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Biomedical subjects

G Giammona

Publications and source records attributed to G Giammona.

At least 19 recordsLinked to original sources
PubMed2004

Drug release from alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide-based microparticles.

Spherical pH-sensitive microparticles have been prepared by reverse phase suspension polymerization technique. Starting polymer has been alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) has been crosslinked in the presence of acrylic acid (AA) or methacrylic acid (MA) at various concentration. The obtained microparticles have been characterized by FT-IR spectrophotometry, particle size distribution analysis and scanning electron microscopy. In order to have information about water affinity of the prepared samples, swelling measurements have been carried out in aqueous media which simulate some biological fluids. The possibility to employ the prepared samples as pH-sensitive microparticles has been investigated by performing in vitro release studies. Experimental data have showed that the release rate from these microparticles depends on the environmental pH and the chemical structure of the drug.

Absorption↗
PubMed2004

Synthesis, physico-chemical and biological characterization of a paclitaxel macromolecular prodrug.

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 higher rate than in buffer at pH 7.4 suggesting that an enzymatic mechanism could be involved. The paclitaxel release and degradation from PHEA-2'-O-succinyl-paclitaxel were negligible at pH 5.5 and 7.4 and very slow in plasma. Investigation carried out using murine myeloid cell line showed that the polymeric prodrug maintains partial pharmacological activity of paclitaxel. The DL50 of the conjugate (over 40 ng/ml) as compared to free paclitaxel (about 1 ng/ml) was correlated to the slow drug release. Finally a pharmacokinetic study carried out by intravenous inoculation of the macromolecular prodrug to mice demonstrated that the polymer conjugation modify dramatically the in vivo fate of the drug. The conjugate disappeared from the bloodstream much more quickly as compared to both free drug and naked polymer. Massive accumulation of bioconjugate in the liver (80% of the dose) was found to persist throughout 1 week.

Animals↗
PubMed2003

Biodegradable hydrogels obtained by photocrosslinking of dextran and polyaspartamide derivatives.

The functionalization of dextran with glycidyl methacrylate (GMA) leads to the formation of a derivative that generates hydrogels for irradiation at 365nm. The effects of various polymer concentrations and irradiation times on the yield and the properties of the obtained hydrogels are reported. The networks have been characterized by FT-IR spectra, dimensional analysis and swelling measurements carried out at different pH values. In vitro studies suggest that all samples undergo a partial chemical hydrolysis, whereas the incubation with dextranases causes a total degradation whose rate depends on the degree of crosslinking. In addition, aqueous solutions of functionalized dextran have been irradiated in the presence of PHG (PHEA-GMA), i.e. the copolymer obtained by the reaction of alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with GMA. The crosslinking reaction leads to the formation of new networks containing both polymers whose properties have been investigated. To evaluate the processes which occur during UV irradiation, the sol fractions have been purified and characterized by FT-IR and 1H-NMR analyses. Finally, the suitability of hydrogels deriving from functionalized dextran, crosslinked alone or in the presence of PHG, for drug delivery systems has been investigated choosing theophylline as a model drug.

Biocompatible Materials↗
PubMed2001

alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers (PAHy-GTA): novel polymers with potential for DNA delivery.

Hydrophilic polycations form complexes when mixed with plasmids. Following functionalisation with glycidyltrimethylammonium chloride (GTA) alpha,beta-poly(asparthylhydrazide) (PAHy), a water-soluble synthetic macromolecule, becomes polycationic and potentially useful for systemic gene delivery. Initially the biocompatibility of PAHy and PAHy-GTA derivatives with different degrees of positive charge substitution were studied and it was shown that PAHy-GTA was neither haemolytic nor cytotoxicity up to 1 mg/ml. After intravenous injection (125)I-labelled PAHy-GTA derivative containing 46 mol% (PAHy-GTA(b)) of trimethylammonium groups did not accumulate in the liver (4.1+/-0.9% of the recovered dose after 1 h) but was subjected to renal excretion (45+/-21% of the recovered dose was in the kidneys after 1 h). PAHy-GTA formed complexes with DNA (gel retardation) and they protected against degradation by DNase II. Finally the ability of the PAHy-GTA(b) derivative to mediate the transfection of HepG2 cells using the marker gene beta-galactosidase was studied. The optimum plasmid/polymer mass ratio was examined in comparison to LipofectACE, Lipofectin and polyethylenimine.

Animals↗
PubMed2001

Synthesis and biopharmaceutical characterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers.

