Luciana Sartore

Enzyme modification by MPEG with an amino acid or peptide as spacer arms

A method for the modification of enzymes by MPEG carrying an amino acid or peptide as a spacer arm is described and tested with aliphatic or aromatic side chains amino acids. The procedure involves MPEG activation byp-nitrophenylchloroformate for the amino acid or peptide coupling that is in turn activated for the protein binding.The advantage of the method resides in the possibility to introduce proper reporter groups between the polymer and the protein as norleucine for a direct evaluation of the bound polymer chains, tryptophan for structural studies of the polymer-protein adduct, and radioactive amino acid for pharmacokinetic investigations.The method was positively tested with arginase, ribonuclease, and superoxide dismutase as enzymes of therapeutic value.

RECENT RESULTS ON FUNCTIONAL POLYMERS AND MACROMONOMERS OF INTEREST AS BIOMATERIALS OR FOR BIOMATERIAL MODIFICATION

Different families of functionalized polymers with potential as biomaterials, or for biomaterial modification, have been investigated. In particular, degradation studies have been performed on poly(amidoamines), a family of polymers obtained by polyaddition of amines to bisacrylamides, and endowed with heparin-complexing ability. Some new poly(amidoamines) with more resistance towards hydrolytic degradation than traditional ones have been discovered. Other ter-amino polymers deriving from the polyaddition of ter-amino functionalized bis-thiols to bis-acrylic esters, or other activated unsaturated compounds, have been studied. Their quaternarization products have been proven, in a parallel work, to act as powerful antimicrobial agents. By performing in situ the polyaddition reaction, semi-interpenetrated networks based on silicone rubber and the same polymers have been prepared. Finally, end-functionalized amphiphilic oligomers have been prepared by radical polymerization techniques, and their use for enzyme modification considered.

Thermal properties of a new class of block copolymers based on segments of poly(d,l-lactic-glycolic acid) and poly(ε-caprolactone)

Abstract The results of differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic-mechanical thermal analysis (DMTA) investigations performed on a new class of multi-block copolymers based on poly( d , l -lactic-glycolic acid) (PLGA) and diol-terminated poly(e-caprolactone) (PCDT) segments are reported. The synthesis and molecular weight characterisation of these materials, having a structure of poly(ester-carbonate)s, were described in a recent paper. In the present work the influence of the length of PCDT segments and of the molar ratio between the d , l -lactic acid (LA) and glycolic acid (GA) residues on thermal stability, degree of crystallinity and glass transition temperature (Tg) has been investigated. Materials completely amorphous or having variable degrees of crystallinity have been obtained modulating the above parameters. The TGA traces run under nitrogen atmosphere exhibit two degradation processes that can be ascribed to the PLGA and PCDT segments, respectively. In addition, the thermal-stability increases with the LA content in the PLGA blocks.

Autonomic Self-Healing in Epoxidized Natural Rubber

The development of polymers that can repair damage autonomously would be useful to improve the lifetime of polymeric materials. To date, limited attention has been dedicated to developing elastomers with autonomic self-healing ability, which can recover damages without need for an external or internal source of healing agents. This work investigates the self-healing behavior of epoxidized natural rubber (ENR) with two different epoxidation levels (25 and 50 mol % epoxidation) and of the corresponding unfunctionalized rubber, cis-1,4-polyisoprene (PISP). A self-adhesion assisted self-healing behavior was revealed by T-peel tests on slightly vulcanized rubbers. A higher epoxidation level was found to enhance self-healing. Self-healing of rubbers following ballistic damages was also investigated. A pressurized air flow test setup was used to evaluate the self-healing of ballistic damages in rubbers. Microscope (OM, SEM, and TEM) analyses were carried out to provide further evidence of healing in the impact zones. Self-healing of ballistic damages was observed only in ENR with 50 mol % epoxidation and it was found to be influenced significantly by the cross-link density. Finally, self-healing of ballistic damages was also observed in ENR50/PISP blends only when the content of the healing component (i.e., ENR50) was at least 25 wt %. From an analysis of the results, it was concluded that a synergistic effect between interdiffusion and interaction among polar groups leads to self-healing in ENR.

