Poly(ethylene carbonate) nanoparticles as carrier system for chemotherapy showing prolonged in vivo circulation and anti-tumor efficacy.

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.

Drug eluting stents based on Poly(ethylene carbonate): optimization of the stent coating process.

First generation drug eluting stents (DES) show a fivefold higher risk of late stent thrombosis compared to bare metal stents. Therefore, new biodegradable and biocompatible polymers for stent coating are needed to reduce late stent thrombosis. In this study, a reproducible spray-coating process for stents coated with Poly(ethylene carbonate), PEC, and Paclitaxel was investigated.

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide.

Background: Sandostatin® LAR® (Novartis Pharma AG) is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid) technology have been developed. This study compares the composition and pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries).

Biodegradable poly(ethylene carbonate) nanoparticles as a promising drug delivery system with "stealth" potential.

The goal of this study was to investigate the suitability of poly(ethylene carbonate) (PEC) nanoparticles as a novel drug delivery system, fulfilling the requirements for a long circulation time. Particles were obtained with a narrow size distribution and nearly neutral zeta potential. Adsorption studies with human plasma proteins revealed that PEC nanoparticles bind much less proteins in comparison to polystyrene (PS) nanoparticles.

A two-stage strategy for sterilization of poly(lactide-co-glycolide) particles by γ-irradiation does not impair their potency for vaccine delivery.

This study evaluated the feasibility of using γ-irradiation for preparing sterile poly(lactide-co-glycolide) (PLG) formulations for vaccines. PLG microparticles were prepared by water-in-oil-in-water double-emulsion technique and lyophilized. The vials were γ-irradiated for sterilization process.

Biocompatibility of an injectable in situ forming depot for peptide delivery.

Poly(ethyleneglycol) 500 dimethylether (PEG500DME) was tested as a novel solvent for the manufacture of an injectable in situ forming depot (ISFD) containing poly(D,L-lactide-co-glycolide) (PLGA). The sustained release of pasireotide from the ISFD was evaluated in vitro and in vivo. Furthermore, the local tolerability of the delivery system using PEG500DME was investigated in subcutaneous (s.

Poly(ethylene carbonate) as a surface-eroding biomaterial for in situ forming parenteral drug delivery systems: a feasibility study.

To evaluate the technical feasibility of poly(ethylene carbonate), PEC, for injectable in situ forming drug delivery systems, the physical properties of PEC solutions were characterized. The solubility of PEC was investigated in different solvents, and the Hildebrand solubility parameters and Flory-Huggins interaction parameters of PEC were determined. By turbidity titration, the experimental ternary phase diagram of water-NMP/DMSO-PEC was constructed.

Poly(ethyleneglycol) 500 dimethylether as novel solvent for injectable in situ forming depots.

Purpose: Poly(D,L-lactide-co-glycolide) (PLGA) solutions in poly(ethyleneglycol)600 (PEG600), N-methyl-2-pyrrolidone (NMP) and poly(ethyleneglycol)500 dimethylether (PEG500DME) as a novel solvent, were investigated as suitable for use in injectable in situ forming depots (ISFD).

Methods: The hemolytic potential of the solvents was investigated. Viscosimetry was used to determine rheological properties of solvents and PLGA solutions.

PEGylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice.

The influence of PEGylation on polyplex stability from poly(ethylene imine), PEI, and plasmid DNA was investigated both in vitro and after intravenous administration in mice. Polyplexes were characterized with respect to particle size (dynamic light scattering), zeta-potential (laser Doppler anemometry), and morphology (atomic force microscopy). Pharmacokinetics and organ accumulation of both polymers and pDNA were investigated using 125I and 32P radioactive labels, respectively.

Effect of poly(ethylene imine) molecular weight and pegylation on organ distribution and pharmacokinetics of polyplexes with oligodeoxynucleotides in mice.

The in vivo body distribution and the pharmacokinetics of a 20mer double-stranded nuclear factor kappaB decoy oligodeoxynucleotide (ODN) complexed with 25-kDa poly(ethylene imine) (PEI), low molecular weight 2.7-kDa PEI, and PEGylated PEI [bPEI(25k)-glPEG(550)(50)] after intravenous injection were studied in BALB/c mice using a double-labeling technique to follow simultaneously the distribution of both complex components. The polymers were radioactively labeled with (125)I by Bolton-Hunter reagent and the decoys with [gamma-(32)P]ATP by an enzymatic 5'-end-labeling technique.

Physicochemical and biological characterization of polyethylenimine-graft-poly(ethylene glycol) block copolymers as a delivery system for oligonucleotides and ribozymes.

Two different series of polyethylenimine (PEI) block copolymers grafted with linear poly(ethylene glycol) (PEG) were investigated as delivery systems for oligodeoxynucleotides (ODN) and ribozymes. The resulting interpolyelectrolyte complexes were characterized with respect to their physicochemical properties, protection efficiency against enzymatic degradation, complement activation, and biological activity under in vitro conditions. The effect of PEG molecular weight and the graft density of PEG blocks on complex characteristics was studied with two different series of block copolymers.