Four new poly(hydroxyethylaspartamide)-based copolymers bearing (a) poly(ethylene glycol) 2000, (b) poly(ethylene glycol) 5000, (c) poly(ethylene glycol) 2000 and hexadecylalkyl, (d) poly(ethylene glycol) 5000 and hexadecylalkyle, as pendant groups were synthesised. The copolymers were obtained by partial aminolysis of polysuccinimide with poly(ethylene glycol) and hexadecylalkyl amino derivatives followed by reaction with ethanolamine. Naked polyhydroxyaspartamide was obtained by polysuccinimide reaction with ethanolamine. The nuclear magnetic resonance, infrared, light scattering and elemental analysis allowed for the extensive physico-chemical characterisation of the carriers. The molecular mass of all the polymers was in the range of 27000-34000 Da, and the polydispersivity was in the range of 1.5-1.7. By intravenous injection to mice bearing a solid tumour, all the polymeric carriers displayed a bi-compartmental pharmacokinetic behaviour. Both the poly(ethylene glycol) and the hexadecylalkyle conjugation prolonged and enhanced the distribution phase of poly(hydroxyethylaspartamide). The poly(ethylene glycol) conjugation was found to promote the carrier elimination by kidney ultrafiltration and to prevent partially the accumulation in the spleen and in the liver. The poly(ethylene glycol)/hexadecylalkyle conjugates localised preferentially in the liver were over 30% of the dose/g of tissue was determined after 144 h from administration. In the tumour all the polymers displayed a relevant accumulation that significantly increased throughout the time to reach high concentrations after 24 h. In particular, the poly(ethylene glycol)/hexadecylalkyle conjugates achieved a concentration of 15-25% of the dose/g of tissue after 24 h from administration that was maintained up to 144 h.

Animals↗
PubMed2001

Ocular tolerability and in vivo bioavailability of poly(ethylene glycol) (PEG)-coated polyethyl-2-cyanoacrylate nanosphere-encapsulated acyclovir.

Acyclovir-loaded polyethyl-2-cyanoacrylate (PECA) nanospheres were prepared by an emulsion polymerization process in the micellar phase and characterized. The influence of the presence of nonionic surfactant as well as other substances [i.e., 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and poly(ethylene glycol) (PEG)], on formulation parameters and loading capacity was investigated. In particular, the presence of PEG resulted in an increase of mean size and size distribution. To obtain PEG-coated PECA nanospheres with a mean size of < 200 nm, Pluronic F68 at concentrations > 1.5% (w/v) should be used during preparation. The presence of PEG also resulted in a change in zeta potential, from -25.9 mV for uncoated nanospheres to -12.2 mV for PEG-coated PECA nanospheres. The presence of HP-beta-CyD elicited an increase of nanosphere size and size distribution, but zeta potential was not influenced. In vitro drug release from nanospheres was determined in both phosphate buffer (pH 7.4) and plasma. The presence of HP-beta-CyD and PEG did not influence the acyclovir release rate in plasma. In the case of release in phosphate buffer, PEG-coated nanospheres showed a slower release. Ocular tolerability of PEG-coated PECA nanospheres was evaluated by the in vivo Draize test. This colloidal carrier was well tolerated, eliciting no particular inflammation at the level of the various ocular structures. In vivo ocular bioavailability was evaluated by instilling 50 microL of the acyclovir-loaded nanospheres only once in the conjunctival sac of rabbit eyes. At various time intervals, aqueous humour acyclovir content was determined by high-performance liquid chromatography. Acyclovir-loaded PEG-coated PECA nanospheres were compared with an aqueous solution of the drug and a physical mixture of acyclovir nanospheres. The acyclovir-loaded PEG-coated PECA nanospheres showed a significant (p < 0.001) increase of drug levels (25-fold) in aqueous humor compared with the free drug or the physical mixture. This finding is probably due to an improved ocular mucoadhesion of PEG-coated PECA nanospheres.

Acyclovir↗
PubMed2001

Amoxicillin-loaded polyethylcyanoacrylate nanoparticles: influence of PEG coating on the particle size, drug release rate and phagocytic uptake.

