Recent results on functional polymers and macromonomers of interest as biomaterials or for biomaterial modification

Trotta

et al. 1999

Macromol. Chem. Phys.

SUMMARY: Polyamidoamine polymers were prepared by hydrogen-transfer polyaddition of 2-methylpiperazine to 2,29-bis(acrylamido)acetic acid sodium salt to yield PAA-1, polyaddition of amino-b-cyclodextrin and 2-methylpiperazine to 2,29-bis(acrylamido)acetic acid to give PAA-2 and polyaddition of the same amino-bcyclodextrin and 2-methylpiperazine to 1,4-bis(acryloyl)piperazine to produce PAA-3. These polymers were reacted with cisplatin to give products containing between 8 -70 wt.-% platinum. The amount of platinum released from the conjugates during incubation at pH 5.5 and pH 7.4 varied between 0 -20%/72 h. PAA-3-Pt showed pH-dependent platinum release. The PAA-platinates were generally less toxic towards lung tumour cell lines in vitro. The IC 50 for cisplatin being 2 -5 lg/mL and for the PAA-platinates 1 -130 lg/mL, this was only to be expected due to their very different cellular pharmacokinetics. In vivo experiments showed that the PAA-1-Pt and PAA-2-Pt were equi-active compared with cisplatin against an i.p. L1210 leukaemia model, confirming their ability to liberate biologically active platinum species. Whereas PAA-1-Pt was significantly less toxic than cisplatin, PAA-2-Pt did show toxicity on repeated dosing, suggesting further investigations are needed to establish the biocompatibility of PAAs containing pendant b-cyclodextrin. PAA-1-Pt is suitable for further in vivo preclinical study in a range of solid tumour models.

Section: Introductionmentioning

confidence: 99%

Synthesis, characterisation and antitumour activity of platinum(II) complexes of novel functionalised poly(amido amine)s

Trotta

et al. 1999

Macromol. Chem. Phys.

“…[14] These PAAs are pH-dependent membrane responsive and have been examined as anticancer drug carriers and endosomolytic vectors for gene and toxin delivery. [12][13][14][15][16] Recently, 'smart' PAAs that bear disulfide linkages regularly arranged along the backbone, and are therefore amenable to both hydrolytic and reductive degradation, have been reported. [17][18][19] Based on this premise, we describe here a synthetic route to novel linear PAAs that bear pendant 2-ethenyldithiopyridine moieties (PAA-SSPy), which involves the disulfide-disulfide exchange reaction of cystamine crosslinked PAAs with 2,2 0 -dithiodipyridine.…”

Section: Introductionmentioning

confidence: 99%

“…Primary bis-amines usually lead to cross-linked PAAs. [9][10][11][12] PAAs are normally degradable in aqueous media [13] and many of them are only moderately toxic in spite of their polycationic nature. [12,14] Amphoteric PAAs that carry pendant carboxy groups are approximately as biocompatible as dextran, and when injected in animals they are endowed with 'stealth-like' properties and passively concentrate in solid tumors by the EPR (enhanced permeation and retention) effect.…”

Section: Introductionmentioning

confidence: 99%

Poly(amidoamine)s with 2‐Dithiopyridine Side Substituents as Intermediates to Peptide–Polymer Conjugates

Macromol. Rapid Commun.

Suardi

et al. 2007

Cystamine, when employed as a cross‐linking agent, leads to poly(amidoamine) networks, which on reaction with 2,2′‐dithiodipyridine turn into linear poly(amidoamine)s with side dithiopyridyl groups that easily undergo exchange reactions with reduced L‐glutathione, a model thiol‐containing biologically active peptide. The resultant products represent the first examples of soluble poly(amidoamine)–peptide conjugates in which the peptide moieties are linked to the polymer chain by SS bonds stable in blood, but cleavable inside cells.magnified image

“…They are highly hydrophilic and usually degrade in aqueous media at a rate depending on their structure. [20] Moreover, many of them are almost non-toxic, in spite of their polycationic nature. Their toxicity was found in a number of tests to be constantly lower by two or three orders of magnitude than that of poly-L-lysine.…”

Section: Introductionmentioning

confidence: 99%

Novel Poly(amido‐amine)‐Based Hydrogels as Scaffolds for Tissue Engineering

Bianchi

Macromolecular Bioscience

et al. 2005

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.