Reaction of α,β-poly(N-hydroxyethyl)-DL-aspartamide with derivatives of carboxylic acids

pH-sensitive hydrogel based on a novel photocross-linkable copolymer.

A pH sensitive hydrogel has been prepared by a UV irradiation technique. Starting polymer was the PHM (poly hydroxyethylaspartamide methacrylated) obtained from polyaspartamide (PHEA) partially derivatized with methacrylic anhydride (MA). This new copolymer has been further derivatized with succinic anhydride (SA) to obtain PHM-SA that has been cross-linked by UV irradiation to form a pH sensitive hydrogel. The network, recovered after washing as a powder, has been been characterized by FT-IR spectrophotometry and particle size distribution analysis. Moreover, to have information about water affinity of the prepared sample, swelling measurements have been carried out in aqueous media mimick…

Composite nanoparticles based on hyaluronic acid chemically cross-linked with alpha,beta-polyaspartylhydrazide.

In this paper, new composite nanoparticles based on hyaluronic acid (HA) chemically cross-linked with alpha,beta polyaspartylhydrazide (PAHy) were prepared by the use of a reversed-phase microemulsion technique. HA-PAHy nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence of the chemical cross-linking, dimensional analysis, and transmission electron micrography, showing a sub-micrometer size and spherical shape. Zeta potential measurements demonstrated the presence of HA on the nanoparticle surface. A remarkable affinity of the obtained nanoparticles toward aqueous media that simulate some biological fluids was found. Stability studies showed the absence of chem…

Synthesis of polymeric derivatives of isoniazid: characterization and in vitro release from a water-soluble adduct with polysuccinimide.

Coupling of isoniazid with polysuccinimide afforded a water-insoluble polymeric pro-drug; by reaction with ethanolamine it was chemically transformed in a water-soluble adduct. The in vitro release of isoniazid from the drug-polymer adduct was studied by using an artificial stomach wall lipid membrane. The transfer rate constant from simulated gastric juice to simulated plasma was defined and compared with that of an equivalent dose of pure drug.

Addition reactions of azoesters with 2-thioquinazolinones

Reaction between diethyl azodicarboxylate (I) and 1,2,3,4-tetrahydro-2-thioquinazolin-4-one (II), as a cyclic model of thiourea, both in alcoholic medium and in inert solvents has been investigated. By carrying out the reaction in an inert solvent, it was possible to isolate an intermediate. Evidence is presented that the intermediate, in turn, was converted into the final products. Structures were unequivocally assigned by mass spectrometry.

Evaluation of polyalkylcyanoacrylate nanoparticles as a potential drug carrier: preparation, morphological characterization and loading capacity.

Some physicochemical behaviours were investigated of polyethyl- (PECA) and polyisobutylcyanoacrylate (PICA), which, in recent years, have been proposed as nanoparticle colloidal systems for drug carrying. We observed the influence of preparation conditions, such as pH value and surfactant concentration, on parameters such as particle size and polymer molecular weight. Lower operating pH values (0-2) resulted in smaller nanoparticles than those prepared at pH 5.5. The polymer molecular weight was also a function of pH: low molecular weight at low pH and vice-versa. The surfactant concentration positively influenced main particle size and polymer molecular weight. These trends were independen…

Reactions of azoesters and dimethyl acetylenedicarboxylate with 3-methyl-1,2,4-triazole-5-thione

The addition of dimethyl acetylenedicarboxylate to 3-methyl-1,2,4-triazole-5-thione (1), both in alcoholic medium and in inert solvents, has been investigated. When 1 was allowed to react with diethyl azodicarboxylate a disulfide 5 was obtained.

DIFFERENTIAL SCANNING CALORIMETRY STUDY ON DRUG RELEASE FROM AN INULIN-BASED HYDROGEL AND ITS INTERACTION WITH A BIOMEMBRANE MODEL:pH AND LOADING EFFECT

Inulin has been derivatized with methacrylic anhydride (MA) and succinic anhydride (SA) to obtain a methacrylated/succinilated derivative (INU-MA-SA) able to produce a pH sensitive hydrogel after UV irradiation. The hydrogel was characterized and loaded with diflunisal (10.4, 17 and 24%, w/w) chosen as a model drug. The drug release from INU-MA-SA-based hydrogel to a biomembrane model made by unilamellar vesicles of dimyristoylphosphatidyl-choline (DMPC) was investigated at pH 4.0 and 7.4 by differential scanning calorimetry (DSC) that appears to be a suitable technique to follow the transfer kinetics of a drug from a controlled release system to a biomembrane model. The drug release from t…

Novel hydrogels based on a polyasparthydrazide. Synthesis and characterization

α,β-polyasparthydrazide (PAHy), a synthetic water-soluble biocompatible polymer, was chemically crosslinked with ethyleneglycol diglycidylether (EGDGE), in order to obtain water swellable microparticies. These were characterized by means of FT-IR spectrophotometry and by means of particle size distribution analysis. The mean pore size of the prepared gels as various crosslinking ratios and the fractal dimensions were determined by light scattering measurements. Swelling measurements gave evidence of the high affinity of PAHy-EGDGE microparticles towards aqueous media at different pH values. The physical state of the prepared networks was evaluated by means of X-rays diffractometry and therm…

Novel cationic polyaspartamide with covalently linked carboxypropyl-trimethyl ammonium chloride as a candidate vector for gene delivery

Abstract The non-viral gene vector properties of a protein-like polymer, the α,β-poly(N-2-hydroxyethyl)- d , l -aspartamide (PHEA) were investigated after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing cationic groups, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with hydrazide pendant groups by reaction with hydrazine monohydrate (HYD), obtaining the polyhydrazide α,β-poly(N-2-hydroxyethyl/carbazate)- d , l -aspartamide (PHEA–HYD). In this paper we reported that polymer functionalization degree can be easily modulated by varying reaction conditions, so allowing us to produce two PHEA derivatives…

Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles.

