Synthesis of deuterium-labeled 2-quinoxalinecarboxylic acid and 3-methylquinoxaline-2-carboxylic acid from deuterium aniline.

An efficient and simple synthetic route of deuterium-labeled 2-quinoxalinecarboxylic acid-d (QCA-d ) and 3-methylquinoxaline-2-carboxylic acid-d (MQCA-d ) is presented with 99.9% and 99.6% isotopic enrichment using aniline-d as labeled starting material.

Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy.

The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together.

Dehydroascorbic Acids-modified Polymer Micelles Target Cancer Cells to Enhance Anti-tumor Efficacy of Paclitaxel.

Paclitaxel (PTX), especially albumin-bound PTX in clinical, has displayed significant inhibition of tumor growth in patients. But the systemic distribution and poor water solubility of PTX often lead to severe side effects, consequently limiting the anti-tumor efficacy. In this study, we developed a novel PTX-loaded polymeric micelle drug delivery system.

Construction of polymer-paclitaxel conjugate linked via a disulfide bond.

Covalently linked amphiphilic polymer-paclitaxel (PTX) could self-assemble into micelles to overcome many drawbacks of existing delivery systems of PTX by virtue of tunable compositions, variable sizes, high drug loading content and zero burst release. Moreover, a reduction-responsive system based on glutathione (GSH) can be established by introducing disulfide bonds into the polymeric carriers to improve the selectivity for cancer cells. Herein, we reported a disulfide bond linked polymer-PTX, P(PEGMEA)-co-P(PDPHEMA)-g-PTX with a high PTX loading content of 43.

The potential of follicle-stimulating hormone peptide-modified triptolide-loaded nanoparticles to induce a mouse model of premature ovarian insufficiency.

The use of triptolide (TP) is limited by its poor water solubility and severe toxicity. In this study, we developed an active drug delivery system (TP-loaded nanoparticles) that could help improve the water solubility of TP and decrease its toxicity. Then, we investigated whether TP-loaded nanoparticles could be used to establish a novel premature ovarian insufficiency mouse model.

Design of controlled drug delivery system based on disulfide cleavage trigger.

The disulfide bond has drawn increasing attention for the application on controlled drug delivery systems (CDDSs) due to its high redox sensibility, which is derived from the fact that the concentration of glutathione (GSH), a disulfide-bond-breaking agent, in the tumor tissue is 1000-fold higher than that in the blood plasma and the normal tissue. Thus, a disulfide is an ideal candidate for serving as the drug release trigger of CDDSs, which would be stable in the blood circulation and be broken when it reached the tumor tissue. However, improvements are still required in designing the structure of CDDSs and the drug loading patterns for CDDSs, which are important to the performance of CDDSs.

Polymerizable disulfide paclitaxel prodrug for controlled drug delivery.

A polymerizable disulfide paclitaxel (PTX) prodrug was synthesized by the consequential esterification reactions of 3,3'-dithiodipropionic acid (DTPA), a disulfide compound containing two active carboxyl groups, with 2-hydroxyethyl methacrylate (HEMA) and PTX. The structure of the prodrug was confirmed by (1)H NMR characterization. Then, the polymerizable prodrug was copolymerized with poly(ethylene glycol) methyl ether methacrylate (PEGMEA) to obtain a copolymer with hydrophilic PEG side chains and PTX covalently linked onto the backbone via disulfide bonds.

Mechanistic study of the covalent loading of paclitaxel via disulfide linkers for controlled drug release.

A novel controlled drug-delivery system (CDDS) based on fluorescent mesoporous silica nanoparticles (FMSN) covalently linked with paclitaxel (PTX) via a disulfide linker was designed and characterized. A PTX prodrug based on a disulfide linker was synthesized, and its drug-delivery mechanism was determined through HPLC characterization. Utilizing the carboxyl group of the prodrug, PTX was covalently conjugated to the surface of amino-functionalized FMSN, with a disulfide linker as a spacer to bridge between PTX and FMSN, and the loading content of PTX reached as high as 13% by weight.

Preparation of copolymer paclitaxel covalently linked via a disulfide bond and its application on controlled drug delivery.

A novel controlled drug delivery system based on copolymer covalently linked paclitaxel via a disulfide bond was constructed. Copolymer with poly(ethylene glycol) (PEG) side chains and carboxyl groups on the backbone was prepared by radical copolymerization of tert-butyl acrylate and poly(ethylene glycol) methyl ether acrylate, followed by selectively hydrolyzing tert-butyl groups to carboxyl groups. Utilizing the carboxyl group as an active reaction site, paclitaxel, a well-known chemotherapeutic drug, could be covalently linked to the backbone of a copolymer via a disulfide bond, and the loading content of paclitaxel could reach up to 32 wt %.