Aripiprazole-montmorillonite: a new organic-inorganic nanohybrid material for biomedical applications.

Poor aqueous solubility and the unpleasant taste of aripiprazole (APZ) have been recurring problems, owing to its low bioavailability and low patient tolerance, respectively. Herein, we prepared a nanohybrid system that was based on a bentonite clay material, montmorillonite (MMT), which could both mask the taste and enhance the solubility of APZ (i.e., APZ-MMT). To further improve the efficacy of this taste masking and drug solubility, APZ-MMT was also coated with a cationic polymer, polyvinylacetal diethylamino acetate (AEA). In vitro dissolution tests at neutral pH showed that the amount of drug that was released from the AEA-coated APZ-MMT was greatly suppressed (<1%) for the first 3 min, thus suggesting that AEA-coated APZ-MMT has strong potential for the taste masking of APZ. Notably, in simulated gastric juice at pH 1.2, the total percentage of APZ that was released within the first 2 h increased up to 95% for AEA-coated APZ-MMT. Furthermore, this in vitro release profile was also similar to that of Abilify®, a commercially available medication. In vivo experiments by using Sprague-Dawley rats were also performed to compare the pharmacokinetics of AEA-coated APZ-MMT and Abilify®. AEA-coated APZ-MMT exhibited about 20% higher systemic exposure of APZ and its metabolite, dehydro-APZ, compared with Abilify®. Therefore, a new MMT-based nanovehicle, which is coated with a cationic polymer, can act as a promising delivery system for both taste masking and for enhancing the bioavailability of APZ.

A nanohybrid system for taste masking of sildenafil.

A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN-MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN-MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 ± 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN-MMT and Viagra(®), an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN-MMT during the first 2 hours while almost 100% of drug was released from Viagra(®). However, an in vivo experiment showed that the AEA-coated SDN-MMT exhibited higher drug exposure than Viagra(®). For the AEA-coated SDN-MMT, the area under the plasma concentration- time curve from 0 hours to infinity (AUC(0-∞)) and maximum concentration (C(max)) were 78.8 ± 2.32 µg · hour/mL and 12.4 ± 0.673 µg/mL, respectively, both of which were larger than those obtained with Viagra(®) (AUC(0-∞) = 69.2 ± 3.19 µg · hour/mL; C(max) = 10.5 ± 0.641 µg/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure.

Influence of naphthalene biodegradation on the adhesion of Pseudomonas putida NCIB 9816-4 to a naphthalene-contaminated soil.

In an earlier study, Pseudomonas putida NCIB 9816-4, which was one of the most studied naphthalene-degrading bacteria, showed the preferred adhesion to the naphthalene-contaminated soil when it was in the exponential growth phase. The adhesion was found to take place through a hydrophobic interaction. We postulated that the surface hydrophobicity of P. putida NCIB 9816-4 in the exponential growth phase might be increased during the uptake of naphthalene, which caused the preferred adhesion to the naphthalene-contaminated soil. To verify this postulate, a plasmid-cured strain of P. putida NCIB 9816-4 was obtained in this study and compared with the wild-type for adhesion to the naphthalene-contaminated soil. Only the wild-type in the exponential growth phase showed increased adhesion to naphthalene-contaminated soil. The water contact angles of the two strains were measured in the presence and in the absence of naphthalene as indices of surface hydrophobicity. The water contact angle of the wild-type increased in the presence of naphthalene, whereas that of the cured strain did not change. We conclude that the uptake of naphthalene during naphthalene biodegradation in the exponential growth phase of P. putida NCIB 9816-4 made the cell surface more hydrophobic, resulting in increased adhesion to naphthalene-contaminated soil.

Enhanced production of manganese peroxidase from immobilized Phanerochaete chrysosporium due to the increased autolysis of chlamydospore-like cells.

The autolysis of chlamydospore-like cells in Phanerochaete chrysosporium immobilized in polyurethane foam correlated with the production of manganese peroxidase (MnP). The maximum specific activity of MnP was 1055 U g dry mycelium(-1) in the immobilized culture, compared with 260 U g dry mycelium(-1) in the submerged culture. Scattered mycelial pellets were formed in the immobilized culture in which almost all of the chlamydospore-like cells were subject to autolysis. However, highly crowded pellets were formed in the free culture, in which only the chlamydospore-like cells in the exterior were subject to autolysis. We propose that the enhanced production of MnP in immobilized cultures of P. chrysosporium is due to increased autolysis of the chlamydospore-like cells.