Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

The taste of drugs has an important impact on the compliance of patients, but most of the active drug ingredients have an uncomfortable taste, especially traditional Chinese medicine. Through a variety of pharmaceutical excipients with taste masking properties combined with corresponding technologies can improve the taste of drugs and the characteristics of other dosage forms, so as to improve patient compliance. Here, we mainly summarize the auxiliary materials used for taste masking, explain the mechanism of taste masking from the point of view of excipients and introduces related uses, so as to provide reference for further research on taste masking of pediatric preparations.

Good medicine tastes bitter, but it is often difficult to swallow because the drug is bitter and astringent, so that the compliance of patients with medication is poor. However, the use of taste masking technology can better improve this situation. Appropriate and effective taste masking technology can improve the drug compliance of patients, especially children, it can also improve the curative effect and the clinical value of drugs. Herein, we summarize the latest research progress of taste masking technology, and summarize the traditional taste masking technology from the aspects of action mechanisms and application scopes. Finally, the novel and efficient taste masking technologies were presented.

As a basic amino acid, histidine has a pK_a close to the acidity of the tumor microenvironment, thus the charge and solubility of histidine are able to vary as the pH changes. Under a neutral environment, histidine is not charged and exhibits hydrophobic properties, while it can be protonated and becomes hydrophilic when exposed to mildly acidic pH, such as tumor microenvironment. Therefore, histidine is widely used in the design of drug delivery systems to target the mildly acidic pH of tumor microenvironment. This article reviews the recent progresses of histidine-based tumor-targeting drug delivery systems, and summarizes the principles on promoting internalization and tuning drug release by taking advantage of histidine. Finally, we point out the common issues on histidine application and illustrate its future prospects.

In this paper, the low-field nuclear magnetic resonance technology CPMG (Carr-Purcell-Meiboom-Gill) echo method was used to determine the cross-linking degree and cross-linking density of crospovidone (PVPP) from different manufacturers. Based on the seven physical properties of PVPP, a fingerprint spectrum (radar chart) of twenty secondary quality indicators were obtained, and three compressibility evaluation indicators, index of the parameter (IP), index of parametric profile (IPP), index of good compression (IGC) were calculated by the fingerprint spectrum. It was found that the cross-linking degree and compressibility index IP of PVPP showed a strong correlation (r = 0.816) by the correlation analysis, indicating that the cross-linking degree is one of the key quality attributes for evaluating the compressibility of PVPP.

italic>K-values of 56 batches of 7 types of povidone were measured by microfluidic rheometry and with a Ubbelohde capillary viscometer. The K-values of the two methods were tested by SPSS software and the results showed that there was no significant difference between the two methods (P > 0.05). Taking K-values measured with the Ubbelohde capillary viscometer (K_u) as the abscissa and K-values measured by microfluidic rheometry (K_m) as the ordinate a linear equation was calculated: K_m = 0.893 9K_u + 4.617 6, R² = 0.986 2, with good linearity, indicating that the microfluidic rheometer method can replace the Ubbelohde capillary viscometer in determining K-values of povidone. The microfluidic rheometer method has the benefits of less sample consumption, faster determination, and is more accurate, and it can be used with high-throughput automatic acquisition, which provides a more convenient method for the determination of K-values of different types of povidone. The weight-average molecular weights (M_w) of each type of povidone were measured by gel permeation chromatography-multi angle laser light scattering (GPC-MALLS), and the relationship between M_w and K_m was lgM_w = -0.000 4 K_m² + 0.072 7 K_m + 2.791, R² = 0.990 1. The fitting relationship was good, and M_w could be calculated by K_m by the equation.

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

In order to establish a more perfect evaluation system for dryness effect of Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma，and further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness. The healthy rats were given with different doses of water extract and volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for 21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency, the amount of drinking water, tissue morphology of submandibular glands, urine volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood rheology, ratio of cAMP/cGMP in serum and the content of Na⁺-K⁺-ATP enzyme were selected as the evaluation indexes. The results indicated that the rats with high dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and content of Na⁺-K⁺-ATP enzyme in the serum（<0.05）as compared with the soybean oil group; meanwhile, atrophy of submandibular acinar gland was obvious，and the expression of aquaporin 2 was reduced significantly（<0.05）. There were significant differences between volatile oil high dose group of raw Atractylodis Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma. There was no significant difference between the water extract groups of raw and stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation system for the dryness effect of Atractylodis Rhizoma was established. It was confirmed that the volatile oil part was the main dry part of Atractylodis Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma was not only related to the decrease of the total content of the volatile oil, but also may be related to the transformation of dryness components in the volatile oil. It provides references for the study of material basis of Atractylodis Rhizoma dryness, provides an experimental basis for the clinical application of Atractylodis Rhizoma, further clarifies the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the evaluation of other dry traditional Chinese medicines.

The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
Antineoplastic Agents ; chemistry ; toxicity ; Cell Survival ; drug effects ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drug Design ; HeLa Cells ; Humans ; Micelles ; Particle Size ; Podophyllotoxin ; analogs & derivatives ; chemistry ; toxicity ; Polyesters ; chemistry ; Polyethylene Glycols ; chemistry ; Solubility ; Surface Properties