In this paper, the experimental conditions for preparing ampicillin-loaded polyethylcyanoacrylate (PECA) nanoparticles are described. The effects of drug concentration and surfactant type in the polymerization medium on the particle size distribution and loading capacity were studied. The results of these studies show that only the type of surfactant has an impact on the nanoparticle dimensions. The release rate of ampicillin from PECA nanoparticles at pH 7.4 (extracellular value pH) performed either with and without esterases, show that the drug release is considerably increased in the presence of these exzymes. The results of drug release study at pH 1.1 (simulated gastric juice) are very…

INTERACTION OF MACROMOLECULAR PRO-DRUGS WITH LIPID MODEL MEMBRANE - CALORIMETRIC STUDY OF 4-BIPHENYLACETIC ACID LINKED TO ALPHA,BETA-POLY(N-HYDROXYETHYL)-DL-ASPARTAMIDE INTERACTING WITH PHOSPHATIDYLCHOLINE VESICLES

The effect of 4-biphenylacetic acid (BPAA) covalently linked to α,β-poly(N-hydroxyethyl)-dl-aspartamide (PHEA) on the thermotropic properties of dipalmitoylphosphatidylcholine (DPPC) liposomes was investigated by differential scanning calorimetry (DSC). Addition of increasing amounts of PHEA-BPAA adduct to a suspension of phospholipid vesicles modified the thermotropic gel-to-liquid crystalline phase transition by decreasing the enthalpy changes ΔH with concomitant broadening of the peak without variations in the transition temperature (Tm). These effects are interpreted in terms of a deep interaction of BPAA bound to the polymer with the apolar moiety of the lipid bilayer. The amount of dr…

pH-sensitive hydrogel based on a polyaspartamide derivative

A pH-sensitive hydrogel was prepared by UV irradiation technique. Starting polymer was obtained from alpha,beta-poly (N-2-hydroxyethyl)-DL-aspartamide (PHEA) partially derivatized with glycidyl methacrylate (PHG). The PHG copolymer was cross-linked by UV irradiation in the presence of methacrylic acid (MA) to form a pH sensitive hydrogel. The cross-linked matrix shaped as microparticles was characterized by FT-IR spectrophotometry, XPS, X-ray diffraction, SEM and particle size distribution analyses. Moreover, to have information about water affinity of the prepared sample, swelling measurements were carried out in aqueous media mimicking some biological fluids. In order to employ the prepar…

Preparation and Biological Evaluation of Ethylcellulose Microspheres Containing Tolmetin

AbstractTolmetin microspheres were prepared by the coacervation process from the ethylcellulose. Microspheres were obtained both in presence and without protecting colloids, such as polyisobutilene (PIB) or ethyl-vinylacetate copolimers (EVA). The effect of these agents on the preparation, drug content, wall thickness, surface morphology, drug dissolution arid release from microspheres, were evaluated. The dissolution rate analysis was carried out also in the presence of a surfactant (Tween 80) at different pH values.In addition, microspheres containing Tolmetin as a core material were submitted to biological tests, in comparison with the free drug, to evaluate upon experimental models the …

Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies.

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater …

Hydrophilic and Hydrophobic Polymeric Derivatives of Anti-Inflammatory Agents Such as Alclofenac, Ketoprofen, and Ibuprofen

Macromolecular prodrugs of a hydrophilic polymer [α,β-poly( N- hydroxyethyl)-DL-aspartamide (PHEA)] was used as a drug carrier. Three poly- (HEA)-NSAID adducts were studied: poly(HEA)-Alclofenac, poly(HEA)-Keto profen, and poly(HEA)-Ibuprofen. Prodrugs with different drug content were synthesized both as water-soluble and water-insoluble agents. Hydrolysis of water-soluble adducts in a simulated gastric juice was studied.

Crosslinked α,β-Polyasparthydrazide Micromatrices for Controlled Release of Anticancer Drugs

The preparation of new hydrogels by the reaction of α,β- polyasparthydrazide and glutaraldehyde is reported. A different crosslinking degree was obtained by varying the ratio crosslinking agent/polymer which influenced the swelling behavior of the gel. 5-Fluorouracil, was incorporated into the matrices during the crosslinking reaction and in vitro release studies were performed in simulated gastric juice (pH 1.1) and pH 7.4 buffer solution. The hydrogels prepared were chemically stable in the dissolution media. The observed data show the potential application of these new matrices for peroral administration of anticancer agents.