Biomedical subjects

Federica Chiellini

Publications and source records attributed to Federica Chiellini.

8 recordsLinked to original sources

PubMed2006

Biocompatibility and degradation of aliphatic segmented poly(ester amide)s: in vitro and in vivo evaluation.

Aliphatic segmented poly(ester amide)s, comprising a crystallizable amide phase and a flexible amorphous ester phase, were investigated for potential use in biomedical applications. By varying the amide content and the type of crystallizable amide segments, the polymer's thermal and mechanical properties can readily be tuned. Polymers with 25 and 50 mol % of amide content are noncytotoxic and sustain growth of fibroblasts onto polymer films. The in vitro degradation of these polymers was followed in PBS (pH 7.4) at 37 degrees C up to 7 months. The poly(ester amide)s showed the characteristics of bulk degradation with a gradual decrease in molecular weight and almost no mass loss. The in vivo degradation of these polymers, followed by subcutaneous implantation in rats up to 6 weeks, was slow and similar to the in vitro degradation. The tissue response upon implantation was followed over 6 weeks. A mild foreign-body reaction, characterized by the presence of macrophages, and sporadically a lymphocyte, were observed in the first week of implantation. After 6 weeks the implant site is characterized by fibrous encapsulation with no signs of inflammation. The poly(ester amide)s tested are biocompatible, but their in vitro as well as in vivo degradation is very slow.

Amides↗

PubMed2006

Polymer-based biodegradable drug delivery systems in pain management.

Pain is an unpleasant sensory experience commonly produced by damage to bodily tissues and it is one of the most significant public health problems, because 21.5% of the world population is estimated to suffer from pain. It results in a total loss of more than 165 billion US dollars each year in the United States alone. Pain reflects a mixture of various pathophysiologic, psychologic, and genetic contributions. When undertreated, pain usually results in serious immune and metabolic upset. Therefore, it requires wide understanding and intensive effort for a better management. Currently, pain control is limited by the modest efficiency of the used drugs, the serious side effects of these drugs, and the inefficacy of conventional drug administration. By the introduction of the technology of biodegradable controlled-release devices into clinical practice, pain control not only benefits from these novel methods for a better delivery of various drugs, but the side effects of the drugs are reduced because use of the devices improves patient compliance. Biodegradable controlled-release devices are polymer-based devices that are designed to deliver drugs locally in a predesigned manner. Recently, there was a high interest in developing these devices for the delivery of different drugs used for pain control. This paper first highlights the dimensions and basics of the problem of pain. Then, it presents an overview of the biodegradable polymers that are used in drug delivery systems and summarizes the studies carried out on these systems in the field of pain management. We refer to our experience in developing a device for multimodal drug delivery, including the use of nanotechnology. Future perspectives are also presented.

Absorbable Implants↗

PubMed2005

Novel poly(amido-amine)-based hydrogels as scaffolds for tissue engineering.

Biodegradable and biocompatible amphoteric poly(amido-amine) (PAA)-based hydrogels, containing carboxyl groups along with amino groups in their repeating unit, were considered as scaffolds for tissue engineering applications. These hydrogels were obtained by co-polymerising 2,2-bisacrylamidoacetic acid with 2-methylpiperazine with or without the addition of different mono-acrylamides as modifiers, and in the presence of primary bis-amines as crosslinking agents. Hybrid PAA/albumin hydrogels were also prepared. The polymerisation reaction was a Michael-type polyaddition carried out in aqueous media. The PAA hydrogels were soft and swellable materials. Cytotoxicity tests were carried out by the direct contact method with fibroblast cell lines on the hydrogels both in their native state (that is, as free bases) and as salts with acids of different strength, namely hydrochloric, sulfuric, acetic and lactic acid. This was done in order to ascertain whether counterion-specific differences in cytotoxicity existed. It was found that all the amphoteric PAA hydrogels considered were cytobiocompatible both as free bases and salts. Selected hydrogels samples underwent degradation tests under controlled conditions simulating biological environments, i.e. Dulbecco medium at pH 7.4 and 37 degrees C. All samples degraded completely and dissolved within 10 d, with the exception of hybrid PAA/albumin hydrogels that did not dissolve even after eight months. The degradation products of all samples turned to be non-cytotoxic. All these results led us to conclude that PAA-based hydrogels have a definite potential as degradable matrices for biomedical applications.

Animals↗

PubMed2004

End-functionalised 1-vinyl-2-pyrrolidinone oligomers bearing lactate functions at one end.

1-Vinyl-2-pyrrolidinone (VP) oligomers bearing a lactate group at one end (PVP-L) were obtained by chain-transfer controlled radical polymerisation carried out in the presence of ethyl L-lactate as chain-transfer agent (CTA). Their number-average molecular weights were in the range 1500-4000 with molecular weight distributions ranging from 1.4 to 1.8. The chain transfer constant, C(T), of the ethyl L-lactate/VP system was determined by monitoring the variation of PVP-L number-average molecular weight on conversion. The C(T) value so obtained was 1.03 x 10(-2), which is by about one order of magnitude higher than the C(T) value previously determined for a seemingly similar system, namely methyl isobutyrate/1-vinyl-2-pyrrolidinone (1.64 x 10(-3)). The resultant PVP-L oligomers were thoroughly characterised by means of (1)H and (13)C NMR, in order to ascertain the regular presence of the lactate functions at one of their chain terminals. NMR characterisations gave results in full agreement with the proposed structure. Moreover, the molecular weight values determined by NMR very closely agreed with those obtained by SEC. Preliminary biological evaluations of the PVP-L oligomers showed a complete lack of toxicity.

