14825-82-2Relevant academic research and scientific papers
Dual-responsive star-shaped polypeptides for drug delivery
Wang, Wenlong,Zhang, Liang,Liu, Mengtao,Le, Yuan,Lv, Shanshan,Wang, Jiexin,Chen, Jian-Feng
, p. 6368 - 6377 (2016)
Core cross-linked star-shaped polypeptides based on poly(l-glutamic acid)-poly(l-phenylalanine-co-l-cystine) copolymer have been successfully synthesized and thoroughly characterized. The star polypeptides can self-assemble to form 50 nm micelles in aqueous medium, which respond rapidly to both pH change within the physiologically relevant pH range and a reduction environment mimicking the intracellular space. Water-soluble doxorubicin hydrochloride and hydrophobic resveratrol are loaded into the star polypeptides micelles through electrostatic and hydrophobic interactions respectively. The drug loading content can be controlled by tuning the composition of the star polypeptides. The in vitro release studies indicate dual sensitivity enabled rapid drug release at pH 5.5 and 10 mM dithiothreitol (DTT), mimicking the intracellular environment. Furthermore, the star polypeptides are biocompatible and interact well with cells in vitro. Confocal fluorescence microscopy and flow cytometry assays show these star polypeptides can be quickly internalized and effectively deliver the drugs into HeLa cells to inhibit cell growth.
Synthesis of poly(ethylene glycol)/polypeptide/poly(D, L -lactide) copolymers and their nanoparticles
Lee, Hyunpyo,Park, Jun Beum,Chang, Ji Young
, p. 2859 - 2865 (2011)
Core-shell structured nanoparticles of poly(ethylene glycol) (PEG)/polypeptide/poly(D,L-lactide) (PLA) copolymers were prepared and their properties were investigated. The copolymers had a poly(L-serine) or poly(L-phenylalanine) block as a linker between a hydrophilic PEG and a hydrophobic PLA unit. They formed core-shell structured nanoparticles, where the polypeptide block resided at the interface between a hydrophilic PEG shell and a hydrophobic PLA core. In the synthesis, poly(ethylene glycol)-b-poly(L-serine) (PEG-PSER) was prepared by ring opening polymerization of N-carboxyanhydride of O-(tert-butyl)-L-serine and subsequent removal of tert-butyl groups. Poly(ethylene glycol)-b-poly(L-phenylalanine) (PEG-PPA) was obtained by ring opening polymerization of N-carboxyanhydride of L-phenylalanine. Methoxy-poly(ethylene glycol)-amine with a MW of 5000 was used as an initiator for both polymerizations. The polymerization of D,L-lactide by initiation with PEG-PSER and PEG-PPA produced a comb-like copolymer, poly(ethylene glycol)-b-[poly(L-serine)-g-poly(D,L-lactide)] (PEG-PSER-PLA) and a linear copolymer, poly(ethylene glycol)-b-poly(L-phenylalanine)-b-poly(D,L-lactide) (PEG-PPA-PLA), respectively. The nanoparticles obtained from PEG-PPA-PLA showed a negative zeta potential value of -16.6 mV, while those of PEG-PSER-PLA exhibited a positive value of about 19.3 mV. In pH 7.0 phosphate buffer solution at 36 °C, the nanoparticles of PEG/polypeptide/PLA copolymers showed much better stability than those of a linear PEG-PLA copolymer having a comparable molecular weight.
Investigation of N-carbamoylamino acid nitrosation by {NO + O2 in the solid-gas phase. Effects of NOx speciation and kinetic evidence for a multiple-stage process
Lagrille, Olivier,Taillades, Jacques,Boiteau, Laurent,Commeyras, Auguste
, p. 271 - 284 (2007)
Nitrosation of N-carbamoylamino acids (CAA) by gaseous NO + O2, an interesting synthetic pathway to amino acid N-carboxyanhydrides (NCA), alternative to the phosgene route, was investigated on N-carbamoyl-valine either in acetonitrile suspension or solventless conditions, and compared to the classical nitrosating system NaNO2 + CF3COOH (TFA), the latter being quite less efficient in terms of either rate, stoichiometric demand, or further tractability of the product. The rate and efficiency of the NO + O2 reaction mainly depends on the O2/NO ratio. Evaluation of the contribution of various nitrosating species (N 2O3, N2O4, HNO2) through stoichiometric balance showed the reaction to be effected mostly by N 2O3 for O2/NO ratios below 0.3, and by N 2O4 for O2/NO ratios above 0.4. The relative contribution of (subsequently formed) HNO2 always remains minor. Differential scanning calorimetry (DSC) monitoring of the reaction in the solid phase by either HNO2 (from NaNO2 + TFA), gaseous N 2O4 or gaseous N2O3, provides the associated rate constants (ca. 0.1, 2 and 108 s-1 at 25°C, respectively), showing that N2O3 is by far the most reactive of these nitrosating species. From the DSC measurement, the latent heat of fusion of N2O3, 2.74 kJ ·mol-1 at -105 °C is also obtained for the first time. The kinetics was investigated under solventless conditions at 0°C, by either quenching experiments or less tedious, rough calorimetric techniques. Auto-accelerated, parabolic-shaped kinetics was observed in the first half of the reaction course, together with substantial heat release (temperature increase of ca. 20°C within 1-2 min in a 20-mg sample), followed by pseudo-zero-order kinetics after a sudden, important decrease in apparent rate. This kinetic break is possibly due to the transition between the initial solid-gas system and a solid-liquid-gas system resulting from water formation. Overall rate constants increased with parameters such as the specific surface of the solid, the O 2/NO ratio, or the presence of moisture (or equivalently the hydrophilicity of the involved CAA), however without precise relationship, while the last two parameters may directly correlate to the increasing acidity of the medium. Copyright