Polyethyleneglycol (PEG)-coated polyethylcyanoacrylate (PECA) nanoparticles loaded with amoxicillin were prepared and the influence of the PEG coating on the particle size, zeta potential, drug release rate and phagocytic uptake by murine macrophages was studied. Experimental results show that this colloidal drug delivery system could be useful for intravenous or oral administration. The profile of amoxicillin release from PECA nanoparticles system was studied under various conditions similar to those of some corporeal fluids. In all these experiments, amoxicillin release in the free form was studied by HPLC analysis. Experimental results showed that at pH 7.4 drug release rises when molecular weight of PEG added to polymerization medium increases; in human plasma on the contrary drug release is reduced as molecular weight of PEG rises. Phagocytosis was evaluated by incubating amoxicillin-loaded PECA nanoparticles with murine macrophages and determining the amount of phagocytized nanoparticles by dosing the amoxicillin present inside the macrophages. The results of this study showed significative differences between nanoparticles prepared in the presence or in the absence of PEG and demonstrated that the PEG coating reduces the macrophages uptake. These results suggest that nanoparticles prepared in the presence of PEG are stealth carriers, which could be an injectable colloidal system able to avoid MPS recognition after intravenous injection. Experimental data of drug release at pH 1.1 and in the presence of urease, taking into account the mucoadhesive properties of polyalkylcyanoacrylate nanoparticles and the activity of the amoxicillin versus Helicobacter pylori, suggest moreover that the colloidal drug delivery system obtained in our laboratory could be useful for the treatment of diseases caused by H. pylori by peroral administration.

Amoxicillin↗
PubMed2000

Influence of different parameters on drug release from hydrogel systems to a biomembrane model. Evaluation by differential scanning calorimetry technique.

A comparative study on the drug release capacity of four water swellable polymeric systems was carried out by differential scanning calorimetry (DSC). The polymeric systems chosen were alpha,beta-polyaspartahydrazide (PAHy) crosslinked by glutaraldehyde (GLU) (PAHy-GLU) or by ethyleneglycoldiglycidylether (EGDGE), (PAHy-EGDGE), polyvinylalcohol (PVA) crosslinked by glutaraldehyde (PVA-GLU) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) by gamma irradiation (PHEA-gamma matrices). The degree of crosslinking for PAHy-GLU, PAHy-EGDGE and PVA-GLU samples was about 0.4 and 0.8. These hydrogels were characterized as free of drugs and were loaded with diflunisal (DFN) (approximately 2.5% w/w). Diflunisal, a non-steroidal anti-inflammatory drug, has been chosen as a model drug to be incorporated into polymeric matrices to follow the release processes of a drug from these hydrogels to a model membrane made by unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). Differential scanning calorimetry appears to be a suitable technique to follow the transfer kinetics of the drug from the controlled release system to the biomembrane model. The drug releases from all the considered polymeric hydrogels, were compared with the release observed from the drug solid form by examining the effects on the thermotropic behaviour of DPPC unilamellar vesicles. The release kinetics of the drug from hydrogels were followed at 25, 37 and 50 degrees C to evidence the influence of temperature on the drug release and on the successive transfer to biological membrane model. Particularly, it appears evident that the total amount of drug transferred and the release rate are affected by the polymer crosslinking degree (it increases with crosslinking decrease) as well as by the nature of crosslinking agent. In fact, the drug release profiles from PAHy-GLU samples are more differentiated than those from PAHy-EGDGE. The effect of parameters correlating with the properties of starting polymer, such as water-affinity, crystallinity, glass-to-rubber transition temperature and affinity towards drug molecules, has been also evaluated.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Studies of macromolecular prodrugs of zidovudine.

The current problems in controlling severe viral infections such as AIDS as well as the lack of effective and safe therapeutic measures for such diseases have caused interest in systems such as macromolecular prodrugs potentially able to solve heavier drawbacks of conventional antiviral therapy. This review focuses on various approaches proposed in the literature in this field. Neoglycoproteins and synthetic protein-like structure polymers have been mainly proposed. In the first group, the possibility of incorporating into the polymeric structures a determined amount of sugar molecules make them interesting candidates for targeting of infected blood cells. The conjugate of zidovudine (AZT) and an anti-transferrin receptor antibody OX-26 has been proposed for brain targeting. The conjugate of AZT with alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) showed good release properties in a prolonged time.

Journal Article↗
PubMed1999

New biodegradable hydrogels based on a photocrosslinkable modified polyaspartamide: synthesis and characterization.

alpha,beta-Poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), a synthetic water-soluble biocompatible polymer, was derivatized with glycidyl methacrylate (GMA), in order to introduce in its structure chemical residues having double bonds and ester groups. The obtained copolymer (PHG) contained 29 mol% of GMA residues. PHG aqueous solutions at various concentrations ranging from 30 to 70 mg/ml were exposed to a source of UV rays at lambda 254 nm in the presence or in the absence of N,N'-methylenebisacrylamide (BIS); the formation of compact gel phases was observed beginning from 50 mg/ml. The obtained networks were characterized by FT-IR spectrophotometry and swelling measurements which evidenced the high affinity of PHG hydrogels towards aqueous media at different pH values. In vitro chemical or enzymatic hydrolysis studies suggested that the prepared samples undergo a partial degradation both at pH 1 and pH 10 and after incubation with enzymes such as esterase, pepsin and alpha-chymotrypsin. Finally, the effect of irradiation time on the yield and the properties of these hydrogels was investigated and the sol fractions coming from irradiated samples, properly purified, were characterized by FT-IR and 1H-NMR analyses.

