Well–defined polyesters for applications in life science

This work of thesis describes the preparation of polyester-based materials of interest for applications in biomedical field. Starting from the polymerization design, varied catalytic systems and monomers were selected to access novel materials. Representing a healthier alternative to heavy metal complexes often employed in industry, strontium isopropoxide was employed for the first time as a catalyst for the polymerization of L–lactide and a selection of lactones, proving a high activity and an excellent molar mass already at room temperature. The selection of suitable catalysts was furthermore complemented with the development of copolymers with the same Hydrophilic Hydrophobic Balance (HHB) of poly(lactic acid) or poly(caprolactone). As a result, new polyesters with similar molar mass featuring a controlled variation of thermal properties were prepared and used for the preparation of stable nanoparticle suspensions with similar size. This study enabled to prove: (a) The direct relationship between the bulk thermal properties and the nanoparticle stiffness; (b) the role of synthetic design for both the controlled variation of polyesters properties and for the preparation of tailor-made PLA stereocomplexes; and (c) the experimental proof on how polyester design allow the preparation of nanoparticles with constant HHB

Strontium isopropoxide: a highly active catalyst for the ring‐opening polymerization of lactide and various lactones

Abstract Commercially available strontium isopropoxide represents a suitable catalyst/initiator for the ring‐opening polymerization (ROP) of lactide (LA), ε−caprolactone, δ−valerolactone, δ−caprolactone, and δ−decalactone. Well‐defined polyesters are accessible via the solution polymerization of lactide in toluene with a [LA]:[Sr] ratio of 100:1 at room temperature with or without the addition of dodecanol as coinitiator. Kinetic studies and detailed analysis by means of matrix‐assisted laser desorption ionization mass spectrometry reveal pseudo‐first‐order kinetics of the ROP as well as excellent endgroup fidelity of the polylactide (PLA) with isopropyl and dodecyl α‐endgroups. Both isopropanolate moieties as well as the coinitiator each initiate PLA chains, enabling the synthesis of PLA with tailored molar mass. The polymerization of ε−caprolactone and δ−valerolactone confirms the high catalyst activity, which causes quantitative monomer conversion after 1 min polymerization time but broad molar mass distributions. In contrast, the catalyst is well suited for the ROP of the less reactive δ−caprolactone and δ−decalactone. Although kinetic studies reveal initially bimodal molar mass distributions, polyesters with dispersity values Ð < 1.2 and unimodal molar mass distributions can be obtained at moderate to high monomer conversions

Strontium Isopropoxide: A Highly Active Catalyst for the Ring‐Opening Polymerization of Lactide and Various Lactones

Abstract Commercially available strontium isopropoxide represents a suitable catalyst/initiator for the ring‐opening polymerization (ROP) of lactide (LA), ε−caprolactone, δ−valerolactone, δ−caprolactone, and δ−decalactone. Well‐defined polyesters are accessible via the solution polymerization of lactide in toluene with a [LA]:[Sr] ratio of 100:1 at room temperature with or without the addition of dodecanol as coinitiator. Kinetic studies and detailed analysis by means of matrix‐assisted laser desorption ionization mass spectrometry reveal pseudo‐first‐order kinetics of the ROP as well as excellent endgroup fidelity of the polylactide (PLA) with isopropyl and dodecyl α‐endgroups. Both isopropanolate moieties as well as the coinitiator each initiate PLA chains, enabling the synthesis of PLA with tailored molar mass. The polymerization of ε−caprolactone and δ−valerolactone confirms the high catalyst activity, which causes quantitative monomer conversion after 1 min polymerization time but broad molar mass distributions. In contrast, the catalyst is well suited for the ROP of the less reactive δ−caprolactone and δ−decalactone. Although kinetic studies reveal initially bimodal molar mass distributions, polyesters with dispersity values Ð < 1.2 and unimodal molar mass distributions can be obtained at moderate to high monomer conversions

Nitrile hydration to amide in water: Palladium-based nanoparticles vs molecular catalyst

The catalytic performance of small Pd-nanoparticles (NPs) (2.0 nm), partially covered by chemisorbed oxygen atoms, and of Pd-acetate, both stabilized by 2,2′-bipyridine-end functionalized poly(ethyleneglycol) monomethylether was compared in the selective hydration of nitriles to amide in water under mild reaction conditions (353 K). Regardless of the nitrile substrate employed, the Pd-NP-based catalyst showed much higher normalized TON-values (i.e. refereeing to the amount of surface Pd atoms) compared to the Pd(II) macrocomplex, as far as the first catalytic run was considered. Deactivation of the Pd-NP-based catalyst was significant due to the formation of a hydroxide-water layer on the NPs’ surfac

Effect of Crystallinity on the Properties of Polycaprolactone Nanoparticles Containing the Dual FLAP/mPEGS-1 Inhibitor BRP-187

Seven polycaprolactones (PCL) with constant hydrophobicity but a varying degree of crystallinity prepared from the constitutional isomers ε-caprolactone (εCL) and δ-caprolactone (δCL) were utilized to formulate nanoparticles (NPs). The aim was to investigate the effect of the crystallinity of the bulk polymers on the enzymatic degradation of the particles. Furthermore, their efficiency to encapsulate the hydrophobic anti-inflammatory drug BRP-187 and the final in vitro performance of the resulting NPs were evaluated. Initially, high-throughput nanoprecipitation was employed for the εCL and δCL homopolymers to screen and establish important formulation parameters (organic solvent, polymer and surfactant concentration). Next, BRP-187-loaded PCL nanoparticles were prepared by batch nanoprecipitation and characterized using dynamic light scattering, scanning electron microscopy and UV-Vis spectroscopy to determine and to compare particle size, polydispersity, zeta potential, drug loading as well as the apparent enzymatic degradation as a function of the copolymer composition. Ultimately, NPs were examined for their potency in vitro in human polymorphonuclear leukocytes to inhibit the BRP-187 target 5-lipoxygenase-activating protein (FLAP). It was evident by Tukey’s multi-comparison test that the degree of crystallinity of copolymers directly influenced their apparent enzymatic degradation and consequently their efficiency to inhibit the drug target

Maintaining the Hydrophilic–Hydrophobic Balance of Polyesters with Adjustable Crystallinity for Tailor-Made Nanoparticles

To explore the relationship between thermal properties of a polymer and the biological performance of the resulting nanoparticle, all other parameters, including the hydrophobicity, should be kept constant. For this purpose, a gradient and a block copolyester were tailor-made via the triazabicyclodecene catalyzed ring-opening copolymerization of δ-valerolactone (δVL) and δ-decalactone (δDL) to match the hydrophobicity of poly­(ε-caprolactone) (PεCL). The degree of crystallinity of the semicrystalline materials was significantly reduced due to the incorporation of amorphous PδDL segments, as confirmed by dynamic scanning calorimetry. Atomic force microscopy revealed short and randomly oriented crystals in the gradient copolymer but longer and parallel aligned crystals for the block copolymer and PεCL. The stiffness of nanoparticles (<i>D</i>_h ≈ 170 nm) prepared from the polyesters correlated to the bulk crystallinity. The set of nanoparticles with constant hydrophobicity and size will facilitate direct access to the influence of the nanoparticle crystallinity on biological processes such as enzymatic degradation, drug release, and cellular uptake