Complete surface control of peptide nanospheres with detachable and attachable polymer brush layers
Waku, Tomonori,Matsumoto, Masahiro,Matsusaki, Michiya,Akashi, Mitsuru
, p. 7025 - 7027 (2010)
The surfaces of biodegradable peptide nanospheres with density-controllable poly(ethylene glycol) (PEG) brush layers were amenable to high levels of control, from hydrophilic 'stealth' properties to hydrophobic adsorptive properties depending on the PEG density in response to environmental conditions - 'intelligent' properties that are expected to be useful for novel drug delivery systems.
Biodegradable hybrid polymer micelles for combination drug therapy in ovarian cancer
Desale, Swapnil S.,Cohen, Samuel M.,Zhao, Yi,Kabanov, Alexander V.,Bronich, Tatiana K.
, p. 339 - 348 (2013)
The co-delivery of drug combination at a controlled ratio via the same vehicle to the cancer cells is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and increased therapeutic potency. In an attempt to develop such multidrug vehicle this work focuses on functional biodegradable and biocompatible polypeptide-based polymeric micelles. Triblock copolymers containing the blocks of ethylene glycol, glutamic acid and phenylalanine (PEG-PGlu-PPhe) were successfully synthesized via NCA-based ring-opening copolymerization and their composition was confirmed by 1H NMR. Self-assembly behavior of PEG-PGlu 90-PPhe25 was utilized for the synthesis of hybrid micelles with PPhe hydrophobic core, cross-linked ionic PGlu intermediate shell layer, and PEG corona. Cross-linked (cl) micelles were about 90 nm in diameter (ξ-potential = -20 mV), uniform (narrow size distribution), and exhibited nanogels-like behavior. Degradation of cl-micelles was observed in the presence of proteolytic enzymes (cathepsin B). The resulting cl-micelles can incorporate the combination of drugs with very different physical properties such as cisplatin (15 w/w% loading) and paclitaxel (9 w/w% loading). Binary drug combination in cl-micelles exhibited synergistic cytotoxicity against human ovarian A2780 cancer cells and exerted a superior antitumor activity by comparison to individual drug-loaded micelles or free cisplatin in cancer xenograft model in vivo. Tunable composition and stability of these hybrid biodegradable micelles provide platform for drug combination delivery in a broad range of cancers.
Supramolecular hydrogels with reverse thermal gelation properties from (Oligo)tyrosine containing block copolymers
Huang, Jin,Hastings, Conn L.,Duffy, Garry P.,Kelly, Helena M.,Raeburn, Jaclyn,Adams, Dave J.,Heise, Andreas
, p. 200 - 206 (2013)
Novel block copolymers comprising poly(ethylene glycol) (PEG) and an oligo(tyrosine) block were synthesized in different compositions by N-carboxyanhydride (NCA) polymerization. It was shown that PEG2000-Tyr 6 undergoes thermoresponsive hydrogelation at a low concentration range of 0.25-3.0 wt % within a temperature range of 25-50 C. Cryogenic transmission electron microscopy (Cryo-TEM) revealed a continuous network of fibers throughout the hydrogel sample, even at concentrations as low as 0.25 wt %. Circular dichroism (CD) results suggest that better packing of the β-sheet tyrosine block at increasing temperature induces the reverse thermogelation. A preliminary assessment of the potential of the hydrogel for in vitro application confirmed the hydrogel is not cytotoxic, is biodegradable, and produced a sustained release of a small-molecule drug.
Synthesis of novel copolymer: Poly(p-dioxanone-co-l-phenylalanine)
Wang, Bing,Ma, Chi,Xiong, Zuo-Chun,Xiong, Cheng-Dong,Zhou, Quan-Hua,Chen, Dong-Liang
, p. 392 - 396 (2013)
In order to expand the application of poly(p-dioxanone) or PPDO in biomedical area, a series of novel copolymers were synthesized successfully by one-step, melted copolymerization of p-dioxanone (PDO) and l-phenylalanine N-carboxyanhydride (l-Phe-NCA) monomers. With the in-feed molar ratio of l-Phe-NCA/PDO equal to 1/20, the conversions of the two kinds of monomers were calculated from 1H NMR. The average molecular weight and polydispersity of the copolymer increase with the increasing reaction time and catalyst concentration. However, the conversions of the two kinds of monomers did not change with the reaction conditions. A three-step mechanism is presented and proved by high resolution 1H NMR and IR spectrums.
