Search results for "Prodrug"
showing 10 items of 89 documents
Prodrug based on halloysite delivery systems to improve the antitumor ability of methotrexate in leukemia cell lines
2021
The prodrug approach, as well as the development of specific systems able to deliver a chemotherapeutic agent in the target site, decreasing the side effects often associated with its administration, are still a challenging. In this context, both methotrexate drug molecules (MTX) and biotin ligand moieties, whose receptors are overexpressed on the surface of several cancer cells, were loaded on halloysite nanotubes (HNTs) to develop nanomaterial based on multifunctional and "smart" delivery systems. To highlight the crucial role played by biotin, carrier systems based on HNTs and MTX were also synthetized. In detail, several approaches were envisaged: i) a supramolecular interaction between…
Potential dopamine prodrug-loaded liposomes: preparation, characterization, andin vitrostability studies
2010
Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of the blood-brain barrier (BBB). Condensation of dopamine with neutral amino acids could afford potential pro- drugs able to interact with the BBB endogenous transporters and easily enter the brain. To improve the bio-availability of the dopamine prodrug, 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DOPH), it was encapsulated in unilamellar liposomes of dimiristoylphosphatidylcholine (DMPC)and cholesterol. Vesicles were characterized by dynamic light scattering in order to evaluate their dimensions and vesicle stability, by zeta-potential measurements, by means of electronic mi…
Anticancer Activity, Reduction Mechanism and G-Quadruplex DNA Binding of a Redox-Activated Platinum(IV)–Salphen Complex
2022
Aiming at reducing the unselective cytotoxicity of Pt(II) chemotherapeutics, a great deal of effort has been concentrated into the design of metal-containing drugs with different anticancer mechanisms of action. Inert Pt(IV) prodrugs have been proposed to be a valid alternative as they are activated by reduction directly into the cell releasing active Pt(II) species. On the other hand, a promising strategy for designing metallodrugs is to explore new potential biological targets rather than canonical B-DNA. G-quadruplex nucleic acid, obtained by self-assembly of guanine-rich nucleic acid sequences, has recently been considered an attractive target for anticancer drug design. Therefore, comp…
Calorimetric investigation of the interaction between a macromolecular prodrug of diflunisal and human platelets
1995
The thermal effect due to the interaction between human platelets and α,β poly(N-hydroxy-ethyl)-DL-aspartamide (PHEA) or the PHEA-Diflunisal conjugate was measured by the calorimetric technique at 25°C. The experimental data confirm that PHEA is a biocompatible macromolecule and that its conjugate influences the physiological activity of human platelets.
Macromolecular Prodrugs Based on Synthetic Polyaminoacids: Drug Delivery and Drug Targeting in Antitumor Therapy
2011
In the last twenty years a depth study on potential pharmaceutical applications of synthetic polymers at proteinlike structure as carrier for macromolecular prodrug production has been performed in academia and in industry. In particular α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), α,β-polyaspartylhydrazide (PAHy), poly(glutamic acid) (PGA), poly(aspartic acid) (PAA) and polylysine (PLL) have been extensively studied in this field. In the present review, the use of PHEA, PAHy, PGA as starting materials to prepare macromolecular prodrugs is reported and drug delivery and targeting aspects have been considered.
Synthesis and in vitro studies on a potential dopamine prodrug.
2008
Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Conden- sation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is de- scribed. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log P …
Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.
2013
Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver…
Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of the bladder: Phase I-II study on marker lesions
2004
Abstract Objectives To study the ablative activity of intravesical gemcitabine against superficial transitional cell carcinoma of the bladder at different doses and concentrations. Methods A total of 27 patients were treated with intravesical gemcitabine after transurethral resection during which one to three papillary marker lesions were left unresected. Starting 14 days after transurethral resection, six instillations of gemcitabine were given at weekly intervals. Gemcitabine, diluted in 50 mL of saline solution and maintained for 2 hours, was given at the dose of 500 mg, 1000 mg, and 2000 mg in groups of 9 patients each. A complete response (CR) was defined as negative cytology, cystosco…
Pharmacokinetics and absolute bioavailability of oral cefuroxime axetil in the rat.
2000
The objectives of this study were to determine the oral bioavailability of cefuroxime (C) and to evaluate the pharmacokinetic model that best describes the plasma concentration behaviour following single intravenous (IV), intraperitoneal (IP) and oral single doses. The same dose of C was administered by IV, IP and oral routes to three separate groups of rats (2.02 mg of cefuroxime axetil (CA) by the oral route or 1.78 mg of cefuroxime sodium (CNa) by IV and IP route). A two-compartment open model without lag time can predict the C disposition kinetics. The influence of the administration route on the pharmacokinetic parameters and AUC values was investigated by means of a one-way analysis o…
SYNTHESIS, PHYSICO-CHEMICAL AND BIOLOGICAL CHARACTERIZATION OF A PACLITAXEL MACROMOLECULAR PRODRUG
2004
Paclitaxel was attached to poly(hydroxyethylaspartamide) via a succinic spacer arm by a two-step protocol: (1) synthesis of 2'-O-succinyl-paclitaxel; (2) synthesis of PHEA-2'-O-succinyl-paclitaxel. The 2'-O-succinyl-paclitaxel derivative and the macromolecular conjugate were characterized by UV, IR, NMR and mass spectrometry analysis. The reaction yields were over 95% and the purity of products over 98%. Paclitaxel release and degradation from 2'-O-succinyl-paclitaxel occurred at a faster rate at pH 5.5 than 7.4. After 30 h of incubation at pH 5.5 and 7.4 the released free paclitaxel was about 40 and 20%, respectively. In plasma both drug release and degradation were found to occur at a hig…