In vitro ageing and degradation of PEG-PLA diblock copolymer-based nanoparticles

Diblock copolymers composed of poly(oxy-ethylene) (POE) and poly(dl-lactic acid) segments were synthesized by anionic polymerization of d,l-lactide using the oxyanion formed by reaction of the monohydroxyl monomethoxy-poly(ethylene glycol) on sodium hydride. For comparison, a similar copolymer was prepared by using tin octoate to catalyze the lactide polymerization. The copolymers were used to make nanoparticles, which were stored at 4 °C. After a few months under these storage conditions, a dramatic decrease of the poly(ethylene glycol) content was observed, however, the mean diameter of the nanoparticles was not affected. The degradation of the nanoparticles was investigated in vitro under conditions selected to mimic physiological conditions. Changes of characteristics were monitored by ¹H NMR, SEC, DLLS and CZE on nanoparticles and/or on the degradation by-products dissolved in the ageing medium. According to their nanometric dimensions, the microparticles degraded very slowly and there was no difference in behaviour between the sodium hydride and the stannous octoate-derived copolymers.     

Salt effects on macrophase separations in non‐stoichiometric mixtures of oppositely charged macromolecules: Theory and experiment

In the field of biological applications, polyelectrolyte complexes are proposed to encapsulate bioactive compounds, to deliver drugs, and also to transfect genes into cells under the name of polyplexes. Complex formation is obtained by addition of a polycation solution into a polyanion solution or vice‐versa. This work proposes a theoretical approach to describe complex formation in the case of non‐stoichiometric mixtures of oppositely charged macroions having different degrees of ionization and different degrees of polymerization under different salt conditions. In a second part, comparison was made with experimental data collected when a weak polybase, namely poly(l ‐lysine) under its bromide form was added stepwise to solutions of various polyanions under their sodium salt form, namely poly(l ‐lysine citramide imide), poly(l ‐lysine citramide), and poly(β‐malic acid), the latter lacking hydroxyl groups attached to the main chain. The stability of stroichiometric complexes made of poly(l ‐lysine) and poly(l ‐lysine citramide) having different molecular masses is discussed. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1717–1730     

Present and Future of PLA Polymers

Abstract

Lactic acid-based aliphatic polyesters (PLAs) are well known biocompatible bioresorbable polymers which are being increasingly used as biomaterials for temporary therapeutic applications. Because of their sensitivity to water and the formation of degradation by-products which can be easily metabolized by microorganisms, this type of polymers also has potential to replace commodity polymers in packagings or as mulch films. From an overview of synthesis routes, structural characteristics, and performances, an attempt is made to evaluate the future of PLA polymers insofar as industrial development is concerned.     

Benzyl esters of optically active malic acid stereocopolymers as obtained by ring-opening polymerization of (R)-(+) and (S)-(-)-benzyl malolactonates

(R)-(+) and (S)-(-)-benzyl malolactonates were copolymerized anionically by using triethylamine and aluminum porphyrin as initiators. Configurational composition of resulting optically active poly(benzyl β-malate) stereocopolymers depends on the enantiomeric purity in the monomer feed. Stereochemistry during the multistep synthesis starting from aspartic acid enantiomers used as precursors is discussed. It is shown that natural L(+)-aspartic acid yields (-)-poly(benzyl β-malate) which degrades to L(-)-malic acid in alkaline aqueous medium. Configurational structures were investigated by ¹³C NMR (75.47 MHz) and splittings of stereosensitive resonances are discussed in terms of stereosequence distributions. Results show that stereocopolymerization proceeds through random addition of chiral repeating units according to Bernoullian statistics. In order to exemplify the effect of enantiomeric composition on physical properties, thermal characteristics have been investigated by DSC for the whole series of stereocopolymers. Samples with more than 70% (S) or (R)-units are semicrystalline. Melting temperature and crystallinity increase with stereoregularity.     

