Ultrasound controlled paclitaxel releasing system-A novel method for improving the availability of coronary artery drug coated balloon.

OBJECTIVES: The aim of this study is to improve local-drug delivery efficiency and tissue absorption using the ultrasound (US)-responsible drug coating based on a newly developed US-controlled paclitaxel release balloon. BACKGROUND: Low availability of the drug coating remains a major concern of the current drug coated balloon (DCB). The goal of this study is to develop a method to use an US-responsible paclitaxel-loaded microcapsules (PM) as the main content of balloon drug coating to enhance bioavailability of DCB. METHODS: An US-controlled paclitaxel release balloon is designed and fabricated based on the US-responsible paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) microcapsules. Rapid exchange percutaneous transluminal coronary angioplasty (PTCA) balloon catheters were coated with the PM. The deployment processes of the paclitaxel-loaded microcapsules coated balloons (PMCB) under US, PMCB without US and a homogenous matrix of paclitaxel and iopromide coated balloon (PICB) were then placed in healthy and stent implanted porcine coronary arteries. RESULTS: In vitro release assay demonstrated an ability of US (1 MHz, 1.22 W/cm2 , 1 minute) to affect the release kinetics of paclitaxel from PM by inducing a 76 ± 5.4% increase in the rate of release. The paclitaxel content in target vessels are 203 ± 37 µg/g for PMCB under US, 85 ± 23 µg/g for PMCB without US, and 107 ± 31 µg/g for PICB 1-hr post-surgery. The availability of the drug for the PMCB reaches 27% under US. CONCLUSIONS: The US-controlled paclitaxel release balloon significantly improved the drug content of the target vessels in the porcine model.

[Progress in Research Drug Eluting Stents Drug-looding and Drug Release Kinetics].

Drug eluting stents are one of the main devices of coronary intervention, which play a therapeutic role through the combination of medical devices. Drug is an important part of the drug eluting stents. The loading method, the type of carrier, drug and carrier interaction and the preparation process of the drug directly affect the drugs release kinetics characteristics of the device and the final treatment. According to the characteristics of the drug coating, drug coated stents can be divided into non-degradable polymers drug coated stents, biodegradable polymers drug coated stents and polymer-free drug eluting stents. This article discussed the stent coating process and drug release kinetics of the three types of drug eluting stent.

Research on elastic recoil and restoration of vessel pulsatility of Zn-Cu biodegradable coronary stents.

Coronary stents made of zinc (Zn)-0.8 copper (Cu) (in wt%) alloy were developed as biodegradable metal stents (Zn-Cu stents) in this study. The mechanical properties of the Zn-Cu stents and the possible gain effects were characterized by in vitro and in vivo experiments compared with 316L stainless steel stents (316L stents). Young's modulus of the as-extruded Zn-0.8Cu alloy and properties of the stents, including their intrinsic elastic recoil, stent trackability were evaluated compared with 316L stents. In vivo study was also conducted to evaluate restoration of pulsatility of vessel segment implanted stents. Both Zn-Cu stents and 316L stents have good acute lumen gain. By comparison, the advantages of Zn-Cu stents are as follows: (I) Zn-Cu stents have less intrinsic elastic recoil than 316L stents; (II) stent trackability indicates that Zn-Cu stents have a smaller push force when passing through curved blood vessels, which may cause less mechanical stimulation to blood vessels; (III) in vivo study suggests that Zn-Cu stents implantation better facilitates the recovery of vascular pulsatility.

An abluminal biodegradable polymer sirolimus-eluting stent versus a durable polymer everolimus-eluting stent in patients undergoing coronary revascularization: 3-year clinical outcomes of a randomized non-inferiority trial.

The Cordimax stent has proved non-inferior to the Cypher Select durable polymer sirolimus-eluting stent for the primary endpoint of angiographic in-stent late luminal loss and in-stent mean diameter stenosis at 9 months. The trial was designed to compare the efficacy and safety of the Cordimax stent with the Xience V stent in patients undergoing coronary revascularization. This randomized, multicenter trial enrolled 3697 patients treated with Cordimax stent (2460 patients) and Xience V stent (1237 patients). The primary efficacy endpoint was a target-lesion failure (TLF) at 1 year and the primary safety endpoint was a composite of death or myocardial infarction (MI) at 3 years. 3399 patients (91.9%) completed 3-year follow-up. At 1 year, the primary efficacy endpoint occurred in 86 (3.5%) patients in the Cordimax group versus 40 (3.2%) patients in the Xience V group (0.3% absolute risk difference, 95% CI -1.0-1.5%, Pnon-inferiority < 0.0001). At 3 years, the primary safety endpoint occurred in 39 (1.6%) patients in the Cordimax group versus 19 (1.5%) patients in the Xience V group (0.05% absolute risk difference, 95% CI -0.8-0.9%, Pnon-inferiority < 0.0001). The incidence of target lesion revascularization was low in Cordimax group compared with Xience V group (3.6% versus 5.1%, P = 0.03). There were no differences between Cordimax and Xience V in terms of Cardiac death (0.3% versus 0.4%, P = 0.70), myocardial infarction (1.2% versus 0.9%, P = 0.37), and the stent thrombosis (0.4% versus 0.6%, P = 0.61). In conclusion, safety and efficacy outcomes of Cordimax stent were non-inferior to the Xience V stent 3 years after stent implantation.

