: Platelets are stored at 22-24°C for 5 days, with gentle agitation. Platelet storage lesion decreases efficacy and safety of stored platelets. L-Carnitine is a nonessential amino acid. Its interference with arachidonic acid metabolism affects platelet functions and oxidative stress. Hence, our study focuses on the use of L-carnitine in storage solution and investigates its influence on platelet functions and oxidative stress. Platelets isolated from 4-month-old male Wistar rats were stored with and without L-carnitine (10, 50 and 100 mmol/l) at 22°C for 12 days. Various markers were analyzed on days 0, 4, 8 and 12. Aggregation with collagen decreased in LC100 (day 12), whereas adenosine triphosphate secretion increased in all L-carnitine groups. Glucose consumption was less in L-carnitine groups and pH was maintained at 7.4 in LC50 (day 8). Conjugate dienes (day 4) and thiobarbituric acid reactive substances (day 8) increased in LC10 and LC100. Protein carbonyls were maintained in L-carnitine groups. Catalase activity and total antioxidant capacity increased gradually. L-Carnitine proved to be beneficial in platelet storage solution. There was improvement in platelet metabolism, decrements in lipid peroxidation and elevations in total antioxidant capacity up to 12 days. However, pH results emphasize that platelets with L-carnitine (50 mmol/l) could be stored up to 8 days. Therefore, Tyrode's buffer with L-carnitine can be an effective storage solution for extended platelet storage. This study contributes towards the development of better storage solutions for platelets.

2016-01-01·Biochimica et Biophysica Acta (BBA) - General Subjects

Using solution X-ray scattering to determine the high-resolution structure and morphology of PEGylated liposomal doxorubicin nanodrugs

Article

作者: Barenholz, Y ; Raviv, U ; Wei, X ; Schilt, Y ; Berman, T

BACKGROUNDAmong nanodrugs, PEGylated nanoliposomes loaded with an active agent are of major importance. In this paper we studied the structures and morphology of PEGylated nanoliposomes before and after remote loading with doxorubicin.METHODSHigh-resolution structures were obtained by solution X-ray scattering combined with our advanced analysis tools. We studied the PEGylated liposomal doxorubicin (PLD) product Doxil(®), and its generics, where remote doxorubicin loading is performed by a gradient of ammonium sulfate, and LC100, a novel PLD under development, where remote loading was done by a gradient of ammonium methanesulfonate. The PLD structures were compared with drug-free nanoliposomes having identical composition.RESULTSWe determined the membrane electron density profiles of the empty and loaded PLDs, the thickness and density of the PEG layers, and the structure of the drug inside the liposomes.CONCLUSIONSThe liposomal membranes had the same structure for both ammonium salts. We found that the drug formed crystals inside PLDs loaded by ammonium sulfate, whereas it had an amorphous morphology in the PLD loaded by ammonium methanesulfonate. The variations of the drug's structural parameters between the generics of Doxil(®) are similar to the variations between batches of the same product, suggesting that all these products were structurally similar.GENERAL SIGNIFICANCEThis paper demonstrates that solution X-ray scattering, when combined with our powerful analysis tools, can determine the high-resolution structure of complex non-crystallized nanoparticle dispersions used in nanomedicine, thereby providing useful physical insights into their functions.

2012-05-01·Clinical Neuropharmacology4区 · 医学

Pharmacokinetics of Levodopa/Carbidopa Microtablets Versus Levodopa/Benserazide and Levodopa/Carbidopa in Healthy Volunteers

4区 · 医学

Article

作者: Nyholm, Dag ; Baeckstroem, Tobias ; Lewander, Tommy ; Ehrnebo, Mats ; Nystroem, Christer ; Panagiotidis, Georgios ; Gomes-Trolin, Cecilia ; Aquilonius, Sten-Magnus

OBJECTIVESTo compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration.METHODSA single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation.RESULTSThe LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence.CONCLUSIONSThe new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.

100 项与 LC-100 相关的药物交易

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