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Biomedical subjects

F Pavanetto

Publications and source records attributed to F Pavanetto.

At least 19 recordsLinked to original sources
PubMed2005

Preparation and in vitro evaluation of thiolated chitosan microparticles.

The objective of this study was to prepare a microparticulate drug delivery system being based on a new thiomer, namely a chitosan 2-iminothiolane conjugate (chitosan-TBA conjugate). Due to thiol groups being immobilized on chitosan, chitosan-TBA conjugate exhibits improved mucoadhesive and permeation enhancing properties. Because of these features microparticulate drug delivery systems based on chitosan-TBA conjugate might be a promising tool for the non-invasive administration of hydrophilic macromolecular drugs. Chitosan-TBA conjugate microspheres were prepared by the emulsification/solvent evaporation method. Fluorescein-isothiocyanate labelled dextran (FITC-dextran) was chosen as a model hydrophilic drug. Microspheres have been characterized by morphological analysis, thiol group content, swelling behaviour, polymer degradation drug load determination, dissolution test and mucoadhesion studies. Results reported in this work demonstrated the possibility to obtain stable microspheres without cross-linking agents. Thiolated chitosan microspheres seem to be more stable in aqueous media with respect to unmodified chitosan. The degradability by lysozyme appears quite similar for both polymers, showing that chemical modification does not influence the biodegradable properties of chitosan. Microspheres were able to control the drug release for at least 1 h, exhibiting comparatively strong mucoadhesive properties. The chitosan-TBA conjugate microparticles remain on the mucosa in a 2.5-fold higher concentration with respect to unmodified chitosan microparticles. These data suggest that chitosan-TBA conjugate microspheres have the potential to be used as a mucoadhesive drug delivery system.

Adhesiveness↗
PubMed2004

Biodegradable microspheres for prolidase delivery to human cultured fibroblasts.

Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for which there is not, as yet, a resolutive cure. We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared, modifying the classical double emulsion solvent evaporation method to mitigate the burst effect of the enzyme from the microspheres. Ex-vivo experiments were performed, by incubating microencapsulated prolidase with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to the cells. The microparticulate drug delivery system described carried small amounts of active prolidase inside fibroblasts, ensuring a response to the intracellular accumulation of X-Pro dipeptides, the mechanism that is supposed to be responsible for the development of clinical manifestations of this disorder in man. A positive result of the presence of active enzyme inside cells was an improvement in fibroblast shape.

Biodegradation, Environmental↗
PubMed2003

PLGA microspheres for oral osteopenia treatment: preliminary "in vitro"/"in vivo" evaluation.

The aim of this work was to prepare and to evaluate "in vitro"/"in vivo" microspheres based on poly(D,L-lactide-co-glycolide) copolymers containing ipriflavone, for the local treatment of oral bone loss. The first objective was the preparation and "in vitro" characterization of ipriflavone loaded microspheres, by emulsion/solvent evaporation method. Process parameters such as drug:polymer weight ratio, and molecular weight of copolymers, were also investigated. The second objective was to elaborate a suitable animal model of mandibular osteoporosis, to evaluate the efficacy of these microparticulate drug delivery systems. "In vivo" experiments were carried out on female rats, in which oral osteopenia was induced by gonadectomy and molar avulsion. Morphometric analysis of mandibular segment were carried out to quantify the development of oral osteopenia and the efficacy of drug loaded microspheres. Results showed that ipriflavone loaded PLGA microspheres can be successfully obtained with good "in vitro" characteristics, utilizing the emulsification/solvent evaporation method. "In vivo" experiments revealed that local administration of microspheres produced only mild inflammation on the injection site. Morphometric analyses showed, at the level of the third molar, a slight increase in spongy and total bone mass on rat jaw treated with microspheres with respect to control. Control animals exhibited a scarce degree of osteopenia demonstrating that this animal model is not suitable for this purpose.

Animals↗
PubMed2003

Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug.

