Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats.

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple- or single-dose oral and transdermal administration. Venous blood was collected at preset intervals in single- and multiple-dose studies. Non-compartmental pharmacokinetics was analysed for all formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and 8.21 ± 0.89 mg/kg, respectively. The maximum plasma concentration was lower and the half-life longer after patch administration than oral and IV administration. Memantine bioavailability was 41 and 63% for oral and patch administration, respectively. Steady state was achieved around 24 hr for oral and patch administration. The mean AUC increased after oral or patch administration from single to multiple dose. The memantine patch formulation displayed a longer duration of action and lower peak plasma concentration. However, drug exposure was similar to the oral formulation at each dose. Additionally, the memantine patch formulation displayed a smaller interindividual variability and lower accumulation than the oral formulation.

Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran.

In this study, we prepared adriamycin (ADR)-encapsulated core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer and evaluated its antitumor activity in vitro and in vivo. The particle size of ADR-encapsulated DexLG nanoparticles was around 50-200 nm and the morphology was spherical shapes at transmission electron microscopy (TEM) observation. Since reconstitution of lyophilized nanoparticles is essential to practical use in vivo, ADR-encapsulated DexLG nanoparticles were lyophilized and reconstituted them into deionized water. Although reconstitution process caused increase of particle size, drug release behavior of nanoparticles was not significantly changed before and after reconstitution process. The ADR-encapsulated DexLG nanoparticles were less cytotoxic than free ADR plus empty nanoparticles at in vitro, while empty DexLG nanoparticles did not significantly affect cell viability. Even if free ADR plus empty nanoparticles are most effective to inhibit tumor growth at tumor-induced animal model using CT-26 cells, ADR-encapsulated DexLG nanoparticles showed increased survivability of mice. These results indicated that ADR-encapsulated DexLG nanoparticles are promising vehicles for antitumor drug delivery.

Cytotoxicity of amphotericin B-incorporated polymeric micelles composed of poly(DL-lactide-co-glycolide)/dextran graft copolymer.

In this study, we prepared amphotericin B (AmpB)-encapsulated polymeric micelle of poly(DL-lactideco-glycolide) (PLGA) grafted-dextran (DexLG) copolymer for the cytotoxicity test. The average particle size of AmpB-encapsulated DexLG polymeric micelles was around 30 approximately 70 nm and their morphology showed spherical shapes. Since aggregation states of AmpB are related to intrinsic cytotoxicity, prevention of AmpB aggregation in aqueous solution will provide low cytotoxicity and increased antimicrobial activity for the infectious disease. At UV/VIS spectrum measurement, polymeric micelle prepared from methanol/water mixture (method B) showed a monomeric state of AmpB while polymeric micelle prepared from DMSO (method A) showed an aggregated state. During the hemolysis activity test, polymeric micelle from method B showed reduced hemolysis activity compared to AmpB itself and polymeric micelle from method A. These results indicated that AmpB-incorporated polymeric micelle prepared from methanol/water mixture has low cytotoxicity and favorable antimicrobial activity.