TY - GEN A1 - Naolou, Toufik A1 - Rühl, Eckart A1 - Lendlein, Andreas T1 - Nanocarriers BT - Architecture, transport, and topical application of drugs for therapeutic use T2 - European Journal of Pharmaceutics and Biopharmaceutics Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2017.03.004 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 1 EP - 3 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wang, Weiwei A1 - Naolou, Toufik A1 - Ma, Nan A1 - Deng, Zijun A1 - Xu, Xun A1 - Mansfeld, Ulrich A1 - Wischke, Christian A1 - Gossen, Manfred A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M (n) similar to 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells. Y1 - 2017 U6 - https://doi.org/10.1021/acs.biomac.7b01034 SN - 1525-7797 SN - 1526-4602 VL - 18 SP - 3819 EP - 3833 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Naolou, Toufik A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Amides as non-polymerizable catalytic adjuncts enable the ring-opening polymerization of lactide with ferrous acetate under mild conditions JF - Frontiers in Chemistry N2 - Sn-based catalysts are effective in the ring-opening polymerization (ROP) but are toxic. Fe(OAc)(2) used as an alternative catalyst is suitable for the ROP of lactide only at higher temperatures (>170 degrees C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)(2) to polydepsipeptides at 135 degrees C, ester bonds were selectively opened. Here, it was hypothesized that ROP of lactones is possible with Fe(OAc)(2) when amides are present in the reactions mixture as Fe-ligands could increase the solubility and activity of the metal catalytic center. The ROP of lactide in the melt with Fe(OAc)(2) is possible at temperatures as low as 105 degrees C, in the presence of N-ethylacetamide or N-rnethylbenzamide as non-polymerizable catalytic adjuncts (NPCA), with high conversion (up to 99 mol%) and yield (up to 88 mol%). Polydispersities of polylactide decreased with decreasing reaction temperature to <= 1.1. NMR as well as polarimetric studies showed that no racemization occurred at reaction temperatures <= 145 degrees C. A kinetic study demonstrated a living chain-growth mechanism. MALDI analysis revealed that no side reactions (e.g., cyclization) occurred, though transesterification took place. KW - ring-opening polymerization KW - polyester KW - catalyst KW - iron KW - amide ligand Y1 - 2019 U6 - https://doi.org/10.3389/fchem.2019.00346 SN - 2296-2646 VL - 7 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Naolou, Toufik A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Influence of metal softness on the metal-organic catalyzed polymerization of inorpholin-2,5-diones to oligodepsipeptides JF - European polymer journal Y1 - 2016 U6 - https://doi.org/10.1016/j.eurpolymj.2016.10.011 SN - 0014-3057 SN - 1873-1945 VL - 85 SP - 139 EP - 149 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Brunacci, Nadia A1 - Neffe, Axel T. A1 - Wischke, Christian A1 - Naolou, Toufik A1 - Nöchel, Ulrich A1 - Lendlein, Andreas T1 - Oligodepsipeptide (nano)carriers BT - computational design and analysis of enhanced drug loading JF - Journal of controlled release N2 - High drug loads of nanoparticles are essential to efficiently provide a desired dosage in the required timeframe, however, these conditions may not be reached with so far established degradable matrices. Our conceptual approach for increasing the drug load is based on strengthening the affinity between drug and matrix in combination with stabilizing drug-matrix-hybrids through strong intermolecular matrix interactions. Here, a method for designing such complex drug-matrix hybrids is introduced employing computational methods (molecular dynamics and docking) as well as experimental studies (affinity, drug loading and distribution, drug release from films and nanoparticles). As model system, dexamethasone (DXM), relevant for the treatment of inflammatory diseases, in combination with poly[(rac-lactide)-co-glycolide] (PLGA) as standard degradable matrix or oligo[(3-(S)-sec-butyl) morpholine-2,5-dione] diol (OBMD) as matrix with hypothesized stronger interaction with DXM were investigated. Docking studies predicted higher affinity of DXM to OBMD than PLGA and displayed amide bond participation in hydrogen bonding with OBMD. Experimental investigations on films and nanoparticles, i.e. matrices of different shapes and sizes, confirmed this phenomenon as shown e.g. by a similar to 10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of similar to 150 nm prepared by nanoprecipitation in aqueous environment had a drug loading (DL) up to 16 times higher when employing OBMD as matrix compared to PLGA carriers due to enhanced drug retention in the OBMD phase. Importantly, drug relase periods were not altered as the release from films and particles was mainly ruled by the diffusion length as well as matrix degradation rather than the matrix type, which can be assigned to water diffusing into the matrix and breaking up of drug-matrix hydrogen bonds. Overall, the presented design and fabrication scheme showed predictive power and might universally enable the screening of drug/matrix interactions particularly to expand the oligodepsipeptide platform technology, e.g. by varying the depsipeptide side chains, for drug carrier and release systems. KW - Oligodepsipeptide KW - Drug loading KW - Nanoparticles KW - Docking study KW - Molecular interaction design Y1 - 2019 U6 - https://doi.org/10.1016/j.jconrel.2019.03.004 SN - 0168-3659 SN - 1873-4995 VL - 301 SP - 146 EP - 156 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Brunacci, Nadia A1 - Wischke, Christian A1 - Naolou, Toufik A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Influence of surfactants on depsipeptide submicron particle formation JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5-20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of M-n= 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-alpha-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250-400 nm, PVA; 300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. (C) 2016 Elsevier B.V. All rights reserved. KW - Depsipeptide KW - Particle size KW - Surfactants KW - Submicron particles Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.11.011 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 61 EP - 65 PB - Elsevier CY - Amsterdam ER -