127090-71-5Relevant articles and documents
Acid degradable and biocompatible polymeric nanoparticles for the potential codelivery of therapeutic agents
Duong, Hien T. T.,Marquis, Christopher P.,Whittaker, Michael,Davis, Thomas P.,Boyer, Cyrille
, p. 8008 - 8019 (2011)
The synthesis of well-defined functional nanoparticles for the encapsulation of hydrophobic and hydrophilic drugs is described. Nanoparticles were built from amphiphilic copolymers consisting of P(OEG-A) homopolymers chain extended with vinyl benzyl chloride (VBC) and pentafluorophenyl acrylate (PFP-A) comonomers. Subsequently, the pendant chlorine atoms, introduced into the chains by VBC units, were substituted using sodium methanethiosulfonate, yielding copolymer chains with methanethiosulfonate (MTS) pendant functionality. The thiol/MTS exchange chemistry afforded by the MTS groups was then used to introduce different functional groups by reacting with a range of thiols. These copolymers were self-assembled in water yielding nanoparticles with sizes of ～20 nm. The activated esters in the copolymer were used to cross-link the nanoparticles with difunctional amino compounds (cross-linkers). A cross-linker bearing an acid cleavable bond (ketal) was used to generate pH-sensitive core-shell nanoparticles. Drug encapsulation and release was modeled using hydrophobic (Nile Red) and hydrophilic (thiol-modified fluorescein isothiocyanate, FITC) dye molecules. The release of each dye was monitored using UV-vis spectroscopy, demonstrating the possibility of selective release of single dye or the simultaneous release of both dyes depending on the experimental stimuli. An in vitro study confirmed that the nanoparticles were nontoxic to the NIH-3T3 cell line. Cell uptake analysis by flow cytometry and fluorescence microscopy indicated a higher uptake for cross-linked nanoparticles than for non-cross-linked nanoparticles.
Formulation of Acid-Sensitive Micelles for Delivery of Cabazitaxel into Prostate Cancer Cells
Aydin, Omer,Youssef, Ibrahim,Yuksel Durmaz, Yasemin,Tiruchinapally, Gopinath,Elsayed, Mohamed E. H.
, p. 1413 - 1429 (2016)
We report the synthesis of an amphiphilic triblock copolymer composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a hydrophobic poly(methyl methacrylate) (PMMA) block using atom transfer radical polymerization technique. We examined the self-assembly of PEG-b-PAA-b-PMMA copolymers in aqueous solutions forming nanosized micelles and their ability to encapsulate hydrophobic guest molecules such as Nile Red (NR) dye and cabazitaxel (CTX, an anticancer drug). We used 2,2β′-(propane-2,2-diylbis(oxy))-diethanamine to react with the carboxylic acid groups of the central PAA block forming acid-labile, shell cross-linked micelles (SCLM). We investigated the loading efficiency and release of different guest molecules from non-cross-linked micelles (NSCLM) and shell cross-linked micelles (SCLM) prepared by reacting 50% (SCLM-50) and 100% (SCLM-100) of the carboxylic acid groups in the PAA in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions as a function of time. We examined the uptake of NR-loaded NSCLM, SCLM-50, and SCLM-100 micelles into PC-3 and C4-2B prostate cancer cells and the effect of different micelle compositions on membrane fluidity of both cell lines. We also investigated the effect of CTX-loaded NSCLM, SCLM-50, and SCLM-100 micelles on the viability of PC-3 and C4-2B cancer cells compared to free CTX as a function of drug concentration. Results show that PEG-b-PAA-b-PMMA polymers form micelles at concentrations ≥11 μg/mL with an average size of 40-50 nm. CTX was encapsulated in PEG-b-PAA-b-PMMA micelles with 55% loading efficiency in NSCLM. In vitro release studies showed that 30% and 85% of the loaded CTX was released from SCLM-50 micelles in physiologic (pH 7.4) and acidic (pH 5.0) buffer solutions over 30 h, confirming micelles' sensitivity to solution pH. Results show uptake of NSCLM and SCLM into prostate cancer cells delivering their chemotherapeutic cargo, which triggered efficient cancer cell death. PEG-b-PAA-b-PMMA micelles were not hemolytic and did not cause platelet aggregation, which indicate their biocompatibility.
