Poly(ethylene carbonate) nanoparticles as carrier system for chemotherapy showing prolonged in vivo circulation and anti-tumor efficacy.
ABSTRACT The aim of this study is to investigate the feasibility and efficacy of PEC nanoparticles as delivery system for cancer chemotherapy. Assembly of paclitaxel-loaded nanoparticles with high loading efficiency and narrow-size distribution is successful. For non-invasive in vivo tracing, nanoparticle blends of chelator bearing poly(lactide) with PEC and PLGA are successfully prepared. Pharmacokinetic studies in mice reveal a twofold higher circulation time of PEC as compared to PLGA. A tumor model shows an accumulation of PEC NPs in cancerous tissue and a higher anti-tumor efficiency compared to the standard Taxol™, which is reflected in a significantly slower tumor growth compared to the NaCl control group.
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ABSTRACT: Poloxamer 188 is a complex polydisperse mixture of non-ionic macromolecules. Adverse non-IgE-mediated hypersensitivity reactions occur in some individuals following intravenous injection of poloxamer 188-based pharmaceuticals, presumably via complement activation. Here we have delineated potential causal chemical and biological interactive factors behind poloxamer 188-induced complement activation in human serum specimens. We identified the molecular constituents inherent in poloxamer 188 preparations and studied their effect on generation of the two complement split products, SC5b-9 and Bb. Poloxamer 188 activated complement at sub-micellar concentrations and the results indicated the potential involvement of all three known complement activation pathways. The poloxamer-induced rise of SC5b-9 in human sera was abolished in the presence of a recombinant truncated soluble form of complement receptor type 1, thus confirming the role of C3/C5 convertases in the activation process. Poloxamer 188-mediated complement activation is an intrinsic property of these macromolecules and was independent of the degree of sample polydispersity, as opposed to other non-polymeric constituents. Poloxamer 188 preparations also contained unsaturated chains of diblock copolymers capable of generating SC5b-9 in human sera; this effect was terminated following the removal of double bonds by catalytic hydrogenation. By quasi-elastic light scattering, we established interaction between poloxamer and lipoproteins; interestingly, poloxamer-induced rise in SC5b-9 was significantly suppressed when serum HDL and LDL cholesterol levels were increased above normal to mimic two relevant clinical situations. This observation was consistent with previously reported data from patients with abnormal or elevated lipid profiles where no or poor complement activation by poloxamer 188 occurred. Our findings could provide the basis of novel approaches to the prevention of poloxamer-mediated complement activation.Biochimica et Biophysica Acta 07/2004; 1689(2):103-13. · 4.66 Impact Factor
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ABSTRACT: Poly(L-lactide) (PLA) microspheres tailored with a tridentate chelating group were radiolabeled with [(99m)Tc(H(2)O)(3)(CO)(3)](+) and optimized for labeling efficiency and stability. Various ligand-polymer blend compositions with commercial PLA (from 2% to 100%) were evaluated. Labeling efficiencies over 95% were achieved in a 5 min reaction using 100% of the ligand-polymer or within 15 min using a 5% ligand-polymer blend. The addition of 1.5% of PEGylated copolymer to the blend did not affect the labeling efficiency of these particles but changed their in vivo behavior. MicroSPECT/CT imaging showed significant uptake of non-PEGylated microspheres by the murine lung, while only the liver and spleen took up PEGylated microspheres. Such (99m)Tc radiolabeled biodegradable microspheres will be useful diagnostic imaging agents for visualization of the functioning reticuloendothelial system (RES). Similarly, other sizes of the same microspheres will allow imaging of lung perfusion, bone marrow, lymph and inflammation scintigraphy, and radioembolization therapy.Bioconjugate Chemistry 07/2009; 20(6):1209-17. · 4.58 Impact Factor
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ABSTRACT: Over the last few decades, colloidal drug delivery systems (CDDS) such as nano-structures have been developed in order to improve the efficiency and the specificity of drug action. Their small size permits them to be injected intravenously in order to reach target tissues. However, it is known that they can be rapidly removed from blood circulation by the immune system. CDDS are removed via the complement system and via the cells of the mononuclear phagocyte system (MPS), after their recognition by opsonins and/or receptors present at the cell surface. This recognition is dependent on the physicochemical characteristics of the CDDS. In this study, we will focus on parameters influencing the interactions of opsonins and the macrophage plasma membrane with the surface of CDDS, whereby parameters of the polymer coating become necessary to provide good protection.Biomaterials 09/2006; 27(24):4356-73. · 7.60 Impact Factor