No abstract

New optically active polyesters derived from amino acids by replacement of the backbone amino groups for hydroxyl residues are presented. The polyesters described are the following: poly(L)HOAsp-(COOH)-OH, poly(L)HOGlu(COOH)-OH, poly(L)HOSer(OH)-OH, poly(L)HOThr(OH)-OH, poly-(L)HOLys(OH)-OH, and poly(HOAa(X)(OH)-co-LA) and some other copolymers of R-hydroxy acids. The polymers were prepared via (a) direct condensation in bulk employing several catalysts as PTSA, boric acid, Mukaiyama's reagent, stannous chloride dihydrate, (b) acyl halide activation, and (c) microwaveassisted polymerization. The obtained polymers reached a molecular weight between 1000 and 4000. The highest molecular weight attained employing polycondensation methods in solution, was either by utilizing polyacid, or metal catalyst (boric acid and stannous chloride respectively). Applying oxalyl chloride for chain extension also showed to be an efficient method. On the other hand, the microwave-assisted polymerization exhibited significant advantages and polymerization could be implemented with lack of solvent (neat). The polymers were characterized by several methods (GPC, CD, DSC, solubility), and tested for their degradability and biocompatibility to cell growth. Most of the polymers displayed a linear correlation between their calculated log P values and their experimental contact angles parameters. Transition glass temperatures (T g ) of copolymers with various compositions of LA were correlated to either Gordon Taylor equation or to a three parameters modified Kwei equation. The circular dichroism spectra (CD) of several homo and copolymers were measured. In general, CD curves of the homopolymers of HOSer, HOGlu, HOThr, HOAsp, and HOLys(OH) revealed a significant ester maxima approximately at 205-220 nm while the copolymers of HOSer with HOPhe displayed an additional cotton effect band at 200.6-201.5 nm. This is accounted for polymer rotational isomers and not to a different ππ* transition at lower wavelength.

Biodegradable polyesters derived from hydrophobic amino acids are synthesized by various techniques, resulting in a wide range of molecular weights. The polymers are prepared via a) direct condensation with p-toluenesulfonic acid (PTSA) as catalyst, b) ring-opening polymerization (ROP) of O-carboxyanhydrides, and c) ROP of cyclic dilactones. The polymers obtained by the first method reach a molecular weight ranging from 1000 to 3000 Da, whereas those formed by the second and third method yield extended molecular weights of 15000-30000 Da. The purity of the monomers as well as their steric bulkiness are key factors affecting the polymerizability of cyclic monomers by ROP. Other parameters such as spatial ring alignment and proximity organization may also play a role.

New polymers were synthesized from α-hydroxy acids derived from the natural amino acids Ile, Leu, Phe, and Val, combined with lactic acid, glycolic acid and 6-hydroxyhexanoic acid by direct condensation. The toxicity was determined and the degradation process of these polyesters was investigated under physiological conditions by analyzing the composition of the degraded polymers and the oligomers cleaved in the buffer medium. The polymers were found to be non toxic to two cell lines. Polymers displayed a biphasic degradation behavior. In most cases, a linear relationship was found between the weight loss constant and the hydrophobicity of the polymers, Log P. Regarding the second stage of weight loss, it is apparent that polymers derived from α-hydroxy(L)isoleucine ((L)HOIle) and α-hydroxy(L)Valine ((L)HOVal) degraded much faster than those derived from α-hydroxy(L)leucine ((L)HOLeu) and α-hydroxy(L)phenylalanine ((L)HOPhe), probably due to different spatial orientation of the side chains. Copolymers of 6-hydroxyhexanoic acid displayed slow degradation rates as expected, whereas the degradation profile of copolymers of lactic acid was similar to the other homopolymers. These new polyesters may serve as potential biocompatible materials for medical applications.

One of the challenges in regenerative medicine is the development of novel biodegradable materials to build scaffolds that will support multiple cell types for tissue engineering. Here we describe the preparation, characterization, and cytocompatibility of homo- and hetero-polyesters of α-hydroxy amino acid derivatives with or without lactic acid conjugation. The polymers were prepared by a direct condensation method and characterized using gel permeation chromatography, (1)H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, optical activity, and solubility. The surface charge of the polymers was evaluated using zeta potential measurements. The polymers were coated onto glass cover slips followed by characterization using nano-surface profiler, thin film reflectometry, and atomic force microscopy (AFM). Their interaction with endothelial and neuronal cells was assessed using adhesion, proliferation, and differentiation assays. Of the characterized polymers, Poly-HOVal-LA, but not Poly-(D)HOPhe, significantly augmented nerve growth factor (NGF)-induced neuronal differentiation of the PC12 pheochromcytoma cells. In contrast, Poly-HOLeu increased by 20% the adhesion of endothelial cells, but did not affect PC12 cell differentiation. NGF-induced Erk1/2 phosphorylation in PC12 cells grown on the different polymers was similar to the effect observed for cells cultured on collagen type I. While no significant association could be established between charge and the differentiative/proliferative properties of the polymers, AFM analysis indicated augmentation of NGF-induced neuronal differentiation on smooth polymer surfaces. We conclude that overall selective cytocompatibility and bioactivity might render α-hydroxy amino acid polymers useful as extracellular matrix-mimicking materials for tissue engineering.