Efficient Drug Loading Method for Poorly Water-Soluble Drug into Bicelles through Passive Diffusion.

The bicelle, a type of solid lipid nanoparticle, comprises phospholipids with varying alkyl chain lengths and possesses the ability to solubilize poorly water-soluble drugs. Bicelle preparation is complicated and time-consuming because conventional drug-loading methods in bicelles require multiple rounds of thermal cycling or co-grinding with drugs and lipids. In this study, we proposed a simple drug-loading method for bicelles that utilizes passive diffusion. Drug-unloaded bicelles were placed inside a dialysis device and incubated in a saturated solution of ketoconazole (KTZ), which is a model drug. KTZ was successfully loaded into bare bicelles over time with morphological changes, and the final encapsulated concentration was dependent on the lipid concentration of the bicelles. When polyethylene glycol (PEG) chains of two different lengths (PEG2K and 5K) were incorporated into bicelles, PEG2k and PEG5k bicelles mitigated the morphological changes and improved the encapsulation rate. This mitigation of morphological changes enhanced the encapsulated drug concentration. Specifically, PEG5k bicelles, which exhibited the greatest prevention of morphological changes, had a lower encapsulated concentration after 24 h than that of PEG2k bicelles, indicating that PEGylation with a longer PEG chain length improved the loading capacity but decreased the encapsulation rate owing to the presence of a hydration layer of PEG. Thus, PEG with a certain length is more suitable for passive loading. Moreover, loading factors, such as temperature and vehicles used in the encapsulation process, affected the encapsulation rate of the drug. Taken together, the passive loading method offers high throughput with minimal resources, making it a potentially valuable approach during early drug development phases.

Multidisciplinary team approach to end-stage dialysis access patients.

BACKGROUND: The hemodialysis reliable outflow (HeRO) access device is a permanent dialysis graft used in patients with central venous obstruction. Given the complexity of care related to end-stage dialysis access (ESDA) patients, a multidisciplinary approach has been used to achieve operative success of HeRO graft placement. METHODS: The single-center retrospective review included adult patients that were seen in ESDA clinic who underwent a HeRO graft placement from September 2010-September 2014 under the care of a team consisting of a nephrologist, an interventional radiologist, and a surgeon. The effectiveness of the multidisciplinary approach was evaluated using outcome variables including successful HeRO graft placement, operative complications, the rate of obtaining central venous access, and advanced endovascular maneuvers performed by interventional radiology to obtain central venous access. RESULTS: A multidisciplinary approach has been used in 33 ESDA patients. Access to the right atrium was achieved in 100% of cases. Fifty-eight percent of patients required advanced endovascular maneuvers in the interventional radiology suite to obtain central venous access. Successful HeRO graft placement was achieved in 94% (31 of 33) of the study population. No intraoperative complications were encountered. Median primary and secondary patency rates were 83 d (interquartile range: 45-170) and 345 d (interquartile range: 146-579) per HeRO graft placement, respectively. Primary and secondary patency rates at 60 d were 70% (23 of 33) and 79% (26 of 33), respectively. CONCLUSIONS: In this difficult patient population, a multidisciplinary team can provide a unique and collaborative approach to HeRO graft placement in patients with complex central venous outflow obstruction.

A New Method for Evaluating Actual Drug Release Kinetics of Nanoparticles inside Dialysis Devices via Numerical Deconvolution.

Nanoparticle formulations have found increasing applications in modern therapies. To achieve desired treatment efficacy and safety profiles, drug release kinetics of nanoparticles must be controlled tightly. However, actual drug release kinetics of nanoparticles cannot be readily measured due to technique difficulties, although various methods have been attempted. Among existing experimental approaches, dialysis method is the most widely applied one due to its simplicity and avoidance of separating released drug from the nanoparticles. Yet this method only measures the released drug in the medium outside a dialysis device (the receiver), instead of actual drug release from the nanoparticles inside the dialysis device (the donor). Thus we proposed a new method using numerical deconvolution to evaluate actual drug release kinetics of nanoparticles inside the donor based on experimental release profiles of nanoparticles and free drug solution in the receptor determined by existing dialysis tests. Two computer programs were developed based on two different numerical methods, namely least square criteria with prescribed Weibull function or orthogonal polynomials as input function. The former was used for all analyses in this work while the latter for verifying the reliability of the predictions. Experimental data of drug release from various nanoparticle formulations obtained from different dialysis settings and membrane pore sizes were used to substantiate this approach. The results demonstrated that this method is applicable to a broad range of nanoparticle and microparticle formulations requiring no additional experiments. It is independent of particle formulations, drug release mechanisms, and testing conditions. This new method may also be used, in combination with existing dialysis devices, to develop a standardized method for quality control, in vitro-in vivo correlation, and for development of nanoparticles and other types of dispersion formulations.