The aim of the present work was to design a film dosage form for sustained delivery of ipriflavone into the periodontal pocket. For this purpose, monolayer composite systems made of ipriflavone loaded poly(D,L-lactide-co-glycolide) (PLGA) micromatrices in a chitosan film form, were obtained by emulsification/casting/evaporation technique. Multilayer films, made of three layers of polymers (chitosan/PLGA/chitosan), were also prepared and compared to monolayer films for their "in vitro" characteristics. Morphology and physico-chemical properties of the different systems were evaluated. The influence of pH, ionic strength and enzymatic activity on film degradation, was also investigated. Significant differences in swelling, degradation and drug release were highlighted, depending on film structure and composition. In vitro experiments demonstrated that the composite micromatricial films represent a suitable dosage form to prolong ipriflavone release for 20 days.

Chitin↗
PubMed2002

Effect of nanoparticle encapsulation on the photostability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate.

The aim of this study was to investigate the influence of nanoparticle-based systems on the light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC). Ethylcellulose (EC) and poly-D,L-lactide-co-glycolide (PLGA) were used as biocompatible polymers for the preparation of the particulate systems. The "salting out" method was used for nanoparticle preparation and several variables were evaluated in order to optimize product characteristics. The photodegradation of the sunscreen agent in emulsion vehicles was reduced by encapsulation into the PLGA nanoparticles (the extent of degradation was 35.3% for the sunscreen-loaded nanoparticles compared to 52.3% for free trans-EHMC) whereas the EC nanoparticle system had no significant effect. Therefore, PLGA nanoparticles loaded with trans-EHMC improve the photostability of the sunscreen agent.

Cellulose↗
PubMed2001

Enzyme loaded biodegradable microspheres in vitro ex vivo evaluation.

Prolidase is a naturally occurring enzyme involved in the final stage of protein catabolism. Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. Although several attempts have been made towards the treatment of this pathology, a cure for this disease has yet to be found. The purpose of this work is to evaluate the possibility of enzyme replacement therapy through prolidase microencapsulation in biodegradable microspheres. The poly(D,L-lactide-co-glycolide) (PLGA) prolidase loaded microparticulate systems have been prepared utilizing the w-o-w double emulsion solvent evaporation method. They have been characterized "in vitro" by morphological analysis, total protein content and an in vitro dissolution test of active protein. "Ex vivo" evaluation of prolidase activity from the microspheres has been performed on cellular extracts of cultured skin fibroblasts from healthy subjects (controls) and from patients affected by PD. The results reported in this work on prolidase from pig kidney (available on the market) demonstrate the positive role of microencapsulation as a process of enzymatic activity stabilization inside PLGA microspheres achieving both in vitro and ex vivo active enzyme release. This formulation can be proposed as a parenteral depot drug delivery system.

Adult↗
PubMed2001

Long-term release of clodronate from biodegradable microspheres.

This paper describes the formulation of a biodegradable microparticulate drug delivery system containing clodronate, a bisphosphonate intended for the treatment of bone diseases. Microspheres were prepared with several poly(D,L-lactide-co-glycolide) (PLGA) copolymers of various molecular weights and molar compositions and 1 poly(D,L-lactide) (PDLLA) homopolymer by a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation procedure. Critical process parameters and formulation variables (ie, addition of stabilizing agents) were evaluated for their effect on drug encapsulation efficiency and clodronate release rate from microparticles. Well-formed clodronate-loaded microspheres were obtained for all polymers by selecting suitable process parameters (inner water/oil volume ratio 1:16, temperature-raising rate in the solvent evaporation step 1 degree C/min, 2% wt/vol NaCl in the external aqueous phase). Good yields were obtained in all batches of clodronate microspheres (above 60%); drug encapsulation efficiencies ranged between 49% and 75% depending on the polymer used. Clodronate release from all copolymer microspheres was completed in about 48 hours, while those from PDLLA microspheres required about 20 days. The change of microsphere composition by adding a surfactant such as Span 20 or a viscosing agent such as carboxymethylcellulose extended the long-term release up to 3 months. Clodronate was successfully entrapped in PLGA and PDLLA microspheres, and drug release could be modulated from 48 hours up to 3 months by suitable selection of polymer, composition, additives, and manufacturing conditions.

Biodegradation, Environmental↗
PubMed2000

Study on glycolic acid delivery by liposomes and microspheres.

