E. Chiellini

New Multicomponent Bioerodible Electrospun Nanofibers for Dual-controlled Drug Release

The objective of this study was to evaluate the bioerodible polymer poly(maleic anhydride-alt-2-methoxyethyl vinyl ether) n-butyl hemiester, for multicomponent drug-loaded nanofibers produced by electrospinning. Diclofenac sodium (DS) and human serum albumin (HSA) were used as conventional drug and biopharmaceutical models. The influence of drug loading was correlated to beads presence, morphology and fibers diameter. When DS and HSA were loaded separately, a uniform distribution within fibers and beads was observed. However, when both components were loaded simultaneously, a heterogeneous distribution of DS was observed with a prominent amount in the cylindrical beads. The in vitro drug release evaluation from these nanomaterials displayed an independent delivery of the two components. These studies support the feasibility of multicomponent, bioerodible polymeric nanofibers preparation loaded with combination of traditional drugs and proteins.

Controlled Release of Herbicides Supported on Polysaccharide Based Hydrogels

Polymeric hydrogels based on polysaccharides, hydroxyethylcellu lose and dextran, were attained by cross-linking with epichlorohydrin. The cross-linked polymer beads were loaded with 2,4-dichlorophenoxyacetic acid by direct esterification in the presence of carbonyldiimidazole. Loads ranging be tween 0.5 and 2.2 mol of 2,4-dichlorophenoxyacetyloyl groups per glucose unit were obtained. The release of 2,4-D herbicide was investigated in buffered aqueous solution at different pH values (4, 7 and 9) and evaluated with respect to different structural parameters, such as nature of the polymer matrices, cross-linking extent and herbicide loading. A fairly slow release, ranging from 10 to 25% after four months, was recorded under neutral and acid conditions, whereas at pH 9 an initial burst in the release profile, reaching almost 90% release of 2,4-D loading, was observed. In the majority of the cases, the release kinetics are reproduced by the combination of two exponential decay processes, that differ by about three orders of magnitude in their absolute rates.

Targeted Administration of Proteic Drugs: I. Preparation of Polymeric Nanoparticles

The formulation of hybrid nanoparticles based on synthetic polymer-protein hybrid matrices for the targeted release of proteic drugs with antiviral activity such as a-interferon was investigated. Human serum albumin, alone, or in combination with myoglobin, and the hemiesters of alternating copolymers of maleic anhydride/alkyl vinyl ethers of oligo(ethylene glycol) were selected as proteic and synthetic components, respectively. Digalactosyl diacyl gycerol, a natural glycolipid selectively recognized by the asialofetuin receptor was used for the active targeting of liver hepatocytes. Nanoparticle suspensions were prepared either by slow solvent evaporation from biphase and triphase emulsions or by controlled coprecipitation. Nanoparticles, 0.1-0.3 gm in diameter, were obtained by the latter method, whereas the former one afforded heterogeneous micro and nanoparticle mixtures. Several techniques were tested to separate the nanoparticle dispersions from the suspending solution. The best results, in terms of a homogeneous distribution of mostly spherical nanoparticles, were obtained by centrifugation in the presence of modified cyclodextrins. After lyophilization of supernatant, the resulting fluffy powder was easily resuspendable in water.

Modelling of beta-cyclodextrin with L-alpha-aminoacids residues

A computational study of host-guest inclusion complexes between β-cyclodextrin (β-CD) and the 20 natural L-α-aminoacids and some selected pentapeptides was carried out and aimed at understanding the nature of the driving forces and mechanism leading to their formation. Relative complexation energies for the complexes with β-CD were calculated in both cases and the solvation Gibbs free energies were also evaluated for the single L-α-aminoacids. The computed results indicate strong possibilities of formation of inclusion complexes between β-CD and single L-α-aminoacids as well as pentapeptides which have hydrophobic side chains. In addition, noteworthy interactions of the side chain of the pentapeptides with the β-CD were also elucidated. A detailed molecular dynamics calculation of one of the representative pentapeptide/β-CD inclusion complex (β-CD/CH3-Ala-Ala- TYR-Ala-Ala-CH3) in aqueous solution has also been carried out. Molecular dynamics calculations support aspects connected with the formation and description of hydrogen bonds and with the role of dispersion forces in the inclusion complex in water.

Azobenzene containing polymers: what is yet viable with aged liquid crystals

A Commentary on the paper ”Photochromic liquid crystalline polymers. Main chain and side chain polymers containing azobenzene mesogens„, by A. S. Angeloni, D. Caretti, C. Carlini, E. Chiellini, G. Galli, A. Altomare, R. Solaro and M. Laus. First published in Liquid Crystals, 4, 513‐527 (1989).