Animals↗

PubMed2004

Environmentally degradable bio-based polymeric blends and composites.

Blends and composites based on environmentally degradable-ecocompatible synthetic and natural polymeric materials and fillers of natural origin have been prepared and processed under different conditions. Poly(vinyl alcohol) (PVA) was used as the synthetic polymer of choice by virtue of its capability to be processed from water solution or suspension as well as from the melt by blow extrusion and injection molding. Starch and gelatin were taken as the polymeric materials from renewable resources. The fillers were all of natural origin, as waste from food and agro-industry consisted of sugar cane bagasse (SCB), wheat flour (WF), orange peels (OR), apple peels (AP), corn fibres (CF), saw dust (SD) and wheat straw (WS). All the natural or hybrid formulations were intended to be utilized for the production of: a) Environmentally degradable mulching films (hydro-biomulching) displaying, in some cases, self-fertilizing characteristics by in situ spraying of water solutions or suspensions; b) Laminates and containers to be used in agriculture and food packaging by compression and injection molding followed by baking. Some typical prototype items have been prepared and characterized in relation to their morphological and mechanical properties and tested with different methodology for their propensity to environmental degradation and biodegradation as ultimate stage of their service life. A relationship between chemical composition and mechanical properties and propensity to biodegradation has been discussed in a few representative cases.

Biodegradation, Environmental↗

PubMed2004

Design of highly specific ligands of fibrin for therapeutic applications.

The work presented here is aimed at designing high-affinity ligands for the fibrin gamma (312-324) epitope. This epitope is specific for fibrin recognition, as it is exposed only on the fibrin surface, while in fibrinogen it is buried in the protein bulk. This property makes it very useful for therapeutic applications. In fact, it may be exploited in driving systems for targeted delivery of thrombolytic drugs toward the specific compartment where they are needed. It will then allow avoidance of serious unwanted side effects produced by a conventional systemic administration. The approach chosen for designing putative ligands is based on the known three-dimensional (3D) structure of the epitope. A wide virtual library made up of oligo-peptides and analogues designed by a combinatorial approach, on the basis of chemical complementarity criteria, has been screened by means of a docking/scoring approach (DOCK program). The peculiarity of the problem under study required a considerable effort in finding a method enabling the experimental validation of the design work results. In fact the selected biological target is absolutely new, so that neither a endogenous, nor a synthetic high-affinity ligand is known up to now. It does not allow for the validation of computational results by means of classical binding tests based on the use of known labeled high-affinity ligands. Preliminary binding essayes were so carried out by means of the Plasmon Surface Resonance (PSR) technique. The experimental results suggested that most of the molecules predicted to be good ligands by means of the selected computational tools, could carry the wanted affinity toward the selected target.

Amino Acid Sequence↗

PubMedDate not supplied

Novel agmatine-containing poly(amidoamine) hydrogels as scaffolds for tissue engineering.

Novel biocompatible and biodegradable amphoteric poly(amidoamine) (PAA) hydrogels were designed for applications as scaffolds for tissue engineering. These hydrogels (PAA-AG1 and PAA-AG2) were obtained by polyaddition of 2,2-bisacrylamidoacetic acid with 2-methylpiperazine and 4-aminobutyl guanidine, a bioactive molecule with a known ability to induce adhesion to cell membranes. They contain carboxylic functions in their main chain and interchain connections deriving from two different cross-linking agents: for PAA-AG1, a multifunctional primary amine, that is, 1,10-decanediamine; for PAA-AG2, a purposely synthesized PAA (PAA-NH(2)) containing pendant NH(2). Both PAA-AG1 and PAA-AG2 proved noncytotoxic and adhesive to cell membranes, as ascertained by means of cytotoxicity and proliferation tests carried out on fibroblast cell lines. Good apparent mechanical strength was also observed in the case of PAA-AG2, cross-linked with the PAA-NH(2). Both PAA-AG1 and PAA-AG2 underwent degradation tests under controlled conditions simulating the biological environments, that is, Dulbecco medium at pH 7.4 and 37 degrees C. They completely dissolved within 10 and about 40 days, respectively. In both cases, the degradation products were completely noncytotoxic. All the results of this paper point to the conclusion that agmatine-based PAA hydrogels are excellent substrates for cell proliferation.

3T3 Cells↗

PubMedDate not supplied

Bioerodible polymeric nanoparticles for targeted delivery of proteic drugs.

Significant efforts are being devoted to develop nanotechnology for drug delivery, mainly because of the distinct advantages offered by nanometer-size polymeric systems. Moreover, targeted drug delivery can be obtained by polymer conjugation to biospecific ligands. The present investigation was aimed mainly at determining the targeting ability of hybrid nanoparticles based on synthetic polymer/protein hybrid matrices. These nanoparticles were designed for liver targeted release of proteic drugs with antiviral activity, such as alpha-interferon. Human serum albumin and the monoesters of alternating copolymers of maleic anhydride/alkyl vinyl ethers of oligo(ethylene glycol) were selected as proteic and synthetic components, respectively. Digalactosyl diacyl glycerol, a natural glycolipid selectively recognized by the asialofetuin receptor present on liver hepatocytes was used as active targeting agent. Nanoparticles of 100-300 nm average size were obtained by controlled coprecipitation method. Investigation of nanoparticle surface properties by spectroscopic analysis and by biological tests indicated that the synthesized nanoparticles do expose on their surface targeting moieties that selectively interact with liver hepatocytes receptors.

Animals↗