A large quantity synthesis of ZnO nanoneedles and their polarity determination.

A large quantity of uniform ZnO nanoneedles has been synthesized by thermal evaporation method. Both single and double tip ZnO nanoneedles were found coexistence in the as-synthesized products. The single tip nanoneedles are major products in the synthesis and a few double tip nanoneedles were also observed. The polarity of the nanoneedles was characterized by convergent beam electron diffraction (CBED) and the simulation results reveal that the polarity of the ZnO (0001) surface directs the preferential growth of the nanoneedles. It is also found that most of the double tip nanoneedles are originated from the joint growth of two single tip nanoneedles with a kink in the middle and smooth ones might be generated from forming thin layer of cubic structures in the double nanoneedle tips. A large quantity of ZnO nanorod building blocks without tips was also achieved by fast cooling. The formation of the nanoneedles and nanorods can be attributed to different cooling speeds in our experiments. The sharp single nanoneedle tip can be potentially used as scanning probe microscope or field-emission tips.

Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.

Transdermal testosterone delivery in castrated Yucatan minipigs: pharmacokinetics and metabolism.

The feasibility of using the castrated Yucatan minipig as a hypogonadal animal model to investigate the transdermal controlled systemic delivery of testosterone was studied. During a 24 h application of a testosterone transdermal delivery device (T-TDD), serial blood samples were withdrawn from the minipigs, without anesthesia, at predetermined time intervals and the plasma concentrations of testosterone as well as its major metabolites, dihydrotestosterone and estradiol, were assayed by radioimmunoassay. The compartmental pharmacokinetic modeling analysis of the plasma profiles of total testosterone indicated that as much as 92% of the total testosterone dose released from the T-TDD had been delivered transdermally into the systemic circulation during the initial rapid input period (the first 11 h of the application), while only 8% was delivered during the slow input period (up to 23h). Good correlation was observed between the in vivo input doses [1.9 (+/- 0.2), 4.8 (+/- 0.2) and 6.4 (+/- 0.5) mg/day], determined by the Wagner-Nelson equation, and the daily doses released [1.9 +/- (0.2), 4.7 (+/- 0.2) and 6.6 (+/- 0.5) mg/day, respectively, for 1, 2, and 3 units of T-TDD]. While the in vivo rate of input in the castrated minipigs was observed to be similar to that in hypogonadal men treated with the T-TDD during the first 8 h period, the input rate was found to be slower during the last 12 h. The agreement could suggest that the mechanism for the transdermal systemic delivery of testosterone in the castrated minipig could be similar to that in the hypogonadal men. However, the plasma testosterone profiles attained in the castrated minipigs were observed to be similar to, but slightly lower than that in the hypogonadal men reported in the literature. The delta Cmax (baseline normalized peak plasma concentration) and delta Cavg (baseline normalized average plasma concentration) data in the castrated minipigs were 40 and 44%, respectively, of that in hypogonadal men. The approximately 2.4 fold lower values in delta Cmax and delta Cavg data could result from the difference in the clearance rate of testosterone which approximately 2.8 fold higher in minipigs than in the human. Despite the difference in clearance rate, the castrated minipigs could be a suitable large animal model for studying the pharmacokinetics of testosterone delivered transdermally in human with hypogonadism.

[Therapeutic effect of pyronaridine in plain tablets and enteric-coated tablets in falciparum malaria patients].

A new oral dosage regimen and formulation of pyronaridine basing on the pharmacokinetic studies and a theoretical dosage regimen reported previously, was clinically evaluated for its therapeutic and undesirable effects on falciparum malaria patients in west Hainan Province, where chloroquine-resistant falciparum malaria was prevalent. 32 cases were treated with pyronaridine by the new dosage regimen of 0.5 g in d1, and 0.3g in d2 in plain tablets (group A), while additional 32 patients received enteric-coated tablets of pyronaridine by the current dosage regimen as a control (group B), which was 0.4 g x 2 on d1, and 0.4g on d2. The average fever clearance time for A and B groups was 27.0 +/- 14.1 and 30.2 +/- 13.8h respectively (P greater than 0.05), and the clearance time for asexual parasites was 57.2 +/- 10.2 and 57.9 +/- 8.7h. Upon 28d following-up examination the cure rates were found to be 100% in group A and 93.8% in group B. The undesirable responses were recorded in 18.8% of group A patients (6/32), and 28.1% of group B (9/32) respectively, and they were light and tolerable and short in time duration. It was shown that the new dosage regimen of pyronaridine could retain the same therapeutic effect as that currently used, although the total dose was reduced by one third. Hence, an important basis was provided for more rational use and further study of pyronaridine in malaria therapy.