New hydrophilic polyesters and related polymers as bioerodible polymeric matrices

A survey is reported on our activity performed in the last few years on the preparation of new synthetic and semisynthetic polymeric materials endowed with bioerodible-biodegradable characteristics and designed for applications in the practice of controlled release of active principles of pharmaceutical and agrochemical significance. The presentation of the results will be arranged into the following sections: (1) hydroxyl containing polyesters, that comprise polymerization products based on racemic and optically active glyceric acid, or attained by polyaddition reactions among cyclic anhydrides, including also carbon dioxide, with monoglycidyl ethers of reversibly protected polyols. In this class are also presented the related polyhydroxylated systems obtained by selective grafting functional epoxides on cyclodextrins. (2) Bioerodible carboxyl containing polymeric systems as derived from the alternating copolymerization of maleic anhydride with alkyl vinyl ethers followed by partial esterification of maleic anhydride groups. (3) Linear and cross-linked functional polymers of synthetic and semisynthetic origin with hydrogel forming capability. Typical examples of their applications in the release of drugs and phytodrugs are also presented.

New structurally modified cyclodextrins for controlled release of antihypertensive drugs

New β-cyclodextrin derivatives were prepared by grafting glycidyl ethers of alditols having an odd number of hydroxyl groups protected with isopropylidene groups. The modified β-cyclodextrins or commercially available hydroxypropyl-β-cyclodextrin were used to prepare drug conjugates of antihypertensive drugs such as nifedipine, corynanthine and Oxprenolol. Preliminary in vivo experiments indicate an improvement of drug absorption, bioavailability and antihypertensive efficacy.

Removal of viruscide agents by using styrenic resins

Strong and weak anionic polystyrene/divinylbenzene ion exchange resins were investigated both as iodophores and as iodine/iodide ion removal agents in blood disinfection applications. Resin-iodine complexes were prepared, but there was no significant iodine release observed in either distilled water or isotonic saline solution. However, all ion-exchange resin were able to remove almost quantitatively both iodine and iodide ions from water solutions. Cross-linked styrene/divinylbenzene resins are excellent polyaromatic viruscide adsorbents, although their hydrophobicity is responsible for poor wettability in physiologi-cal fluids. Surface modification with hydrophilic reagents appeared a promising strategy to overcome this drawback. A Merrifield-type chloromethylated resin and a highly cross-linked mesoporous resin (Lewatit 1064) with a large surface area and content of unreacted vinyl groups were selected as starting materials. The Merrifield resin was modified by the reaction of the pendant chloromethyl groups with triethyleneglycol, tetraethyleneglycol and â -cyclodextrin. The conversion of Lewatit double bonds into hydrophilic moieties was attempted by the radical grafting of N-vinyl-2-pyrrolidinone (NVP), maleic anhydride (MAn), 2-hydroxyethyl methacrylate, acrylamide (AAm) and different poly(ethyleneglycol) (PEG) methacrylates. The addition of 2-mer-captoethanol (2ME) and epoxidation were also investigated. The modified Merrifield resins demonstrated very low efficiency in acridine viruscide uptake, in spite of the large increase in both wettability and water uptake. On the other hand, all modified Lewatit samples removed rapidly and almost quantitatively the viruscide from aqueous solutions, although only a few samples resulted in being very hydrophilic. In all cases, hydrophilicity and viruscide adsorbing capacity were maintained after heating at 180 degrees C to simulate pyrogen elimination.

Synthesis and Properties of Block Copolymers with Polystyrene and Liquid Crystalline Polyester Blocks

ABSTRACT The synthesis as well as the thermal and dynamic-mechanical properties of a new class of block copolymers, comprised of polystyrene and main-chain liquid crystalline blocks, are reported. The two blocks are incompatible in the solid and melted phases and undergo distinct thermal transitions. The melting and nematic to isotropic transition temperatures of the main-chain block are constant within the whole compositional range. The nematic to isotropic transition enthalpies are directly proportional to the weight of the main-chain liquid crystalline block. A substantial decrease of the crystallization propensity of the main-chain block is observed.

Diclofenac sodium (DS) loaded bioerodible polymer based constructs

Pain is a prevalent problem that can raise morbidity of patients. Pain killer releasing biodegradable materials have been developed by using different techniques and biomaterials. The objective of the current study is to evaluate the use of a new bioerodible polymer for release of diclofenac sodium (DS). 1‐butanol hemiester poly(maleic anhydride‐alt‐2‐methoxyethyl vinyl ether) (PAM14) was prepared in the university of Pisa and selected as polymer of choice for the study. Polymer solutions of 5–10% (in ethanol or in acetic acid) were prepared, half of them containing 2% DS. The solutions were then electrospun to produce nanomats that were subsequently characterized using SEM. Fiber diameter was 160 nm 1 μm. Increasing polymer concentration increased the size of the fibers but reduced the number of beads (with or without DS). In the specimens obtained from acetic acid solution, the addition of DS resulted in a reduction in fiber diameter and an increase in the inter‐bead distance. Corresponding ethanol solu...