Search results for "Polymers."
showing 10 items of 3543 documents
Balancing Passive and Active Targeting to Different Tumor Compartments Using Riboflavin-Functionalized Polymeric Nanocarriers
2017
Riboflavin transporters (RFTs) and the riboflavin carrier protein (RCP) are highly upregulated in many tumor cells, tumor stem cells, and tumor neovasculature, which makes them attractive targets for nanomedicines. Addressing cells in different tumor compartments requires drug carriers, which are not only able to accumulate via the EPR effect but also to extravasate, target specific cell populations, and get internalized by cells. Reasoning that antibodies are among the most efficient targeting systems developed by nature, we consider their size (-10-15 nm) to be ideal for balancing passive and active tumor targeting. Therefore, small, short-circulating (10 kDa, -7 nm, t1/2 - 1 h) and large…
HPMA-LMA copolymer drug carriers in oncology: an in vivo PET study to assess the tumor line-specific polymer uptake and body distribution.
2013
Polymeric drug carriers aim to selectively target tumors in combination with protecting normal tissue. In this regard polymer structure and molecular weight are key factors considering organ distribution and tumor accumulation of the polymeric drug delivery system. Four different HPMA based copolymer structures (random as well as block copolymers with lauryl methacrylate as hydrophobic block) varying in molecular weight, size and resulting architecture were analyzed in two different tumor models (AT1 prostate carcinoma and Walker-256 mammary carcinoma) in vivo. Polymers were labeled with (18)F and organ/tumor uptake was followed by μPET imaging and ex vivo biodistribution. Vascular permeabi…
Selective Inhibition of Human Natural Killing and Antibody-Dependent Cellular Cytotoxicity by a Polyanion
1987
A high molecular polyanion, Liquoid, was found to inhibit at nontoxic concentrations (12-50 micrograms/ml) the natural killing (NK) and the antibody-dependent cellular cytotoxic (ADCC) activity of human peripheral blood mononuclear cells selectively. Whereas NK of the K 562 target cell was slightly or not at all affected, the spontaneous lysis of PDe-B-1, an EBV-transformed B-cell line, was strongly inhibited or even completely abolished. ADCC activity could only be inhibited by Liquoid if the target cells were mycoplasma-free, while the polyanion had no effect when mycoplasma-contaminated target cells were used. Liquoid did not alter the target binding capacity of the NK effector cells and…
Fate of Linear and Branched Polyether-Lipids In Vivo in Comparison to Their Liposomal Formulations by 18F-Radiolabeling and Positron Emission Tomogra…
2015
In this study, linear poly(ethylene glycol) (PEG) and novel linear-hyperbranched, amphiphilic polyglycerol (hbPG) polymers with cholesterol (Ch) as a lipid anchor moiety were radiolabeled with fluorine-18 via copper-catalyzed click chemistry. In vivo investigations via positron emission tomography (PET) and ex vivo biodistribution in mice were conducted. A systematic comparison to the liposomal formulations with and without the polymers with respect to their initial pharmacokinetic properties during the first hour was carried out, revealing remarkable differences. Additionally, cholesterol was directly labeled with fluorine-18 and examined likewise. Both polymers, Ch-PEG27-CH2-triazole-TEG-…
Therapy of Peritoneal Murine Cancer with Biological Response Modifiers
1985
We have used a murine renal adenocarcinoma of spontaneous origin (Renca) inplanted in the peritoneal cavity to study the therapeutic potential of biological response modifiers (BRMs) used alone or in conjunction with chemotherapy. This tumor model is therapeutically challenging since following intraperitoneal (i.p.) injection, the tumor grows progressively with hemorrhagic ascites, abdominal metastases to lymph nodes, liver, spleen, most serous membranes, and, in some animals, metastases to extra-abdominal sites (lungs). In the absence of therapy, death invariably occurs within 36 +/- 2 days. The tumor is efficiently lysed in 4 hours by peritoneal cells isolated from mice treated with BRMs.…
INULIN BASED HYDROGEL FOR ORAL DELIVERY OF FLUTAMIDE: PREPARATION, CHARACTERIZATION AND IN VIVO RELEASE STUDIES
2012
The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH = 7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal ac…
Extended release and enhanced bioavailability of moxifloxacin conjugated with hydrophilic cellulose ethers.
2015
Macromolecular prodrugs (MPDs) of moxifloxacin were fabricated based on hydroxypropylcellulose (HPC) and hydroxyethylcellulose (HEC). UV/Vis spectrophotometry was employed to determine covalently loaded drug content (DC) of each conjugate. The degree of substitution (DS) of moxifloxacin attained ranged from 0.27 to 0.38 (HPC) and 0.19 to 0.26 (HEC) per anhydroglucose unit (AGU), respectively. Transmission electron microscopic analyses showed that HPC-moxifloxacin conjugates self-assembled into nanowires of ∼ 30 nm diameters while HEC-moxifloxacin conjugates self-assembled into nanoparticles of 150-350 nm. In vitro drug release studies revealed that 15 and 49% moxifloxacin release occurred f…
Polyhydroxyethylaspartamide-based micelles for ocular drug delivery
2009
In this paper three copolymers of polyhydroxyethylaspartamide (PHEA), bearing in the side chains polyethylene glycol (PEG) and/or hexadecylamine (C(16)) (PHEA-PEG, PHEA-PEG-C(16) and PHEA-C(16) respectively) have been studied as potential colloidal drug carriers for ocular drug delivery. The physical characterization of all three PHEA derivatives, using the Langmuir trough (LT) and micellar affinity capillary electrophoresis (MACE) techniques allowed to assume that whereas alone PHEA backbone is an inert polymer with respect to the interactions with lipid membranes and drug complexation, when PHEA chains are grafted with long alkyl chains like C(16) or in combination C(16) chains and hydrop…
Influence of polymer molecular weight on in vitro dissolution behavior and in vivo performance of celecoxib:PVP amorphous solid dispersions
2016
In this study, the influence of the molecular weight of polyvinylpyrrolidone (PVP) on the non-sink in vitro dissolution and in vivo performance of celecoxib (CCX):PVP amorphous solid dispersions were investigated. The dissolution rate of CCX from the amorphous solid dispersions increased with decreasing PVP molecular weight and crystallization inhibition was increased with increasing molecular weight of PVP, but reached a maximum for PVP K30. This suggested that the crystallization inhibition was not proportional with molecular weight of the polymer, but rather there was an optimal molecular weight where the crystallization inhibition was strongest. Consistent with the findings from the non…
Comparison of Active and Passive Targeting of Docetaxel for Prostate Cancer Therapy by HPMA Copolymer–RGDfK Conjugates
2011
N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel-RGDfK conjugate was synthesized, characterized, and evaluated in vitro and in vivo in comparison with untargeted low and high molecular weight HPMA copolymer-docetaxel conjugates. The targeted conjugate was designed to have a hydrodynamic diameter below renal threshold to allow elimination post treatment. All conjugates demonstrated the ability to inhibit the growth of DU145 and PC3 human prostate cancer cells and the HUVEC at low nanomolar concentrations. The targeted conjugate showed active binding to α(v)β(3) integrins in both HUVEC and DU145 cells, whereas the untargeted conjugate demonstrated no evidence of specific binding. …