Local gene delivery via endovascular stents coated with dodecylated chitosan–plasmid DNA nanoparticles

Development of efficacious therapeutic strategies to prevent and inhibit the occurrences of restenosis after percutaneous transluminal coronary angioplasty is critical for the treatment of cardiovascular diseases. In this study, the feasibility and efficiency of stents coated with dodecylated chitosan–plasmid DNA nanoparticles (DCDNPs) were evaluated as scaffolds for localized and prolonged delivery of reporter genes into the diseased blood vessel wall. Dodecylated chitosan–plasmid DNA complexes formed stable positive charged nanospheres with mean diameter of approximately 90–180 nm and zeta potential of +28 ± 3 mV. As prepared DCDNPs were spray-coated on stents, a thin layer of dense DCDNPs was successfully distributed onto the metal struts of the endovascular stents as demonstrated by scanning electron microscopy. The DCDNP stents were characterized for the release kinetics of plasmid DNA, and further evaluated for gene delivery and expression both in vitro and in vivo. In cell culture, DCDNP stents containing plasmid EGFP-C1 exhibited high level of GFP expression in cells grown on the stent surface and along the adjacent area. In animal studies, reporter gene activity was observed in the region of the artery in contact with the DCDNP stents, but not in adjacent arterial segments or distal organs. The DCDNP stent provides a very promising strategy for cardiovascular gene therapy

Qualitative Analysis of Visible Foreign Solids in Armillarisin A Injection Formulations Using Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry

During the trial production of Armillarisin A for injection (AA-I), unidentified needle-like yellow-brown crystals were occasionally observed. Here, we report an ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS) method for determining the source of the visible foreign bodies in the formulations of Armillarisin A active pharmaceutical ingredient (AA-API). AA-API, photolyzed samples, the intermediate polymer, and the excipient analyzed determined after the separation on a Waters Symmetry C18 (3.5 μm, 4.6 × 75 mm) column with a mobile phase consisting of a methanol/acetic acid (0.1 mol/L) aqueous solution (50:50). Furthermore, the crystal type of the visible foreign bodies, the intermediate polymer and AA-API were investigated by X-ray powder diffraction (XRD). The results revealed that the characteristics of the visible foreign solids were the same as those of AA-API as regards UPLC peak position (368 nm) and MS spectrum in negative ion detection mode. The visible foreign solids were thus identified as unpolymerized crystals of AA-API and were attributed to AA-API itself. The results showed that the production process could be improved by changing the stirring method and frequency as well as by optimizing the polymerization temperature to ensure the safety, stability, and control of the product quality in the stage of batch production

A Simple and Accurate Method for the Determination of Related Substances in Coenzyme Q10 Soft Capsules

As a new dosage form, coenzyme Q10 (Co-Q10) soft capsules are easily absorbed and utilized by the human body. Co-Q10 soft capsules can effectively improve the bioavailability and reduce medical costs for patients. A main concern about Co-Q10 as an active pharmaceutical ingredient (API) is how to control the total quantity of related substances. In this article, according to the degradation pattern of the API, the most easily degradable impurity (impurity X) in the sample was prepared and its chemical structure was determined. Furthermore, a simple and accurate method was developed for the determination of related substances and to avert the interference of excipient ingredients in Co-Q10 soft capsules. The approach was validated adequately and the primary impurity X was confirmed accurately. The limit of total quantity of related substances (less than 1%) could be revised to the level of specific impurity X being no more than 0.5%, in this effective quality control method of Co-Q10 soft capsules. The revised level is suggested to be included in the corresponding standard of the supplement taken from the Pharmacopoeia of the People’s Republic of China (2015 edition). This can provide a feasible method for the relevant enterprises and regulatory authorities to control the related substances of coenzyme Q10 soft capsules