Glycolic acid is used in many cosmetic products as exfoliant and moisturizer. Unfortunately, the greater glycolic acid cosmetic benefits the greater is the potential for skin irritation as far as burning. The aim of this work was to investigate the feasibility of topical controlled delivery systems loading glycolic acid in order to optimize the acid cosmetic properties lowering its side effects. For this purpose different types of microparticulate systems have been evaluated: liposomes, liposomes modified by chitosan addition and chitosan microspheres. Liposomes, composed of phosphatidylcholine and cholesterol (1:1 molar ratio) and with different glycolic acid/lipid molar ratio, were prepared by reverse phase evaporation method. Two types of interaction between liposomes and chitosan were investigated: chitosan addition into lipidic bilayer during liposome preparation and coating of already formed liposomes with chitosan. Glycolic acid loaded chitosan microspheres were prepared by the dry-in-oil emulsion method. The microparticulate systems were morphologically characterized by electron microscopy and particle size analysis. In vitro dissolution tests were performed to evaluate the feasibility of microparticulate systems in modulating glycolic acid release. The results obtained show that liposomes are always suitable to modulate glycolic acid release and that the best condition to achieve this control is obtained by the liposomal systems in which glycolic acid/lipid molar ratio is 5:1. Further significant release control is obtained by addition of chitosan into the liposomes, while chitosan microspheres are not able to control glycolic acid release even after crosslinking.

Administration, Topical↗
PubMed1999

Microparticulate drug delivery systems.

Chitosan was proposed as a drug carrier for mucosal administration in ocular, buccal, nasal, gastroenteric and vaginal-uterine therapies based on its bioadhesive properties and biodegradability in vivo under the action of hydrolases. Examples are the delivery of acyclovir via ocular administration, and the delivery of 5-aminosalicylic acid to the colon. Microparticles may need to be cross-linked to retard their degradation in acidic media; yet cross-linking with glutaraldehyde introduces cytotoxic characteristics and depresses bioadhesion. Alternative cross-linking approaches are discussed along with the suitability of chitosan for the oral delivery of vaccines.

Acyclovir↗
PubMed1998

Different molecular weight chitosan microspheres: influence on drug loading and drug release.

Influence of chitosan molecular weight on drug loading and drug release of drug-loaded chitosan microspheres was studied. Chitosans of 70,000 (LC), 750,000 (MC), and 2,000,000 (HC) molecular weight were employed alone or as mixtures (HC/LC 1:1-1:2 w/w). Ketoprofen (ket) was chosen as the model drug to be encapsulated. Microspheres characterized by different theoretical polymer/drug ratios were prepared (2:1, 1:1, 1:2 w/w). Satisfactory ket contents were obtained for all batches of chitosan microspheres with the theoretical polymer/drug ratio 1:2 w/w; microspheres made of HC/LC (1:2 w/w) were characterized by good drug content and encapsulation efficiency independent by polymer/drug ratio. Prepared chitosan microparticulate delivery systems can modulate ket release within 48 hr. Microspheres consisting of HC/LC (1:2 w/w) were the most suitable formulation in controlling drug release.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Bioadhesive microspheres for ophthalmic administration of acyclovir.

The bioavailability of acyclovir to the ophthalmic epithelium is low and when the drug is administered in ophthalmic ointment it must be applied every four hours. An emulsification technique has been used to prepare acyclovir-loaded chitosan microspheres with the aim of promoting the prolonged release of drug and increasing its ocular bioavailability. The microparticulate drug-delivery systems obtained have been characterized for their morphology and physicochemical characteristics by in-vitro dissolution tests and in-vivo ocular administration to rabbits. The results show that the microspheres obtained are always quite small--the diameters of 90% of the particles are < or = 25 microns (i.e. d 90% never exceeds 25 microns) and physicochemical characterization shows that the drug is homogeneously dispersed in an amorphous state inside the microspheres. The in-vitro dissolution profile of acyclovir from chitosan microspheres is slower than that for the raw drug. Results from in-vivo ocular administration of acyclovir-loaded microspheres to the rabbit eye show prolonged high concentrations of acyclovir and increased AUC values. The microparticulate drug-carrier seems a promising means of topical administration of acyclovir to the eye.

Acyclovir↗
PubMed1994

Antigravitropic activity of 2-(2-arylamino-1,2-dioxoethyl) benzoic acid methyl esters.

