Biomedical subjects

S Brocchini

Publications and source records attributed to S Brocchini.

7 recordsLinked to original sources

PubMed2005

Calorimetric study of bovine serum albumin dilution and adsorption onto polystyrene particles.

Titration calorimetry was used to investigate the interaction between a model antigen, bovine serum albumin (BSA), and a model particulate carrier, polystyrene (PS). The binding enthalpy was much higher than reported in the literature for a similar system and did not display a sigmoidal binding curve. These experiments may have accessed low coverage surface sites due to the irreversible nature of protein binding and stepwise titration. An important correction is the heat of dilution of the protein solution. Two regimes were observed: at low concentrations of BSA (below ca. 0.3% (w/v)) an exothermic dilution enthalpy of ca. -100 mJ mg-1 was determined, whereas at higher concentrations of BSA values of ca. -20 mJ mg-1 were obtained. Solution rheological data also showed a change at 0.3% (w/v) BSA, so we hypothesise that the fraction of the BSA as monomers, dimers and polymers in solution changes at approximately 0.3% (w/v).

Adsorption↗

PubMed2001

Combinatorial chemistry and biomedical polymer development.

Polymers are ubiquitous components of products manufactured for medical and pharmaceutical applications. Widely used commodity polymers were the first polymers to be utilised in biomedical applications. These polymers were not developed with biocompatibility established at the onset and many speciality polymers have been developed in recent years to begin to meet the multifaceted demands for medical development, the optimisation of structure-property correlations and ultimately, clinical use. In the broader area of materials research, combinatorial or high throughput strategies used for drug development are recognised to have potential for discovery and process development. Much of the application of combinatorial chemistry in drugs research has been dependent on the use of polymeric reagents, substrates and supports. The chemistry of the reactions on polymers in solid and liquid phases have also played a major role in combinatorial drugs research. There is considerable interest in combinatorial materials research and this review outlines how this research may be applied for biomedical polymer development.

Animals↗

PubMed2001

New strategies for polymer development in pharmaceutical science--a short review.

We are developing synthetic polymers for pharmaceutical and medical applications. These applications can be broadly grouped on how the polymer will be utilized e.g. material, excipient or molecule. Our focus is to develop polymers with more defined structures that are based on biological, physicochemical and/or materials criteria. Strategies are being developed to more efficiently optimize structure-property correlations during preclinical development. We describe two examples of our research on pharmaceutical polymer development: narrow molecular weight distribution (MWD) homopolymeric precursors which can be functionalized to give families of narrow MWD homo- and co-polymers, and hydrolytically degradable polymers.

Drug Industry↗

PubMed2000

Characterization of combinatorially designed polyarylates by time-of-flight secondary ion mass spectrometry.

A series of 16 polyarylates, with well-controlled and systematically varying chemistry, has been characterized by time-of-flight secondary ion mass spectrometry (TOF-SIMS). The polymers are structurally identical except for the incremental additions of C2H4 units to the backbone and sidechain. From the spectra, peaks characteristic of all polyarylates are identified. Furthermore, evaluation of the spectra and identification of unique signals allow classification of the polyarylates according to sidechain and backbone chemistry.

Combinatorial Chemistry Techniques↗

PubMed1998

Structure-property correlations in a combinatorial library of degradable biomaterials.

A combinatorial library of degradable polyarylates was prepared. These polymers are A-B-type copolymers consisting of an alternating sequence of a diphenol and a diacid. The library was prepared by copolymerizing, in all possible combinations, 14 different tyrosine-derived diphenols and eight different aliphatic diacids, resulting in 8 x 14 = 112 distinct polymers. This approach (a) increases the number of available polymeric candidate materials for medical applications, and (b) facilitates the identification of correlations between polymer structure and glass transition temperature, air-water contact angle, mechanical properties, and fibroblast proliferation. The pendent chain and backbone structures were systematically varied by (a) simple homologative variations in the number of methylene groups, (b) substitution of oxygen for methylene groups, and (c) introduction of branched and aromatic structures. The polymers contained within the library exhibited incremental variations in Tg (from 2 degrees C to 91 degrees C) and air-water contact angle (from 64 degrees to 101 degrees ). Fibroblast proliferation (in vitro, serum-containing media) ranged from approximating that measured on tissue culture polystyrene to complete absence of proliferation. Generally, decreased proliferation correlated linearly with increased surface hydrophobicity, except in those polymers derived from oxygen-containing diacids in their backbone which were uniformly good growth substrates even if their surfaces were very hydrophobic. In a selected subgroup of polymers, tensile strength of thin solvent cast films ranged from about 6 to 45 MPa, while Young's modulus (stiffness) ranged from about 0.3 to 1.7 GPa. Combinatorial biomaterial libraries such as these tyrosine-derived polyarylates permit the systematic study of material-dependent biological responses and provide the medical device designer with the option to choose a suitable material from a library of related polymers that encompasses a broad range of properties.