Dual Location, Dual Acidic pH/Reduction-Responsive Degradable Block Copolymer: Synthesis and Investigation of Ketal Linkage Instability under ATRP Conditions
Jazani, Arman Moini,Oh, Jung Kwon
, p. 9427 - 9436 (2017)
Stimuli-responsive degradation (SRD) undergoing chemical transition through the cleavage of labile linkages has been proved to dramatically increase the versatility of stimuli-responsive block copolymers. In particular, dual or multiple stimuli-responsive degradable block copolymers that can be triggered by two endogenous stimuli of acidic pH and reduction are in high demand. Here, a new strategy utilizing atom transfer radical polymerization (ATRP) is reported to synthesize a dual acidic pH/reduction-responsive degradable block copolymer (DLDSRD) labeled with an acidic pH-labile ketal linkage at the block junction and pendant reductively cleavable disulfide groups in hydrophobic block at dual locations. A robust route with multiple steps utilizing carbamate chemistry to endow stability during protection/deprotection steps enables the synthesis of a novel poly(ethylene glycol)-based ATRP macroinitiator labeled with a ketal linkage (PEG-ketal-Br macroinitiator). Conducting ATRP allows for the synthesis of a series of DLDSRD diblock copolymers consisting of a hydrophilic poly(ethylene glycol) block covalently conjugated through a ketal linkage with a hydrophobic polymethacrylate block having multiple disulfide pendants. Analysis shows an unexpectedly high degree of polymerization of the hydrophobic polymethacrylate block that could be attributed to the instability of ketal linkages under ATRP conditions. The preliminary results from aqueous micellization and dual acidic pH/reduction-responsive cleavage of ketal and disulfide linkages suggest the feasibility of DLDSRD-based nanoassemblies toward effective drug delivery exhibiting precisely controlled release in response to dual stimuli at dual locations (core and interfaces).
Method for continuously preparing degradable curing agent based on tubular reaction device
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Paragraph 0056-0109, (2020/05/30)
The invention discloses a method for continuously preparing a degradable curing agent based on a tubular reaction device. Continuous synthesis, separation and solvent application are achieved throughthe solubility difference of raw material alkamine salt and product diamino acetal salt in a reaction solution; the reaction solution containing saturated diamino acetal salt after separation does notneed to be separated, and can be directly fed to a reaction system again to be subjected to a condensation substitution reaction after the raw material is supplemented. According to the method for continuously preparing the degradable curing agent by adopting the tubular reaction device, an existing intermittent production mode is changed, the product yield is greatly improved, the reaction period is shortened, the yield is increased, the productivity is improved, and the method has the characteristics of simple process, mild reaction conditions and environmental friendliness.
SALTS OF DIAMINOACETALS AND DIAMINOKETALS AND THEIR SYNTHESIS, AND THEIR TRANSFORMATIONS TO DIAMINOACETALS AND DIAMINOKETALS
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Paragraph 0381-0382, (2019/02/01)
This application relates, in part, to novel salts represented by the following structure of Formula (1): wherein R1a is selected from the group consisting of hydrogen and optionally substituted alkyl (e.g., unsubstituted C1-6 alkyl, e.g., —CH3); R1b is optionally substituted alkyl (e.g., unsubstituted C1-6 alkyl, e.g., —CH3); each occurrence of R2 and R3 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, and optionally substituted aryl; R2 and R3 can combine with each other to form optionally substituted cycloalkyl; each m and n is independently an integer ranging from 1 to 20 (e.g., m and n is independently an integer ranging from 1 to 5); and each of Q1? and Q2? is independently a counterion (e.g., each of Q1? and Q2? is independently a counterion selected from the group consisting of chloride, bromide, fluoride, iodide, acetate, carboxylate, hydrogen sulfate, nitrate, and phenolate, and sulfonate, e.g., chloride), and methods of making the same.