Efficiency of polyethylenimines and polyethylenimine-graft-poly (ethylene glycol) block copolymers to protect oligonucleotides against enzymatic degradation.

Enzymatic instability of oligonucleotides (ON) is one of the major drawbacks of this new class of therapeutic agents. The development of safe, efficient delivery systems capable of stabilizing and protecting these molecules within the formulation, as well as during application, is a challenge in modern gene therapy. In the present study, polyethylenimine (PEI) of different molecular weights and PEGylated PEI block copolymers (PEI-g-PEG) were investigated with regard to their protective properties when complexes with chemically unmodified DNA (d-ON) and RNA (r-ON) oligonucleotides.

Pegylated polyethylenimine-Fab' antibody fragment conjugates for targeted gene delivery to human ovarian carcinoma cells.

Specific targeting of ovarian carcinoma cells using pegylated polyethylenimine (PEG-PEI) conjugated to the antigen binding fragment (Fab') of the OV-TL16 antibody, which is directed to the OA3 surface antigen, was the objective of this study. OA3 is expressed by a majority of human ovarian carcinoma cell lines. To demonstrate the ability of the PEG-PEI-Fab' to efficiently complex DNA, an ethidium bromide exclusion assay was performed.

Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine.

Low-molecular-weight polyethylenimine (LMW-PEI) was synthesized by the acid-catalyzed, ring-opening polymerization of aziridine and compared with commercially available high-molecular-weight PEI (HMW-PEI) of 25 kDa. Molecular weights were determined by size-exclusion chromatography in combination with multi-angle laser light scattering. The weight average molecular weight (M(w)) of synthesized LMW-PEI was determined as 5.

Copolymers of ethylene imine and N-(2-hydroxyethyl)-ethylene imine as tools to study effects of polymer structure on physicochemical and biological properties of DNA complexes.

A series of five poly[(ethylene imine)-co-N-(2-hydroxyethyl-ethylene imine)] copolymers with similar molecular weights and different degrees of branching was established to study structure-function relationship with regard to physicochemical and biological properties as gene delivery systems. Copolymers were synthesized by acid-catalyzed ring-opening copolymerization of aziridine and N-(2-hydroxyethyl)-aziridine in aqueous solution and characterized by GPC-MALLS, (1)H- and (13)C NMR, IR, potentiometric titration, and ion exchange chromatography. Complexation of DNA was determined by agarose gel electrophoresis, and complex sizes were quantitated by PCS.

Star-shaped poly(ethylene glycol)-block-polyethylenimine copolymers enhance DNA condensation of low molecular weight polyethylenimines.

Star-shaped poly(ethylene glycol)-block-polyethylenimine [star-(PEG-b-PEI)] significantly enhance plasmid DNA condensation of low molecular weight (MW) PEIs. The star-block copolymers were prepared via a facile synthesis route using hexamethylene diisocyanate as linker between PEG and PEI blocks. NMR and FT-IR spectroscopy confirmed the structures of intermediately activated PEG and final products.

The structure of PEG-modified poly(ethylene imines) influences biodistribution and pharmacokinetics of their complexes with NF-kappaB decoy in mice.

Purpose: To study the relationship between structure of poly(ethylene imine-co-ethylene glycol), PEI-PEG, copolymers and physicochemical properties as well as in vivo behavior of their complexes with NF-kappaB decoy.

Methods: A variety of copolymers of PEG grafted onto PEI as well as PEI grafted onto PEG were synthesized and their complexes with a double stranded 20mer oligonucleotide were examined regarding size, surface charge, biodistribution and pharmacokinetics.

Results: Polyplexes of copolymers were smaller compared to polyplexes formed by non-PEGylated PEI 25 kDa (58 - 334 nm vs.

Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system.

For two series of polyethylenimine-graft-poly(ethylene glycol) (PEI-g-PEG) block copolymers, the influence of copolymer structure on DNA complexation was investigated and physicochemical properties of these complexes were compared with the results of blood compatibility, cytotoxicity, and transfection activity assays. In the first series, PEI (25 kDa) was grafted to different degrees of substitution with PEG (5 kDa) and in the second series the molecular weight (MW) of PEG was varied (550 Da to 20 kDa). Using atomic force microscopy, we found that the copolymer block structure strongly influenced the DNA complex size and morphology: PEG 5 kDa significantly reduced the diameter of the spherical complexes from 142 +/- 59 to 61 +/- 28 nm.

Poly(ethylenimine-co-L-lactamide-co-succinamide): a biodegradable polyethylenimine derivative with an advantageous pH-dependent hydrolytic degradation for gene delivery.

A biodegradable gene transfer vector has been synthesized by linking several low molecular weight (MW) polyethylenimine (PEI, 1200 Da) blocks using an oligo(L-lactic acid-co-succinic acid) (OLSA, 1000 Da). The resulting copolymer P(EI-co-LSA) (8 kDa) is soluble in water and degrades via base-catalyzed hydrolytic cleavage of amide bonds. With regard to its application as a gene transfer agent, the polymer showed an interesting pH dependency of degradation.