Acrylamides↗
PubMed1999

New biodegradable hydrogels based on an acryloylated polyaspartamide cross-linked by gamma irradiation.

Alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), a synthetic biocompatible macromolecule, was functionalized with glycidyl methacrylate (GMA) in order to introduce in its side chains residues having double bonds and ester groups. The copolymer (PHG), obtained from PHEA and GMA, had a degree of derivatization of 29 mol%. PHG aqueous solutions are cross-linked by gamma radiation at 0 degrees C either in the presence or absence of N,N'-methylenebisacrylamide (BIS) giving rise to new hydrogel systems. In both cases gelation occurs at quite low doses (0.26 and 0.4 kGy, respectively). The obtained networks were characterized by FT-IR spectrophotometry which confirmed that the cross-linking process involves the vinyl groups of the polymer chains. Swelling measurements evidenced the high affinity of aqueous media at different pH-values towards PHG hydrogels. The sol fractions of the irradiated samples, properly purified, were characterized by FT-IR and 1H-NMR analyses and reduced viscosity measurements. Finally, in vitro chemical or enzymatic hydrolysis studies suggested that the prepared samples undergo a partial degradation at pH 1 and 10 or after incubation with enzymes such as esterase, pepsin, and alpha-chymotrypsin.

Biocompatible Materials↗
PubMed1998

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 in plasma than in aqueous buffer solutions. These results show that after i.v. administration this drug-polymer conjugate can release zidovudine into the blood circulation for prolonged periods.

Anti-HIV Agents↗
PubMed1998

Swellable microparticles containing Suprofen: evaluation of in vitro release and photochemical behaviour.

Suprofen, an anti-inflammatory drug was incorporated in polymer networks based on biocompatible macromolecules, such as alpha,beta-polyasparthydrazide (PAHy) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) crosslinked by glutaraldehyde or gamma-rays, respectively. Swelling tests carried out in aqueous media showed that pH value affects the swelling degree of the prepared hydrogels. In vitro release tests were performed in simulated gastrointestinal fluids (pH 1/6.8) using the pH variation method and in phosphate-buffered saline, pH 7.4. Experimental data indicated that Suprofen was released in a sustained way both from PAHy and PHEA microparticles. Further, incorporation of Suprofen in PAHy and PHEA networks provided a significant reduction of the drug photosensitizing activity, as evidenced by in vitro hemolysis tests.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

A hydrogel based on a polyaspartamide: characterization and evaluation of in-vivo biocompatibility and drug release in the rat.

This paper deals with the characterization of a new microparticulate hydrogel obtained by gamma irradiation of alpha, beta-poly[N-(2-hydroxyethyl)-DL-aspartamide] (PHEA). When enzymatic digestion of PHEA hydrogel was evaluated using various concentrations of pepsin and alpha-chymotrypsin no degradation occurred within 24 h. In-vivo studies showed that this new material is biocompatible after oral administration to rats. PHEA hydrogel was also studied as a system for delivery of diflunisal, an anti-inflammatory drug. In-vitro release studies in simulated gastrointestinal juice (pH 1 or 6.8) showed that most of the drug was released at pH 6.8. In-vivo studies indicated that diflunisal-loaded PHEA microparticles significantly improved the gastric tolerance and oral bioavailability of the drug in comparison with free diflunisal. These results suggest the potential application of PHEA hydrogel as a new delivery system for the oral administration of anti-inflammatory drugs.

Administration, Oral↗
PubMed1997

Cervical epidural abscess: serial MRI study.

Cervical epidural abscess (CEA) at first often goes unrecognized and it is to be suspected in patients suffering by spinal ache, root pain, neurological deficit and fever. Staphylococcus aureus is the most frequent etiologic agent. At present MRI is the study of choice for the diagnosis of CEA. We suggest a serial MRI study in close time in at first doubtful cases of CEA. When the responsible organism is not identified and there are also compressive signs of the spinal cord, the treatment of choice is surgical decompression followed by selective antibiotic therapy. The duration of antibiotic therapy may be established not only by clinical judgement, but also by serial MRI study, which gives direct information about disease evolution.

Abscess↗