 : 1, and were retarded in agarose gel at the highest N/P ratio; this indicated the lowest efficiency of encapsulating plasmids. Copolymers with desirable efficiencies of DNA encapsulation could be promising gene carriers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Lack of dendritic cell maturation by the plant toxin ricinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2004Daniel Abstract Several bacterial toxins either promote or inhibit the maturation of human monocyte-derived DC. Since the potent plant toxin ricin exploits the same cell entry pathway used by these bacterial toxins and shares identical catalytic activity with some of them, we have studied the capacity of ricin to induce DC maturation in vitro. Here, we show that in contrast to the bacterial proteins, ricin neither induces DC maturation nor interferes with LPS-induced DC maturation. There is no correlation between the absence of DC maturation and ricin dysfunction. Indeed, some of the ricin variants retain significant ribotoxicity and catalytic activity. We have extended these observations to ebulin-1, suggesting that this may be a general characteristic of plant-derived cytotoxic ribosome-inactivating toxins. The human immune system may therefore have evolved to recognize and rapidly respond to the bacterial proteins, whilst being less responsive to the equivalent plant cytotoxins. Understanding the effect of ricin on professional APC may provide insights into the generation of an anti-ricin vaccine and into the use of inactivated ricin A,chains as delivery vectors as part of a vaccination protocol. [source] Brush-Like Amphoteric Poly[isobutylene- alt -(maleic acid)- graft -oligoethyleneamine)]/DNA Complexes for Efficient Gene TransfectionMACROMOLECULAR RAPID COMMUNICATIONS, Issue 13 2010Majad Khan Abstract Synthetic gene delivery vectors, especially cationic polymers have attracted enormous attention in recent decades because of their ease of manufacture, targettability, and scaling up. However, certain issues such as high cytotoxicity and low transfection efficiency problems have hampered the advance of nonviral gene delivery. In this study, we designed and synthesized brush-like amphoteric poly[isobutylene- alt -(maleic acid)- graft -oligoethyleneamine] capable of mediating highly efficient gene transfection. The polymers are composed of multiple pendant oligoethyleneimine molecules with alternating carboxylic acid moiety grafted onto poly[isobutylene- alt -(maleic anhydride)]. The polymer formed from pentaethylenehexamine {i.e., poly[isobutylene- alt -(maleic acid)- graft -pentaethylenehexamine)]} was able to condense DNA efficiently into nanoparticles of size around 200,nm with positive zeta potential of about 28,30,mV despite its amphoteric nature. Luciferase expression level and percentage of GFP expressing cells induced by this polymer was higher than those mediated with polyethyleneimine (branched, 25,kDa) by at least one order of magnitude at their optimal N/P ratios on HEK293, HepG2, and 4T1 cells. In vitro cytotoxicity testing revealed that the polymer/DNA complexes were less cytotoxic than those of PEI, and the viability of the cells after being incubated with the polymer/DNA complexes at the optimal N/P ratios was higher than 85%. This polymer can be a promising gene delivery carrier for gene therapy. [source] Modification of pLL/DNA complexes with a multivalent hydrophilic polymer permits folate-mediated targeting in vitro and prolonged plasma circulation in vivoTHE JOURNAL OF GENE MEDICINE, Issue 5 2002Christopher M. Ward Abstract Background Gene delivery vectors based on poly(L -lysine) and DNA (pLL/DNA complexes) have limited use for targeted systemic application in vivo since they bind cells and proteins non-specifically. In this study we have attempted to form folate-targeted vectors with extended systemic circulation by surface modification of pLL/DNA complexes with hydrophilic polymers. Methods pLL/DNA complexes were stabilised by surface modification with a multivalent reactive polymer based on alternating segments of poly(ethylene glycol) and tripeptides bearing reactive ester groups. Folate moieties were incorporated into the vectors either by direct attachment of folate to the polymer or via intermediate poly(ethylene glycol) spacers of 800 and 3400,Da. Results Polymer-coated complexes show similar morphology to uncoated complexes, their zeta potential is decreased towards zero, serum protein binding is inhibited and aqueous solubility is substantially increased. Intravenous (i.v.) administration to mice of coated complexes produced extended systemic circulation, with up to 2000-fold more DNA measured in the bloodstream after 30,min compared with simple pLL/DNA complexes. In further contrast to simple pLL/DNA complexes, coated complexes do not bind blood cells in vivo. Folate receptor targeting is shown to mediate targeted association with HeLa cells in vitro, leading to increased transgene expression. We demonstrate for the first time that DNA uptake via the folate receptor is dependent on pEG spacer length, with the transgene expression relatively independent of the level of internalised DNA. Conclusions We show increased systemic circulation, decreased blood cell and protein binding, and folate-targeted transgene expression using pLL/DNA complexes surface-modified with a novel multireactive hydrophilic polymer. This work provides the basis for the development of plasma-circulating targeted vectors for in vivo applications. Copyright © 2002 John Wiley & Sons, Ltd. [source] Influence of N-Terminal Hydrophobicity of Cationic Peptides on Thermodynamics of their Interaction with Plasmid DNACHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2009Geetha N. Goparaju There is a need to understand the thermodynamics of interaction of cationic peptides with DNA to design better peptide based non-viral gene delivery vectors. The main aim of this study was to understand the influence of N-terminal hydrophobicity of cationic amphiphilic peptides on thermodynamics of interaction with plasmid DNA. The model peptides used were TATPTD and TATPTDs modified at the N-terminal with hydrophobic amino acids. The thermodynamic binding data from isothermal titration calorimetry were compared with ethidium bromide analysis and ultrafiltration to correlate the binding parameters with the structural features of the various peptides used. It was observed that peptides having a smaller hydrophobic domain at the N-terminal have good DNA condensing ability compared with the ones with a longer hydrophobic domain. Calorimetry of peptides that reached saturation binding indicated that enthalpy and entropy are favorable for the interaction. Moreover, the interaction of these peptides with DNA appears to be predominantly electrostatic. [source] | |||||||||||||