Bianca Carlisi

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 interesting. This study has evidenced that the 70% of ampicillin is released quickly, while the remaining fraction is firmly incorporated in nanoparticles. The released ampicillin is quickly degraded in acid medium while the entrapped fraction is protected from acid degradation and afterwards, when nanoparticles reach the small intestine, can be readily released in the presence of esterases. This result could be exploited for the oral administration of the ampicillin-PECA system. Finally, studies of antimicrobial activity of prepared systems evidenced that ampicillin-loaded PECA nanoparticles exhibit an activity equal or higher than the free drug.

A new water-soluble synthetic polymer, α,β-polyasparthydrazide, as potential plasma expander and drug carrier

Abstract The reaction between a polysuccinimide (PSI) and hydrazine produces a water-soluble polymer α,β-polyasparthydrazide (PAHy). Tests of the polymer on laboratory animals established its potential use as a plasma substitute. Acute toxicity studies revealed no death in the animals treated, and subacute toxicity studies recorded no notable difference between treated and control animals either in terms of body-weight or the principle haematological parameters. Haemodynamic studies likewise established no significant variation in systolic and diastolic pressure or in heart beat between the two groups. Solutions of PAHy administered to bled animals improved the lowering of blood values caused by the bleeding. Moreover, PAHy was not capable of inducing any immune response when administered intradermally to laboratory animals. The potential use of PAHy as a drug carrier was also investigated. PAHy was bonded with a model drug, the antibacterial Ofloxacin, by means of a water-soluble carbodiimide, . N -ethyl-[ N ′(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC). The resulting conjugate, PAHy-Ofloxacin is, like the polymeric carrier, water-soluble and contains a quantity of linked drug equivalent to 9% (w/w).

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 dimyristoylphosphatidylcholine (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 the hydrogel was compared with the dissolution of drug solid form by examining the effects exerted on the thermotropic behaviour of the DMPC unilamellar vesicles. The transferred drug and the release rate were affected by the drug loading as well as by the pH of the external medium. In particular the release was not linearly related to the drug loading but an intermediate loading allowed a better release at both investigated pHs, with a faster and more complete release observed at pH 7.4.

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.

Polymeric prodrugs: α,β-poly(N-hydroxyethyl)-dl-aspartamide as a macromolecular carrier for some non-steroidal anti-inflammatory agents

Abstract The properties as a drug carrier of the biodegradable polymer, α,β- poly (N- hydroxyethyl )- dl - aspartamide (PHEA) were investigated. Thus, naproxen- and 4-biphenylacetic acid-PHEA adducts were prepared and characterized; drug content was evaluated by both UV and elemental analysis and hydrolysis of the adducts. In vivo analgesic and anti-inflammatory tests indicated that the adducts retain an activity comparable to that of the free drugs.

Water-soluble copolymers of an antiviral agent: synthesis and their interaction with a biomembrane model

Abstract Amantadine was modified by direct acylation with succinic and glutaric anhydrides and the covalent bond with α,β-poly( N -hydroxyethyl)-DL-aspartamide (PHEA) was realized. The amount of amantadine in the obtained copolymers was evaluated by hydrolysis of the conjugates. The enthalpic effect due to the interaction between the two synthesized polymeric prodrugs and sodium dodecylsulphate micelles as a simple system mimicking the cellular membrane, was measured by the calorimetric technique and compared with that of PHEA. Binding of PHEA-succinylamantadine (PHEA-S-AMA) to surfactant micelles appeared to be stronger than that shown by PHEA-glutarylamantadine (PHEA-G-AMA).

Interaction of macromolecular pro-drugs with lipid model membrane: calorimetric study of 4-biphenylacetic acid linked to α,β-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 drug able to suppress the phase transition was estimated by plotting the enthalpy changes of the transition vs mole ratio of added drug, and extrapolating to ΔH = 0. The trend in the ΔH values yields a possible 1 : 1 stoichiometry for the interaction between drug and phospholipid. Experiments carried out at different pH values provided information about the species involved in the interaction with DPPC liposomes. Similar results can be expected in the case of the cell membrane.

pH-sensitive hydrogel based on a polyaspartamide derivative

A pH-sensitive hydrogel was prepared by UV irradiation technique. Starting polymer was obtained from α,β-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 prepared network as a pH-sensitive drug delivery system, propionyl-L-carnitine, chosen as a model drug, was entrapped into this hydrogel both during the irradiation process and after cross-linking reaction by a soaking technique. In vitro release studies showed that the drug release rate depends on the different swelling of the network as a function of the environmental pH as well as on the different drug loading method.

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 thermal analysis. A peculiar effect of the degree of cross-linking on the glass transition temperature (T g ) value was shown. In vitro chemical and enzymatic stability studies suggested that the prepared samples do not undergo any degradation alter treatment at pH 1. 7.4 and 10 as well as after incubation with enzymes such as peptin and α-chymotrypsin.

Calorimetric investigation of the interaction between α,β-poly(N-hydroxyethyl)-DL-aspartamide and surfactants

Abstract The enthalpic effect due to the interaction between α,β- poly (N- hydroxyethyl )- dl -aspartamide (PHEA) and sodium dodecyl sulfate, cetyltrimethylammonium bromide, and Octylphenoxypolyethoxyethanol in aqueous solutions, as a function of the surfactant concentration, was measured by the Calorimetric technique. Below the critical micellar concentration, no enthalpic effect was measured. At higher concentrations, the enthalpic effect, exothermic for the interaction of PHEA with the anionic micelles and endothermic for that with the cationic and nonionic micelles, was interpreted in terms of the binding of micelles to the polymeric chain. The influence of a simple electrolyte (sodium chloride) on the PHEA-micelle interaction was also investigated and is discussed here.