Optically active alternating copolymers of maleic anhydride and alkylvinylethers

Maleic anhydride (MAn) was copolymerized in benzene solution at 60° using AIBN with some optically active alkylvinylethers (RVE) having an asymmetric carbon atom at the α, β, γ or δ position with respect to the oxygen atom [R = (S)-1-methylpropyl, (R)-1-methylbutyl, (S)-2-methylbutyl, (S)-3-methylpentyl, (S)-4-methylhexyl, (S)-1-methylheptyl and (S)-3,7-dimethyloctyl]. Chemical compositions and solubilities of the polymeric products as well as optical rotation properties and spectroscopic measurements (i.r. and NMR) confirmed the formation of copolymers with a predominantly alternating structure. Two Cotton effects of low but definite intensity attributable to $\text{n → π}{}^1$ electronic transitions of carbonyl groups of anhydride moieties were observed between 200 and 250 nm. Failure to achieve complete cleavage of chiral side chains does not enable us to attribute the induced optical activity of anhydride moieties either to the asymmetric carbon atom present in the side chain or to the tertiary chiral centres present in the main chain or both.     

Methylated and pegylated PLA–PCL–PLA block copolymers via the chemical modification of di‐hydroxy PCL combined with the ring opening polymerization of lactide

Methylated and pegylated poly(lactide)‐block‐poly(ε‐caprolactone)‐block‐poly(lactide) copolymers, PLA–P(CL‐co‐CLCH₃)–PLA and PLA–P(CL‐co‐CLPEG)–PLA, were prepared in three steps: combining the formation of carbanion‐bearing dihydroxylated‐PCL, the coupling of iodomethane or bromoacetylated α‐hydroxyl‐ω‐methoxy‐poly(ethylene glycol) onto the carbanionic PCL, and finally the ring opening polymerization of DL ‐lactide initiated by the preformed grafted diOH‐PCL copolymers. The resulting block copolymers exhibited lower crystallinity, melting temperature, and hydrophobicity with respect to the original PCL. Degradation of the grafted copolymers was investigated in the presence of Pseudomonas cepacia lipase and compared with that of the triblock copolymer precursor. It is shown that the presence of the grafted substituents affected the enzymatic degradation of PCL segments. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4196–4205, 2005     

Polymerisation von Oxiranylalkylaminen und Thiiranylalkylaminen, die sich von optisch aktiven und racemischen sekund?ren Aminen ableiten

Ohne Zusammenfassung     

Polymeres optiquement actifs—X. Mise en evidence d'une reaction secondaire au cours de la polycondensation en milieu acide du formaldehyde et de la n-tosyl l-tyrosine. Influence sur l'activite optique

The variation of the optical rotatory dispersion (ORD) of the acid-catalysed phenol-formaldehyde type polycondensate of N-tosyl l-tyrosine (I) with its degree of ionization can only be explained by a secondary reaction which modifies the monomeric unit. This reaction is initially explored using a non-polycondensable model of (I): N-tosyl l-phenylalanine (II). The formaldehyde reacts with the secondary sulphonamide function of (II) to give the tosyl derivative of 3-carboxy 1,2,3,4 tetrahydro isoquinoline (III). By comparing the ORD of (I), (II), (III) and those of polymers prepared under different conditions, it is shown that during the polycondensation of (I) in acidic medium, the formaldehyde reacts also with some of the sulphonamide functions, thus giving rise to a copolymer instead of a homopolymer. The proportions of the two units are assessed using i.r. spectra.     

The pharmacophore kernel for virtual screening with support vector machines

We introduce a family of positive definite kernels specifically optimized for the manipulation of 3D structures of molecules with kernel methods. The kernels are based on the comparison of the three-point pharmacophores present in the 3D structures of molecules, a set of molecular features known to be particularly relevant for virtual screening applications. We present a computationally demanding exact implementation of these kernels, as well as fast approximations related to the classical fingerprint-based approaches. Experimental results suggest that this new approach is competitive with state-of-the-art algorithms based on the 2D structure of molecules for the detection of inhibitors of several drug targets.