A Facile Synthesis of N-Carboxyanhydrides and Poly(α-amino acid) Using Di-tert-butyltricarbonate
Nagai, Atsushi,Sato, Daisuke,Ishikawa, Junichi,Ochiai, Bungo,Kudo, Hiroto,Endo, Takeshi
, p. 2332 - 2334 (2004)
A facile synthesis of N-carboxyanhydrides and poly(α-amino acid) using di-tert-butyltricarbonate (DBTC) is discussed. A one-pot synthesis of poly(amino acid) from an amino acid and DBTC as a dehydrating agent is also discussed. It is found that ring-opening polymerization of α-amino acid-N-carboxyanhydrides (NCA) is advantageous over the polycondensation because ring-opening polymerization, which is a chain polymerization is capable of providing polypeptides with precise topology. Results show that the system is suitable to synthesize NCA and poly(amino acid) from amino acids having acid-sensitive protecting groups.
Self-assembled spin-labeled nanoparticles based on poly(amino acids)
Hubina,Pogodaev,Sharoyko,Vlakh,Tennikova
, p. 173 - 180 (2016)
The development of detectable nanoparticles for controlled drug delivery systems has tremendous practical importance regarding the monitoring of drug pathway in organism. Self-assembly amphiphilic block-copolymer poly(l-glutamic acid)-b-poly(l-phenylalanine) (pGlu-b-pPhe) was chosen for the preparation of discussed nanoparticles. The synthesis of blocks was carried out using ring-opening polymerization (ROP) of N-carboxyanhydrides of mentioned amino acids. To introduce the spin label at C-terminal position of hydrophilic block, (4-amino-2,2,6,6-tetramethylpiperidin-1-yl)oxyl (4-amino-TEMPO) was applied as ROP initiator and the polymerization of hydrophobic block was carried out with previously synthesized macroinitiator. The results obtained by transmission electron microscopy clearly showed that TEMPO-pGlu-b-pPhe polymer was really capable to self-assembling in aqueous solutions followed by polymersome formation. The mean size of nanoparticles was increased in a range of TEMPO-pGlu43-b-pPhe12 43-b-pPhe29 43-b-pPhe49 as 60 200 280 nm, respectively. EPR spectroscopy of the solutions of spin-labeled homopolymer TEMPO-p-γ-Glu(Bzl), block copolymers TEMPO-p-γ-Glu(Bzl)-b-pPhe and suspension of polymersomes formed from TEMPO-p-Glu-b-pPhe was performed and the results were compared. It was proved that in the case of nanoparticles EPR detectable spin labels are located on polymersome surface. The experiments in cell culture demonstrated the absence of cytotoxicity of labeled nanoparticles. Additionally, it was shown that TEMPO-label can be detected inside the cell by EPR method.
An in vivo evaluation of amphiphilic, biodegradable peptide copolymers as siRNA delivery agents
Barrett, Stephanie E.,Abrams, Marc T.,Burke, Rob,Carr, Brian A.,Crocker, Louis S.,Garbaccio, Robert M.,Howell, Bonnie J.,Kemp, Eric A.,Kowtoniuk, Robert A.,Latham, Andrew H.,Leander, Karen R.,Leone, Anthony M.,Patel, Mihir,Pechenov, Sergey,Pudvah, Nicole T.,Riley, Sean,Sepp-Lorenzino, Laura,Walsh, Eileen S.,Williams, J. Michael,Colletti, Steven L.
, p. 58 - 67 (2014)
A series of amphiphilic, biodegradable polypeptide copolymers were prepared for the delivery of siRNA (short interfering ribonucleic acid). The molecular weight (or polymer chain length) of the linear polymer was controlled by reaction stoichiometry for the 11.5, 17.2, and 24.6 kDa polypeptides, and the highest molecular weight polypeptide was prepared using a sequential addition method to obtain a polypeptide having a molecular weight of 38.6 kDa. These polymers were used to prepare polymer conjugate systems designed to target and deliver an apolipoprotein B (ApoB) siRNA to hepatocyte cells and to help delineate the effect of polymer molecular weight or polymer chain length on siRNA delivery in vivo. A clear trend in increasing potency was found with increasing molecular weight of the polymers examined (at a constant polymer:siRNA (w/w) ratio), with minimal toxicity found. Furthermore, the biodegradability of these polymer conjugates was examined and demonstrates the potential of these systems as siRNA delivery vectors.