Thermogravimetric investigation of two classes of block copolymers based on poly(lactic-glycolic acid) and poly(ε-caprolactone) or poly(ethylene glycol)

Abstract The thermogravimetric analysis (TGA) of two classes of multi-block copolymers based on poly( d , l -lactic-glycolic acid) (PLGA) and diol-terminated poly(e-caprolactone) (PCDT) or poly(ethylene glycol) (PEG) segments is reported. These materials, having the structure of poly(ester-carbonate)s, were synthesized by a chain extension reaction. The influence of the length of PCDT or PEG segments and of the molar ratio of d , l -lactic acid (LA) and glycolic acid (GA) residues on thermal stability in air and nitrogen atmosphere has been investigated. For comparison purposes the degradation behaviour of starting oligomers was also studied. TGA under nitrogen shows two degradation processes that can be ascribed to the PLGA and PCDT or PEG segments, respectively. In addition, the thermal stability increases with the LA content in the PLGA blocks. In the tests run under air two degradation steps have also been observed, though the former occurs in general at higher temperatures.

Low Molecular Weight End-Functionalized Poly(N-Vinylpyrrolidinone) for the Modification of Polypeptide Aminogroups

New monofunctionalized amphiphilic oligomers, poly (N-vinyl pyrrolidinones) with an hydroxyl end group, were prepared by radical polymerization with 2-isopropoxyethanol, fractionated by both gel-permeation chromatography and fractional precipitation. The terminal hydroxyl group oligomers was activated and reacted with the amino groups of a model peptide, and a protein. These hydroxylated oligomers were also converted to carboxylate end group which were also activated and used as protein and peptide modifying agents.

Degradation behaviour of ionic stepwise polyaddition polymers of medical interest

The aim of this presentation is to review some of our recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest. PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides. There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioetheramine)s (PSTAs). Most of the PAAs exhibit heparin complexing ability. PAAs are also being considered as soluble carriers for delivering anti-cancer drugs. Some of these polymers have been studied as antimicrobial agents. PAAs with different structures degrade at different rates under physiological conditions. The degradation rate is also strongly influenced by pH. The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ultimately degrade to oligomeric products, while the quaternized PAAs do rapidly degrade.

Multiblock copolymers based on segments of poly (D, L-lactic-glycolic acid) and poly(ethylene glycol) or poly(∈-caprolactone): A comparison of their thermal properties and degradation behavior

A comparison of the thermal properties of two classes of poly(D,L-lactic-glycolic acid) multiblock copolymers is reported. In particular, the results of differential scanning calorimetry, and thermogravimetric analysis of copolymers containing poly(ethylene glycol) (PEG) or diol-terminated poly(∈-caprolactone) (PCDT) segments are described. The influence of the chemical structure and the length of PEG and PCDT on thermal stability, degree of crystallinity and glass transition temperature (T g ) is discussed. Finally, an evaluation of the hydrolytic behavior in conditions mimicking the physiological environment is reported.

Pharmacokinetic results on naproxen prodrugs based on poly(ethyleneglycol)s

Five prodrugs of S(+)-2-(6-methoxy-2-naphthyl)propionic acid (naproxen), in which the drug was bound by ester linkages to diethyleneglycol (I), triethyleneglycol (II), octanediol (III), butyl-triethyleneglycol (IV), and butyl-tetraethyleneglycol (V), respectively, were prepared and tested for their pharmacokinetic properties after oral administration. It was found that bioavailabilities decreased in the order, and in all cases were lower than that of the free drug.

Synthesis and pharmacokinetic behaviour of ester derivatives of 4-isobutylphenyl-2-propionic acid (Ibuprofen) with end-hydroxylated poly(N-vinyl pyrrolidinone) and poly(N-acryloyl morpholine) oligomers

Four derivatives of 4-isobutylphenyl-2-propionic acid (Ibuprofen), in which the drug was bound by ester linkages to poly(ethylene glycols) (PEG 2000-I), monomethoxy poly(ethylene glycols) (PEG 1900-I), poly(N-vinyl pyrrolidinone) (PVP-I) and poly(N-acryloyl morpholine) (PACM-I), all having approximatively the same number average molecular weight (Mn congruent equal to 2000), were prepared and tested for their pharmacokinetic properties after oral administration. It was found that the two end-hydroxylated amphiphilic oligomers of polyvinylic structure, PACM and PVP, whose physico-chemical properties are comparable to those of PEGs especially as regards solvent affinity, have in principle a similar potential as promoieties for preparing oligomeric prodrugs.