Methylation of 1,3-dihydro-1-hydroxy-3-oxo-1-isobenzofurancarboxamides (A-I) yields 2-(2-arylamino-1,2-dioxoethyl)benzoic acid methylesters. The esters 1-7 allowed the evaluation of the intrinsic activity of 2-(2-arylamino-1,2-dioxoethyl)benzoic structure, to whom the antigravitropic effect of the carboxamides A-I may be probably assigned. The comparison of activities of methylesters 1-7 (B) and 8-14 (C) shows how conformational differences as those between the arylamino-1,2-dioxoethylic portion of B and the arylamino-2-oxoethylic portion of C may deeply effect phytotropin interaction with the receptor site.

Benzoates↗
PubMed1989

Particulate matter test in small volume parenterals: critical aspects in sampling methodology.

The following critical steps of the particulate matter test sampling methodology for small volume parenteral products (SVPs), conduct by light blockage method, were considered: 1) reliability of the small volume aspirator sampler for different sample volumes; 2) particulate matter distribution inside each ampoule in liquid products (8 liquid SVPs tested); 3) influence of the sample preparation method on the evaluation of the final contamination of the sample. Nine liquid SVPs were tested by preparing samples following the three U.S.P. XXI methods: 1) unit as it is (direct analysis), II) unit diluted, III) sample obtained by combining several units. Particles counts were performed by a HIAC/ROYCO model 3000 counter fitted with a small volume sampler. The validation of the sampler shows that it should be improved. A more accurate and strict validation than the one stated by U.S.P. XXI is suggested. The particulate matter distribution in liquid products is found to be uniform inside the ampoule in the size range greater than or equal to 2 microns-greater than or equal to 10 microns; the analysis can be performed examining only a portion of the whole content. The three sample preparation methods lead to significantly different contamination results. The particulate control test should be conduct by direct analysis, as it is carried out under the same conditions as for product use. The combining method (III) is suggested for products of less than 2 ml volume that cannot be examined by direct analysis.

Drug Contamination↗
PubMed1986

Evaluation of official instrumental methods for the determination of particulate matter contamination in large volume parenteral solutions.

The distribution pattern of particle contamination in nine different types of LV parenteral solutions and the possibility of correlating the counts made with two official instruments (Coulter Counter and HIAC) were studied. Two hundred containers of LV parenteral solutions (corresponding to 40 batches) produced in Italy, were sampled. Each bottle was submitted to HIAC and Coulter Counter countings, for particle sizes ranging between 2 and 25 micron. For about 50% of the products, the two straight lines that represent the distribution of particle contamination obtained with the two methods did not cross-over within the studied size range, the Coulter Counter counts always proving higher than the HIAC ones. In the other cases, the cross-over point of the two lines occurred at varying size levels. Statistical analysis of the results pointed to a relationship between the contamination values obtained with the two counting methods for sizes ranging between 2 and 5 micron, but there was no correlation for sizes equal to, or higher than, 10 micron. From the maximum contamination levels established by the BP and the FU IX for the HIAC method, the corresponding values were calculated for the Coulter Counter method. Similarly the values were calculated the HIAC method based on the maximum values set for the Coulter Counter.

Drug Contamination↗
PubMed1985

Antimycotic 2-alkyldithio, 2-aralkyldithio, 2-aryldithiobenzamides.

Some 2-alkyldithio, 2-aralkyldithio, 2-aryldithio benzoic acids, their methyl esters and N-monosubstituted amides were prepared and tested in vitro against Candida albicans and Trichophyton mentagrophytes. Some N-monosubstituted amides displayed activities similar to those of clotrimazole and pyrrolnitrin. Against Candida albicans, N-monosubstituted amides exhibited a generally higher activity than the corresponding N-monosubstituted amides of 2,2'-dicarboxydiphenyldisulfide.

Amides↗
PubMed1984

[Derivatives of 2-thiocyanobenzoic acid with antifungal activity].

A series of amides, esters and thioesters of 2-thiocyanobenzoic acid were synthesised and tested for antifungal activity in vitro and in vivo against various strains of fungus pathological to plants. The phytotoxicity against representative plants was studied in parallel. The substances were prepared by condensation of suitable mercaptobenzamides with cyanogen bromide or of 2-thiocyanobenzoyl chloride with amines, alcohols or mercaptans. This research showed in vitro antifungal activity of some N-monosubstituted amides and in vivo activity of some N-monosubstituted and N,N-disubstituted amides of 2-thiocyanobenzoic acid which have the same protective activity towards P. viticola as Zineb.

Animals↗