Cationic Conjugated Polymer/Hyaluronan-Doxorubicin Complex for Sensitive Fluorescence Detection of Hyaluronidase and Tumor-Targeting Drug Delivery and Imaging.

Hyaluronidase (HAase) is becoming a new type of tumor marker since it has been demonstrated to be overexpressed in various kinds of cancer cells. In this study, we described a novel fluorescence method for sensitive, rapid, and convenient HAase detection and tumor-targeting drug delivery and imaging, using a probe prepared by electrostatic assembly of a cationic conjugated polymer (CCP) and anionic hyaluronan (HA) conjugated with the anticancer drug doxorubicin (Dox). The CCP we used was poly{[9,9-bis(6'-(N,N,N-diethylmethylammonium)hexyl)-2,7-fluorenylene ethynylene]-alt-co-[2,5-bis(3'-(N,N,N-diethylmethylammonium)-1'-oxapropyl)-1,4-phenylene]} tetraiodide (PFEP). HA is a natural mucopolysaccharide that can be hydrolyzed by HAase into fragments with low molecular weights. In the PFEP/HA-Dox complex, the fluorescence of PFEP was efficiently quenched due to electron transfer from PFEP to Dox. After the PFEP/HA-Dox complex was exposed to HAase or was taken up by cancer cells through the specific binding between HA and CD44 receptor, HA was degraded by HAase to release the Dox, leading to the recovery of PFEP fluorescence to the "turn-on" state. Moreover, the degree of fluorescence recovery was quantitatively correlated with the concentrations of HAase. Compared with many previously reported methods, our work did not require laborious multiple modifications of HA that may affect the activity of HAase. This point, combined with the excellent optoelectronic property of conjugated polymer, endowed this method with high sensitivity (detection limit: 0.075 U/mL), high specificity, and rapid response, making it applicable for reliable and routine detection of HAase. This fluorescent probe was successfully utilized to detect HAase levels in human urine samples; furthermore, it can also be employed as a multifunctional system by realizing tumor-targeting drug delivery and cell imaging simultaneously. The development of this fluorescence method showed promising potential for early tumor diagnosis and therapy based on HAase detection.

Preparation and characterization of silver/TiO2 composite hollow spheres.

Silver-coated poly(methyl acrylic acid) (PSA) core-shell colloid particles were prepared by an in situ chemical reduction method. Crystalline silver/titania composite hollow spheres were obtained by coating the as-prepared PSA/silver particles with an amorphous titania layer and subsequently calcining in Ar atmosphere. SEM and TEM investigation indicated that the size of the as-prepared PSA/silver and PSA/silver/TiO(2) core-shell particles and silver/titania composite hollow particles was fairly uniform and the wall thickness of the hollow spheres was in the range of 40-80 nm. UV-vis absorption spectra were recorded to investigate their optical properties.

Cationic conjugated polymer/fluoresceinamine-hyaluronan complex for sensitive fluorescence detection of CD44 and tumor-targeted cell imaging.

Simple, rapid, and sensitive detection of CD44 is of paramount importance since it plays pivotal roles in tumor initiation, growth and metastasis. Herein, we describe a novel method for sensitive, visual and facile fluorescence detection of CD44 and CD44-mediated cancer cell imaging, using a probe based on cationic conjugated polymer (CCP)-PFEP and fluoresceinamine-hyaluronan (FA-HA). HA is an anionic natural glycosaminoglycan that can specifically bind to the overexpressed CD44 on various kinds of cancer cells. PFEP and FA-HA formed a complex through electronic interactions, resulting in a highly efficient fluorescence resonance energy transfer (FRET) from PFEP to FA-HA; moreover, the efficiencies of FRET correlated with the concentrations of CD44 because the specific binding of HA-CD44 would separate FA-HA away from PFEP. This method did not require laborious and expensive dual-labeling or protein-labeling needed in previously reported detection methods of CD44. Just mix the sample and test solution containing the PFEP/FA-HA complex, and the results allowed naked-eye detection by observing fluorescent color of solutions with the assistance of a UV lamp. Most importantly, the use of a conjugated polymer with excellent amplification property as well as the specific binding of HA-CD44 endowed this method with high sensitivity and specificity, making it applicable for reliable quantitative detection of CD44. Furthermore, the PFEP/FA-HA complex formed nanoparticles in aqueous solution, and the nanoparticles can be selectively taken up by MCF-7 cells (cancer cell) through the HA-CD44 interaction, thereby giving rise to a dual-color tumor-targeted imaging probe with good photostability. The development of this fluorescent probe showed promising potential to make a reliable and routine method available for early diagnosis of cancer.