In vitro comparison of three rifampicin loading methods in a reinforced porous ß-tricalcium phosphate scaffold.

The antibiotic compound, rifampicin (RFP), was loaded into porous reinforced ß-tricalcium phosphate (ß-TCP) scaffolds using three different solution adsorption methods. This resulted in drug delivery systems (DDS) generated by vacuum adsorption (VA), dynamic adsorption (DA), and static adsorption (SA). In vitro examination of the drug loading and release profiles of the DDS indicated that the unit mass of RFP loaded into the scaffold by the VA method (0.44 mg/g) was higher than that achieved by SA (0.42 mg/g) or DA (0.38 mg/g) (P < 0.05). The mechanical strength had no significant change after RFP-loading (P > 0.05). Moreover, there were no significant differences among the mechanical strength of three ß-TCP DDS generated by loading RFP using SA, DA, and VA (P > 0.05). In vitro release testing showed an initial burst release of RFP from the three different DDS within the first 3 h and in the first 51 h, the cumulative release of RFP from VA-DDS, DA-DDS, and SA-DDS had reached 56.2, 83.6, and 88.6 %, respectively. Complete RFP release had occurred from VA-DDS, DA-DDS, and SA-DDS after 23, 17, and 15 days, respectively. As the VA-DDS method showed improved RFP loading and a more sustained drug release, this method is recommended for solution adsorption drug loading into porous ß-TCP scaffolds to form a DDS.

Synthesis, biodistribution, and imaging of PEGylated-acetylated polyamidoamine dendrimers.

Polyamidoamine (PAMAM) dendrimers have been widely used as drug carriers, non-viral gene vectors and imaging agents. However, the use of dendrimers in biological system is constrained because of inherent toxicity and organ accumulation. In this study, the strategy of acetylation and PEGylation-acetylation was used to minimize PAMAM dendrimers toxicities and to improve their biodistribution and pharmacokinetics for medical application. PEGylated-acetylated PAMAM (G4-Ac-PEG) dendrimers were synthesized by PEGylation of acetylated PAMAM dendrimer of generation 4 (G4) with acetic anhydride and polyethylene glycol (PEG) 3.4 k. To investigate the cytotoxicity and in vivo biodistribution of the conjugates, in vitro cell viability analysis, Iodine-125 (125I) imaging, tissue distribution and hematoxylin-eosin (HE) staining were performed. We find that acetylation and PEGylation-acetylation essentially eliminates the inherent dendrimer cytotoxicity in vitro. Planar gamma (gamma) camera imaging revealed that all the conjugates were slowly eliminated from the body, and higher abdominal accumulation of acetylation PAMAM dendrimer was observed. Tissue distribution analysis showed that PEGylated-acetylated dendrimers have longer blood retention and lower accumulation in organs such as the kidney and liver than the non-PEGylated-acetylated dendrimers, but acetylation only can significantly increase the accumulation of G4 in the kidney and decrease the concentration in blood. Histology results reveal that no obvious damage was observed in all groups after high dose administration. This study indicates that PEGylation-acetylation could improve the blood retention, decrease organ accumulation, and improve pharmacokinetic profile, which suggests that PEGylation-acetylation provides an alternative method for PAMAM dendrimers modification.

Embozene™ microspheres induced nonreperfused myocardial infarction in an experimental swine model.

OBJECTIVES: To develop a magnetic resonance imaging (MRI) compatible, percutaneous technique for the generation of nonreperfused myocardial infarct (MI). BACKGROUND: Modeling nontreated MI has major importance in the development and preclinical testing of new therapeutic strategies for patients missing the time window suitable for revascularization following MI. METHODS: In 31 male swine, nonreperfused MI was generated by permanent occlusion of either the LAD or LCX coronary artery using 900 µm Embozene™ microspheres. Animals were monitored for 90 min postocclusion. Surviving animals were followed up for 2 (n = 6), 4 (n = 6), 14 (n = 6), or 56 (n = 6) days. At the end of the planned study session, contrast enhanced MRI, triphenyl-tetrazolium-chloride staining, and microscopic histopathology were carried out. RESULTS: The mortality rate in this study was 22.6%. Intraoperative arrhythmias occurred in 14 cases: premature ventricular complexes with (5) or without (3) ventricular tachycardia, 2nd degree atrio-ventricular block (1), and ventricular fibrillation (6). MRI, TTC, and histology confirmed the existence of MI in every case. Macroscopic pathology showed that the microspheres caused a practically total occlusion at the epicardial level of the coronary artery. Multiple infarcts were detected in one case, probably due to unintentional reflux of the microspheres. Microspheres retained in the coronary arteries did not cause any MRI artifact. CONCLUSIONS: The generation of nonreperfused MI is feasible by percutaneous injection of Embozene into the coronary artery system. The MI model thus obtained is suitable for the purposes of MRI experiments.

A Nanoparticle-Decorated Biomolecule-Responsive Polymer Enables Robust Signaling Cascade for Biosensing.

To meet the increasing demands for ultrasensitivity in monitoring trace amounts of low-abundance early biomarkers or environmental toxins, the development of a robust sensing system is urgently needed. Here, a novel signal cascade strategy is reported via an ultrasensitive polymeric sensing system (UPSS) composed of gold nanoparticle (gNP)-decorated polymer, which enables gNP aggregation in polymeric network and electrical conductance change upon specific aptamer-based biomolecular recognition. Ultralow concentrations of thrombin (10-18 m) as well as a low molecular weight anatoxin (165 Da, 10-14 m) are detected selectively and reproducibly. The biomolecular recognition induced polymeric network shrinkage responses as well as dose-dependent responses of the UPSS are validated using in situ real-time atomic-force microscopy, representing the first instance of real-time detection of biomolecular binding-induced polymer shrinkage in soft matter. Furthermore, in situ real-time confocal laser scanning microscopy imaging reveals the dynamic process of gNP aggregation responses upon biomolecular binding.