Biodistribution and long-term fate of silver nanoparticles functionalized with bovine serum albumin in rats.

Silver nanocrystals (Ag NCs) hold promising antibiotic and antiviral properties in biological systems. The biodistribution of silver nanostructures injected into animals in vivo is currently unknown, remaining as a fundamental issue for potential therapeutic applications. Here, we injected Ag NCs capped with bovine serum albumin (BSA) in live rats to elucidate their fate in several organs including liver, heart and brain. Very significant accumulations of nanoparticles were confirmed by inductively coupled plasma mass spectroscopy (ICPMS) and transmission electron microscopy (TEM) techniques on the liver and heart. In contrast, the brain tissue did not reveal evidence of particles content. Our results suggest that Ag+ permeated across the blood-brain barrier (BBB), and followed swift clearance from the organ.

Evaluation of the bioequivalence of single 100-mg doses of two oral formulations of cyclosporin A microemulsion: a randomized, open-label, two-period crossover study in healthy adult male Mexican volunteers.

BACKGROUND: Cyclosporin A is widely used in Mexico as immunosuppressive therapy in organ transplantation and in the treatment of autoimmune disorders. Although several generic oral formulations of cyclosporin A are available in Mexico, information concerning the bioequivalence of these formulations in the Mexican population is not available in the published literature. OBJECTIVE: The aim of this study was to compare the bioequivalence and tolerability of a generic (test) and a branded (reference) soft-gelatin capsule formulation of cyclosporin A microemulsion 100 mg available in Mexico. METHODS: This randomized, open-label, 2-period cross-over study was performed at the Universidad Autónomade Nuevo León, Monterrey, México. Eligible subjects were healthy male volunteers who were randomly assigned to receive a single 100-mg dose of the test or reference formulation, followed by a 2-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(max), AUC(0-t), and AUC(0-infinity) , blood samples were obtained at intervals over the 48-hour period after dosing. The formulations were considered bioequivalent if the log-transformed ratios of Cma x and AUC were within the predetermined equivalence range (80%-125%). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events. RESULTS: Thirty-six male subjects (mean age, 22.08 years [range, 18-29 years]; mean weight, 78.23 kg [range, 72-89 kg]; mean height, 177 cm [range, 169-185 cm]) were enrolled in the study, and 34 (17 each randomized to receive the test or reference formulation first) completed it. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-infinity) were 85.12 to 92.85, 92.14 to 99.75, and 92.19 to 99.72, respectively (all, P <0.05). Similar results were found for the data without log-transformation. No adverse events occurred or were reported by patients during the study. CONCLUSIONS: In this small study in healthy adult male Mexican volunteers, a single 100-mg dose of the test formulation was bioequivalent to a single 100-mg dose of the reference formulation based on the regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

Bioavailability of two oral formulations of loratadine 20 mg with concomitant ketoconazole: an open-label, randomized, two-period crossover comparison in healthy Mexican adult volunteers.

BACKGROUND: Loratadine is a long-acting antihistamine with selective peripheral histamine H(1)-receptor antagonistic activity and fewer sedative effects compared with conventional antihistamines, and is widely used in Mexico. Although several generic formulations of loratadine are available in Mexico, based on a literature search, information concerning the bioavailability of each formulation in the Mexican population is not available. OBJECTIVE: The aim of this study was to compare the bioavailability and tolerability of 2 oral formulations of loratadine 20 mg (two 10-mg tablets) used in Mexico: Sensibit (test formulation; Laboratorios Liomont S.A. de C.V., Mexico City, Mexico) and Clarityne (reference formulation; Schering-Plough S.A. de C.V., Mexico City, Mexico) in healthy volunteers. METHODS: This open-label, randomized, 2-period crossover study was conducted at Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico. Eligible subjects were healthy male Mexican volunteers aged > or=18 years. Subjects were randomly assigned to receive a single 20-mg dose (two 10-mg tablets) of the test or reference formulation, followed by a 2-week washout period, followed by the same dose of the alternate formulation. A 400-mg dose of ketoconazole (2 doses in 24 hours) was administered to each subject before the administration of each formulation, and a 200-mg dose of ketoconazole was given together with each formulation (ie, a total of 600 mg of ketoconazole was administered). Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including C(maX), AUC(0-t), and AUC(0-infinity), blood samples were drawn at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 5, 8, 12, 16, and 22 hours after dosing. The formulations were considered bioequivalent if the geometric mean ratios of C(maX) and AUC were within the predetermined equivalence range of 80% to 125%. Tolerability was assessed by monitoring vital signs and subject interview regarding the potential presence of adverse events (AEs). RESULTS: Thirty-two subjects were enrolled in the study (mean age, 22 years [range, 18-28 years]; mean weight, 68.9 kg [range, 58-79 kg]; mean height, 170.8 cm [range, 158-183 cm]). Sixteen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding ratios of CmaX, AUC(0-t), and AUC(0-infinity) were 81.43% to 106.01%, 83.12% to 100.23%, and 84.06% to 101.10% (all, P < 0.05), meeting the predetermined criteria for bioequivalence. Similar results were found for data without a logarithmic transformation. No AEs were reported throughout the study. CONCLUSIONS: In this small study in healthy Mexican volunteers, a single, 20-mg dose of the test formulation of loratadine was found to be bioequivalent to that of the reference formulation based on the rate and extent of absorption when concomitantly administered with ketoconazole. Both formulations were well tolerated.