RESUMO
Poly(amino acid)s (PAAs) are one kind of favorable biopolymer that can be used as a drug or gene carrier. However, conventional ring-opening polymerization of PAAs is slow and needs a strict anhydrous environment with an anhydrous reagent as well as the product without enough high molecular weight (Mn), which limits the expanding of PAAs' application. Herein, we took BLG-NCA as the monomer to quickly synthesize one kind of high Mn amphiphilic copolymer, poly(ethylene glycol)-b-poly(γ-benzyl-l-glutamic acid) (PEG-PBLG), by relay polymerization with a simple one-pot method within 3 h in mild conditions (open air, moisture insensitive). In the polymerization process, ring-opening polymerization-induced self-assembly in sodium bicarbonate aqueous solution first occurred to obtain low Mn PEG-PBLG seeds without purification. Then γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) dichloromethane solution was added into PEG-PBLG seeds directly and stirred vigorously to form am emulsion; during this process, the amphiphilic PEG-PBLG seeds will anchor on the interface of DCM and water to ensure the concentration of α-helix rigid PBLG in DCM to maintain the following relay polymerization. Then, high Mn PEG-PBLG was obtained in mild conditions in one pot. We found that the α-helix rigid structure was essential for relay polymerization by studying the synthetic speed of amphiphilic copolymer with different secondary structures. MOE simulation results showed that PBLG and BLG-NCA tended to form a double hydrogen bond, which was beneficial to relay polymerization because of higher local concentrations that can produce more double hydrogen bonds. Our strategy can quickly obtain high Mn PEG-PBLG (224.9 KDa) within 3 h from PEG-NH2 and BLG-NCA in one pot and did not need an extra initiator. After deprotection, the poly(ethylene glycol)-b-poly(l-glutamate acid) (PEG-PGA) with high Mn as a second product can be used as an excellent antitumor drug carrier. The high Mn PEG-PGA can achieve an encapsulation rate of 86.7% and a drug loading rate of 47.3%, which is twice that of the low Mn PEG-PGA. As a result, the synthesis of PEG-PBLG by relay polymerization simplified the process of PEG-PAA polymerization and increased the Mn. In addition, this method opened a way to obtain other kinds of high Mn PEG-PBLG values in the future.
Assuntos
Aminoácidos , Anidridos , Glutamatos , Polietilenoglicóis , Polietilenoglicóis/química , Aminoácidos/química , Polimerização , Ácido Glutâmico , Peso Molecular , Polímeros/química , Ácido Poliglutâmico/químicaRESUMO
BACKGROUND: A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion. METHODS: One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival. RESULTS: Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis. CONCLUSIONS: Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.