Nanoparticles (NPs) have an outstanding position in pharmaceutical, biological, and medical disciplines. Polymeric NPs based on chitosan (CS) can act as excellent drug carriers because of some intrinsic beneficial properties including biocompatibility, biodegradability, non-toxicity, bioactivity, easy preparation, and targeting specificity. Drug transport and release from CS-based particulate systems depend on the extent of cross-linking, morphology, size, and density of the particulate system, as well as physicochemical properties of the drug. All these aspects have to be considered when developing new CS-based NPs as potential drug delivery systems. This comprehensive review is summarizing and discussing recent advances in CS-based NPs being developed and examined for drug delivery. From this point of view, an enhancement of CS properties by its modification is presented. An enhancement in drug delivery by CS NPs is discussed in detail focusing on (i) a brief summarization of basic characteristics of CS NPs, (ii) a categorization of preparation procedures used for CS NPs involving also recent improvements in production schemes of conventional as well as novel CS NPs, (iii) a categorization and evaluation of CS-based-nanocomposites involving their production schemes with organic polymers and inorganic material, and (iv) very recent implementations of CS NPs and nanocomposites in drug delivery.

Current antiviral therapy research is focused on developing dosage forms that enable highly effective drug delivery, providing a selective effect in the organism, lower risk of adverse effects, a lower dose of active pharmaceutical ingredients, and minimal toxicity. In this article, antiviral drugs and the mechanisms of their action are summarized at the beginning as a prerequisite background to develop relevant drug delivery/carrier systems for them, classified and briefly discussed subsequently. Many of the recent studies aim at different types of synthetic, semisynthetic, and natural polymers serving as a favorable matrix for the antiviral drug carrier. Besides a wider view of different antiviral delivery systems, this review focuses on advances in antiviral drug delivery systems based on chitosan (CS) and derivatized CS carriers. CS and its derivatives are evaluated concerning methods of their preparation, their basic characteristics and properties, approaches to the incorporation of an antiviral drug in the CS polymer as well as CS nanoparticulate systems, and their recent biomedical applications in the context of actual antiviral therapy. The degree of development (i.e., research study, in vitro/ex vivo/in vivo preclinical testing), as well as benefits and limitations of CS polymer and CS nanoparticulate drug delivery systems, are reported for particular viral diseases and corresponding antivirotics.

Determination of thiopurine S-methyltransferase activity by hydrophilic interaction liquid chromatography hyphenated with mass spectrometry, Journal of Pharmaceutical and Biomedical Analysishttp://dx.doi.org/10. 1016/j.jpba.2017.05.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 Highlights New HILIC-HPLC-MS method was developed for determination of TPMT activity  HILIC-HPLC-MS combination was approved by excellent performance parameters  HILIC-HPLC-MS was compared to traditional RP-HPLC-UV as well as advanced RP-HPLC-MS  Conventional approaches were surpassed in terms of selectivity, LOD, analysis time  HILIC-HPLC-MS is favorable for routine assay of 6-MMP/6-MP ratio in RBC lysates List of abbreviations6-MMP -6-methylmercaptopurine, 6-MP -6-mercaptopurine, 6-TG -6-thioguanine, AZA -azathioprine, Cl-P -6-chloropurine, DTT -dithiothreitol, IBD -inflammatory bowel diseases, RBC -red blood cells, SAM -S-adenosyl-L-methionine, TGN -thioguanine nucleotides, TPMT -thiopurine-S-methyl transferase. IndroductionThiopurine drugs, namely azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), are immunosuppressive agents that are, due to their low cost and high effectiveness, widely used in the treatment of inflammatory bowel diseases (IBD), but also in other autoimmune diseases, some hemopoetic disorders and some solid organ transplant [1][2][3][4][5]. However, the occurrence of adverse drug reactions limits the use of these drugs. Up to 15 % of IBD patients discontinue this type of treatment due to adverse events that include nausea, skin reactions, pancreatitis, hepatotoxicity or myelotoxicity [6,7].Thiopurine drugs are prodrugs, so their biological activity is preceded by extensive metabolism. Briefly, after absorption, AZA is metabolized in the liver to 6-MP which then can be metabolized to active thioguanine nucleotides (TGN) and to inactive methylated product 6-methylmercaptopurine (6-MMP) by the thiopurine-S-methyl transferase (TPMT) enzyme [8]. TPMT (EC 2.1.1.67), a key enzyme involved in the thiopurine drug metabolism, is subject to common genetic polymorphism that leads to trimodial distribution of the TPMT activity in population [9]. Individuals with lower TPMT activity might have an increased risk of developing thiopurine-induced myelosuppression. On the contrary, individuals with high TPMT activity have lower concentrations of active TGN metabolites resulting in reduced therapeutic efficacy of the drug [10]. In addition, high TPMT activity leads to accumulation of the hepatotoxic methylated metabolites [11]. Therefore, some scientific committees advise to determine the TP...

INTRODUCTION: Despite known risk factors for developing type 2 diabetes mellitus (T2D), the research community still tries to discover new markers that would widen our diagnostic and therapeutic approach to diabetes. Therefore, research on microRNA (miR) in diabetes thrives. This study aimed to assess the utility of miR-126, miR-146a, and miR-375 as novel diagnostic markers for T2D. METHODS: We examined relative quantities of miR-126, miR-146a, and miR-375 in the serum of patients with established type 2 diabetes mellitus (n = 68) and compared these with a control group (n = 29). We also undertook a ROC analysis of signifi cantly changed miR to examine their use as a diagnostic test. RESULTS: MiR-126 (p < 0.0001) and miR-146a (p = 0.0005) showed a statistically signifi cant reduction in patients with type 2 diabetes mellitus. MiR-126 also proved to be an exceptional diagnostic test in our study cohort, with high sensitivity (91 %) and specifi city (97 %). We did not fi nd any difference in our study groups' relative quantities of miR-375. CONCLUSION: The study proved a statistically signifi cant reduction of miR-126 and miR-146a in patients with T2D (Tab. 4, Fig. 6, Ref. 51).

Polysaccharides are attractive gelling agents in pharmacy due to their safety, biocompatibility, biodegradability, relatively easy way of preparation, and low price. Due to their variable physical-chemical properties, polysaccharides have potentialities to be used for designing new drug delivery systems for controlled drug release. In this comparative study, rheological and texture properties as well as the in vitro release of model drug ibuprofen (IBU) with 11 polysaccharide-based hydrogels were investigated. The in vitro release of IBU significantly differed between (i) neutral (hydroxy/alkylcelluloses), (ii) anionic (carboxyalkylcellulose and its sodium salt, tragacanth, carrageenan, xanthan gum), and (iii) cationic (chitosans) hydrogels due to different contribution of provided interactions and viscosity within the hydrogel groups. The drug release kinetics of each hydrogel system was evaluated for five kinetic models. Several combinations of cationic hydrogels with neutral or anionic ones were performed to illustrate possibilities of providing modified IBU release profiles. In this context, chitosan was presented as an effective modifier of diffusion profiles for negatively charged drugs formulated into combined polymeric systems, providing their prolonged release. The most appropriate hydrogel for the topical application (i.e., providing favorable rheological and texture properties along with the highest drug release) was selected from a studied series of polysaccharide-based hydrogels.