ABSTRACT
Even though current drug discovery provides a variety of potential drug candidates, many of those substances are difficult to formulate due to their poor water-solubility. To overcome this obstacle a technological formulation is crucial. Albumin-based nanocarriers are a possible intravenous delivery system which is already approved and commercially available. However, no universal carrier for poorly water-soluble substances is found yet. In the present study, new preparation processes for nanocapsules consisting of a medium-chain triglyceride (MCT) core and a human serum albumin (HSA) shell were developed. The nanocarrier system exhibits desirable physicochemical properties with a hydrodynamic diameter of 150 nm and a polydispersity index of 0.1. Furthermore, the nanocapsules were stable towards the addition of electrolytes and also in basic to neutral pH range. The nanocapsules were storage stable for at least 7 months at 4 °C and could also be lyophilized to reach an even longer shelf life of at least 21 months. In addition, the nanocapsule system showed no cytotoxicity in cell culture. The developed system represents a suitable carrier for a variety of different poorly water-soluble drug substances (e.g., fenofibrate, naproxen, indomethacin) showing a high potential for a universal formulation platform for further lipophilic active pharmaceutical ingredients (APIs).
ABSTRACT
BACKGROUND: Uncertainty remains regarding the optimal method of brain protection for procedures that require repair or replacement of the aortic arch. We examined the early outcomes of a technique for brain protection in patients undergoing partial aortic arch (hemiarch) replacement that involves deep hypothermic circulatory arrest (DHCA) and retrograde cerebral perfusion (RCP) of cold blood from the superior vena cava toward the end of the arrest interval. METHODS: During a recent 15-year interval, 520 patients underwent elective or urgent/emergent ascending aortic and hemiarch replacement as an isolated (47 patients) or combined (473 patients) procedure employing DHCA (mean nasopharyngeal temperature at circulatory arrest, 17.1°C and mean duration, 19.3 minutes) supplemented with RCP of cold blood from the superior vena cava toward the end of the arrest interval (mean, 6.7 minutes). The mean age of the patients was 59.5 years, and 65% were male. RESULTS: The in-hospital and 30-day mortality rates were 1.2% (six patients). Seven patients (1.4%) sustained a stroke and 19 patients (3.7%) had transient neurologic dysfunction that completely resolved by the time of hospital discharge. Four patients (0.77%) developed postoperative renal failure requiring dialysis. Twenty-one patients (4%) required ventilator support for >48 hours and five patients (0.96%) required a tracheostomy. The median hospital length of stay was 6 days. CONCLUSION: DHCA with a brief interval of RCP is a safe and effective technique for brain protection during hemiarch aortic replacement. RCP reduces the duration of brain ischemia and permits removal of particulate matter and air from the arterial circulation.
ABSTRACT
Every day, thousands of patients receive erythrocyte concentrates (ECs). They are indispensable for modern medicine, despite their limited resource. Artificial oxygen carriers (AOCs) represent a promising approach to reduce the need for ECs. One form of AOCs is perfluorodecalin-filled albumin-based nanocapsules. However, these AOCs are not storable and need to be applied directly after production. In this condition, they are not suitable as a medicinal product for practical use yet. Lyophilization (freeze drying) could provide the possibility of durable and applicable nanocapsules. In the present study, a suitable lyophilization process for perfluorodecalin-filled nanocapsules was developed. The nanocapsules were physicochemically characterized regarding capsule size, polydispersity, and oxygen capacity. Even though the perfluorodecalin-filled albumin-based nanocapsules showed a loss in oxygen capacity directly after lyophilization, they still provided a remarkable residual capacity. This capacity did not decline further for over two months of storage. Furthermore, the nanocapsule size remained unaltered for over one year. Therefore, the AOCs were still applicable and functional after long-term storage due to the successful lyophilization.
ABSTRACT
It is sometimes argued that the implementation of an overall similarity classification is less effortful than the implementation of a single-dimension classification. In the current article, we argue that the evidence securely in support of this view is limited, and report additional evidence in support of the opposite proposition--overall similarity classification is more effortful than single-dimension classification. Using a match-to-standards procedure, Experiments 1A, 1B and 2 demonstrate that concurrent load reduces the prevalence of overall similarity classification, and that this effect is robust to changes in the concurrent load task employed, the level of time pressure experienced, and the short-term memory requirements of the classification task. Experiment 3 demonstrates that participants who produced overall similarity classifications from the outset have larger working memory capacities than those who produced single-dimension classifications initially, and Experiment 4 demonstrates that instructions to respond meticulously increase the prevalence of overall similarity classification.
