PEGylated PAMAM dendrimers as a potential drug delivery carrier: in vitro and in vivo comparative evaluation of covalently conjugated drug and noncovalent drug inclusion complex.

To understand more about the influence of the types of interaction between drug and PEGylated PAMAM dendrimers on the in vitro and in vivo behavior of drug, methotrexate (MTX) was coupled to PEGylated or non-PEGylated generation 4 PAMAM (G4) through complexing drug within the dendritic architecture and covalently conjugated onto the surface of the dendrimer, respectively. PAMAM was first modified with PEG(5000) chains at three different degrees of substitution. The ability of PEGylated G4 complexing MTX was higher than that of non-PEGylated one.

[PEGylated polyamidoamine dendrimer/methotrexate complex: pharmacokinetics and anti-tumor activity in normal and tumor-bearing rodents].

Generation 4 polyamidoamine (PAMAM) dendrimer was PEGylated with polyethylene glycol (PEG) at an average molecular weight 5 000 via amide bond. PAMAM and PEGylated PAMAM (PAMAM-PEG) dendrimer were used as drug nanocarriers. Methotrexate (MTX), an antineoplastic agent, was selected as a model drug.

Enhanced gene transfer into brain capillary endothelial cells using Antp-modified DNA-loaded nanoparticles.

Brain capillary endothelial cells (BCECs) have been considered as one of the primary targets for cerebral gene therapy. However, the cells, well-known for their poor function of endocytosis, are difficult to be transfected by general non-viral vectors. The aim of this study was to enhance the efficiency of transfection and expression in BCECs of DNA/polymer nanoparticles with the modification of membrane-penetrating peptide, Antennapedia peptide (Antp) polyethylenimine (PEI) and polyamidoamine (PAMAM) were chosen to prepare Antp-modified DNA-loaded nanoparticles with a complex coacervation technique.

Artificial pulmonary surfactant as a carrier for intratracheally instilled insulin.

Aim: The relative bioavailabilities and effects on lung injury alleviation of 4 insulin- artificial pulmonary surfactant (INS-APS) preparations were studied in normal rats. The relationship between the minimal surface tension (Gamma(min )) of INS-APS and the absorption of insulin was also investigated.

Methods: Four formulations of APS [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/lecithin/palmitic acid (PA), DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl), DPPC/L-alpha-phosphatidyl-DL-glycerol sodium salt (PG), DPPC/Tyl] were prepared by thin-film sonication method and direct sonication.

Tumor cell targeting of transferrin-PEG-TNF-alpha conjugate via a receptor-mediated delivery system: design, synthesis, and biological evaluation.

PEGylation is a procedure of growing interest for enhancing the therapeutic and biotechnological potential of peptides and proteins. Transferrin (Tf) has been proposed to be useful for targeting cancer cells. The aim of this study was to modify PEGylated recombinant human tumor necrosis factor alpha (PEG-TNF-alpha) with Tf to form Tf-PEG-TNF-alpha conjugates, which would maintain the advantages of PEGylation and also achieve the function of active targeting to tumor cells.

Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer.

The blood-brain barrier (BBB) poses great difficulties for gene delivery to the brain. To circumvent the BBB, we investigated a novel brain-targeting gene vector based on the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), in vitro and in vivo. Transferrin (Tf) was selected as a brain-targeting ligand conjugated to PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-Tf.

Characterization of lactoferrin receptor in brain endothelial capillary cells and mouse brain.

We present, herein, the evidence for lactoferrin (Lf) binding sites in brain endothelial capillary cells (BCECs) and mouse brain. The results from confocal microscopy showed the presence of Lf receptors on the surface of BCECs and the receptor-mediated endocytosis for Lf to enter the cells. Saturation binding analyses revealed that Lf receptors exhibited two classes of binding sites in BCECs (high affinity: dissociation constant (K (d)) = 6.

[Influence of particle size and MePEG molecular weight on in vitro macrophage uptake and in vivo long circulating of stealth nanoparticles in rats].

Aim: To investigate the influence of particle size and methoxypolyethyleneglycol (MePEG) molecular weight on the in vitro macrophage uptake and in vivo long circulating of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha)-loaded stealth nanoparticles in rats.

Methods: Three sizes (approximately 80, 70 and 240 nm) of poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (Mr 2,000, 5,000, 10,000) using the double emulsion method. The in vitro macrophage uptake and in vivo long circulating properties in rats were examined and compared.

Stealth PEG-PHDCA niosomes: effects of chain length of PEG on niosomes in vitro complement consumption and phagocytic uptake.

Aim: Poly (methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) and PHDCA niosomes were prepared and the influence of the PEG chain length on the niosomes physicochemical characteristics, complement consumption and phagocytic uptake were studied.

Methods: The physicochemical parameters of PEG-PHDCA niosomes were characterized in terms of particle size, zeta aqueous layer thickness. The relationship between physicochemical characteristics and in vitro complement consumption and phagocytic uptake was further illustrated.

In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: effect of MePEG molecular weight and particle size.

The aim of this study is to reveal the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size of stealth nanoparticles on their in vivo tumor targeting properties. Three sizes (80, 170 and 240nm) of poly methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles loading recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) were prepared at different MePEG molecular weights (MW=2000, 5000 and 10,000) using double emulsion method. The opsonization in mouse serum was evaluated by Coomassie brilliant blue staining of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

[Preparation and stability of recombinant human tumor necrosis factor-alpha-loaded stealth nanoparticles].

Aim: To prepare recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) -loaded stealth nanoparticles with different PEG chain lengths and sizes, and investigate the stability of nanoparticle suspensions.

Methods: The poly( MePEG cyanoacrylate-co-hexadecyl cyanoacrylate) (MePEG-PHDCA) and poly(hexadecyl cyanoacrylate) (PHDCA) were synthesized and characterized with Fourier transform infrared spectrum (FTIR), 1HNMR, 13CNMR and gel permeation chromatography (GPC). Uniform design was used to optimize the entrapment efficiency.

Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-alpha-loaded nanoparticles.

Aim: To study the in vitro release of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles, and investigate the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size.

Methods: Three sizes (approximately 80, 170, and 240 nm) of PEG-PHDCA nanoparticles loading rHuTNF-alpha were prepared at different MePEG molecular weights (M(r) =2000, 5000, and 10,000) using the double emulsion method. The in vitro rHuTNF-alpha release was studied in PBS and rat plasma.