Animals↗

PubMed1998

The study of water uptake in degradable polymers by thermally stimulated depolarization currents.

Poly(DTH succinate) is a new, degradable polymer with potential applications as a medical implant material. This polymer can be classified as an alternating copolymer of succinic acid and desaminotyrosyl-tyrosine hexyl ester (DTH), a diphenolic monomer derived from the natural amino acid L-tyrosine. In this study, the effects of water uptake (hydration) on the secondary relaxations of poly(DTH succinate) were investigated using the technique of thermally stimulated depolarization currents (TDSC). Four relaxation peaks were precisely characterized by means of Gaussian activation energy distributions. Drying and rehydration treatments show that only small amounts of water, at most 0.5% (w/w), are necessary to hydrate two of the four polar moieties in poly(DTH succinate): the pendent chain ester carbonyls and the amide carbonyls in the polymer backbone. Water appeared to be more tightly bound to the amide carbonyl group and more loosely bound to the ester carbonyl group in the pendent chain. Even at a high state of hydration (1.2% w/w), TDSC indicated that no water was associated with the phenyl ester bond in the polymer backbone. This finding may explain the unexpectedly high stability of this polymer toward hydrolysis under physiological conditions. Polymer packing was also affected by hydration. In an intermediate hydration state (water content: 0.5% w/w) polymer packing was less dense than in the wet state (water content: 1.2% w/w). This study represents the first application of the TDSC technique to the study of hydration in a degradable biomedical polymer. The results obtained indicate that the TDSC technique may be useful to assist in the understanding of the mechanisms of hydration and subsequent hydrolytic degradation in degradable biomaterials.

Biocompatible Materials↗

PubMedDate not supplied

N-(2-hydroxypropyl)methacrylamide copolymer-6-(3-aminopropyl)-ellipticine conjugates. Synthesis, in vitro, and preliminary in vivo evaluation.

Ellipticine derivatives have potential as anticancer drugs. Their clinical use has been limited, however, by poor solubility and host toxicity. As N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anticancer conjugates are showing promise in early clinical trials, a series of novel HPMA copolymer conjugates have been prepared containing the 6-(3-aminopropyl)-ellipticine derivative (APE, NSC176328). Drug was linked to the polymer via GFLG or GG peptide side chains. To optimize biological behavior, HPMA copolymer-GFLG-APE conjugates with different drug loading (total APE: 2.3-7% w/w; free APE: <0.1% w/w) were synthesized. Conjugation of APE to HPMA copolymers considerably increased its aqueous solubility (>10-fold). HPMA copolymer-GG-APE did not liberate drug in the presence of isolated lysosomal enzymes (tritosomes), but HPMA copolymer-GFLG-APE released APE to a maximum of 60% after 5 h. The rate of drug release was influenced by drug loading; lower loading led to greater release. Whereas free APE (35 microg/mL) caused significant hemolysis (50% after 1 h), HPMA copolymer-APE conjugates were not hemolytic up to 300 microg/mL (APE-equiv). As would be expected from its cellular pharmacokinetics, HPMA copolymer-GFLG-APE was >75 times less cytotoxic than free drug (IC(50) approximately 0.4 microg/mL) against B16F10 melanoma in vitro. However, in vivo when tested in mice bearing s.c. B16F10 melanoma, HPMA copolymer-GFLG-APE (1-10 mg/kg single dose, APE-equiv) given i.p. was somewhat more active (highest T/C value of 143%) than free APE (1 mg/kg) (T/C =127%). HPMA copolymer-APE conjugates warrant further evaluation as potential anticancer agents.

Acrylamides↗