Rapid Electrochemical Screening of Phenylketonuria Maker Depending on Dehydrogenase Attached to the Pt-Doped Reduced Graphene Oxide Nanocomposites.

Phenylketonuria (PKU) is a common disease associated with amino acid metabolism, and usually occurs in newborns. It can cause serious neurological diseases and even death. However, owing to inadequate-effective treatment, it can only be slowed by a low-phenylalanine (Phe) diet. In addition, PKU screening is essential for newborns in many countries. Therefore, rapid screening is crucial for preventing damage and meeting the large sample diagnosis demand. For confirmed patients, a convenient method to monitor their regular Phe levels is required. However, current clinical methods do not meet the rapid screening and convenient monitoring requirements. Herein, a rapid and facile electrochemical device based on platinum-doped reduced graphene oxide nanocomposites was developed to detect PKU biomarker-Phe. The results demonstrated that the developed electrode has great sensitivity, selectivity, and stability. The detection range was 0.0001 mM to 6 mM with a limit of detection of 0.01 µM. Therefore, this work offers a simple and rapid method for point-of-care PKU screening and daily monitoring.

Methotrexate-loaded biodegradable polymeric micelles for lymphoma therapy.

Drug resistance and recurrence are the main clinical challenges in chemotherapy of lymphoma. Methotrexate (MTX), especially high dose MTX (HD MTX), is extensively used to treat some aggressive subtypes of lymphoma, such as Burkitt's lymphoma, in order to overcome drug resistance. But poor solubility of the free drug and severe side effects of HD MTX limit its clinical application. Polymeric micelle, as an ideal nano delivery system, provides effective solutions to these problems. In this work, monomethyl poly (ethylene glycol)-poly (ε-caprolactone) (MPEG-PCL) was employed to load MTX through a one-step solid dispersion method. MTX loaded micelles had a small particle size of 25.64 ±â€¯0.99 nm and polydisperse index (PDI) of 0.176 ±â€¯0.05. Drug loading and encapsulation efficiency of MTX loaded micelles were 5.57 ±â€¯0.14% and 92.46 ±â€¯2.38%. Compared with free MTX, MTX loaded micelles demonstrated a much slower and sustained release behavior in vitro. MTT assay and cell apoptosis study suggested that MTX loaded micelles were more effective in inhibiting proliferation and inducing apoptosis on Raji lymphoma cells than MTX injection, which was especially distinct in high dose groups. Cellular uptake study indicated that MPEG-PCL micelle had a 1.5 times higher uptake rate in Raji cells. As for in vivo studies, MTX loaded micelles were more competent to suppress tumor growth and prolong survival time than MTX injection in the subcutaneous Raji lymphoma model. Notably, the high dose group of micelle formulation exhibited the strongest anti-tumor effect without additional toxicity. Furthermore, immunofluorescent and immunohistochemical studies showed that tumors of MPEG-PCL-MTX treated mice had more apoptotic cells and fewer proliferative cells. In conclusion, MPEG-PCL-MTX micelle is an excellent intravenously injectable formulation of MTX with both good solubility and enhanced anti-tumor activity, which perfectly meets clinical demands, especially for administration of HD MTX.

[Micromeritic evaluation of the direct compression excipient LubriTose AN].

This study is to report the evaluation of the micromeritic properties of LubriTose AN, which is expected to provide preliminary theoretical basis for the direct compression technology. From the aspects of flowability, compressibility and dilution potential, the angle of repose, flow velocity, the Carr' index, tensile strength, elastic recovery, yield pressure and the lubricating ability of LubriTose AN were determined. Also, model drugs were selected to investigate the dilute potential under the desirable compressing performance. Compared to the physical mixtures, the flowability of LubriTose AN was better, and the deformation mechanism was the same with anhydrous lactose, both brittle deformation. The compressibility and compaction of LubriTose AN was slightly better than that of physical mixtures under low and moderate pressure. The dilution potential of LubriTose AN were high for most of hydrophobic drugs. The lubricate ability was desirable under different rotational speeds. LubriTose AN is an excellent co-processed excipient, which is helpful for the promotion and improvement of the tablet manufacturing level.