Development and Validation of a Rapid RP-HPLC-DAD Analysis Method for the Simultaneous Quantitation of Paclitaxel and Lapatinib in a Polymeric Micelle Formulation

A robust and rapid analysis method was developed and validated for the simultaneous assay of paclitaxel (PTX) and lapatinib (LPT) in a polymeric micelle formulation as a novel drug delivery system using high-performance liquid chromatography (HPLC). The assay was performed using the C18 MZ-Analytical Column (5 μm, 150 × 4.6 mm, OSD-3) which was protected with the C18 pre-column (5 μm, 4.0 × 4.6 mm, OSD-3). The mobile phase was composed of acetonitrile and water (70/30; V/V) with a flow rate of 0.5 mL/min and detection wavelength of 227 nm. Accuracy was reported as the relative error and was found to be less than 6.8%. The interday assay was evaluated to be 3.22% and 5.76% RSD for PTX and LPT, respectively. The intraday precision was found to be at its maximum value of 5.83% RSD. The limit of detection for both PTX and LPT was found to be 1 µg/mL by means of the newly developed method. The limit of quantitation for PTX and LPT was found to be 5 µg/mL. The calibration curves for both drugs were linear in the concentration range of 5 to 80 μg/mL. In vitro release for both drugs from the polymeric micelle was evaluated using the newly developed analysis method.     

Modafinil Blocks Reinstatement of Extinguished Opiate-Seeking in Rats: Mediation by a Glutamate Mechanism

Opiate addiction is characterized by high rates of relapse even after long periods of abstinence, requiring new relapse-prevention treatments that do not have abuse potential. Recently, clinical studies suggested that the wake-promoting drug modafinil might decrease relapse in cocaine addicts. In addition, group II metabotropic glutamate receptors (mGlu2/3R) have been suggested as a new therapeutic target for drug addiction. Here, we investigated the ability of modafinil to prevent the acute morphine to promote reinstatement of extinguished preference for morphine, and the involvement of mGlu2/3Rs in this effect. Conditioned place preference (CPP) for morphine was induced in Sprague–Dawley rats, followed by extinction training. Preference for the morphine-paired side was reinstated following extinction by a morphine-priming injection. The results of our study showed that modafinil (300 mg/kg, i.p., but not 100 mg/kg) 30 min before the morphine-priming injection blocked reinstatement of extinguished CPP. The anti-reinstatement effect of modafinil was completely prevented by pretreatment with the selective mGlu2/3 antagonist {"type":"entrez-nucleotide","attrs":{"text":"LY341495","term_id":"1257705759"}}LY341495. Additional experiments indicated that modafinil alone did not produce a preference, and that modafinil did not alter the expression of morphine CPP or the cueing properties of morphine either 1 or 14 days after morphine CPP conditioning. These data reveal a novel mechanism for modafinil actions, a role for mGlu2/3 receptors in reinstatement of opiate-seeking, and a new therapeutic option to treat relapse in opiate addiction.     

Development of Octreotide-Loaded Chitosan and Heparin Nanoparticles: Evaluation of Surface Modification Effect on Physicochemical Properties and Macrophage Uptake

Octreotide (OCT) is a therapeutic peptide which is administered for the treatment of acromegaly. The purpose of this study was to design a new polyethylene glycol (PEG)–conjugated nanoparticle (PEG-NP) to overcome the short half-life and poor stability of OCT. The developed PEG-NPs were compared with non-PEGylated NPs with respect to their size, morphological characteristics, loading efficiency, release profile, and macrophage uptake. The OCT-loaded NPs and PEG-NPs were prepared by ionic complexion of chitosan (Cs) with either heparin (Hp) or PEGylated heparin (PEG-Hp). The chemical structure of PEG-Hp was confirmed by IR and proton nuclear magnetic resonance. Morphological analyses by scanning electron microscopy showed that NPs and PEG-NPs have a uniform shape. Dynamic laser scattering measurements indicated that hydrodynamic diameter of NPs and PEG-NPs were 222.5 ± 10.0 nm and 334.9 ± 6.7 nm, respectively. NPs and PEG-NPs had a positive zeta potential of about 32.5 ± 1.1 mv and 20.6 ± 2.4 mv, respectively. Entrapment efficiency was 61.4 ± 1.0% and 55.7 ± 2.4% for NPs and PEG-NPs, respectively. Compared with the NPs, the PEG-NPs exhibited a slower release profile. Subsequently, fluorescein isothiocyanate–labeled chitosanCs was synthesized and used to evaluate the stealth characteristic of PEG-NPs. In vitro macrophage uptake of fluorescently labeled NPs was measured by flow cytometry.     

The salivary exosomal microRNA as a potential biomarker in patients with periodontitis and oral cancers

Periodontitis and oral cancers are the most common oral diseases in the human population. The early diagnosis of oral diseases allows the efficient therapy of the patient. During oral diseases, resident cells in the affected tissue secrete exosomal microRNAs (miRNAs) into saliva. As these miRNAs have a crucial role in the pathogenesis of oral diseases, they have been suggested as non-invasive and validated biomarkers in predicting periodontitis severity and cancer progression. Several attempts have been performed to evaluate the expression of salivary exosomal miRNAs in patients with periodontitis and oral cancers. Some miRNAs are differentially expressed in the saliva of the affected patients when compared to healthy individuals. These miRNAs are reviewed in this narrative review. Collectively, it seems that salivary exosomal microRNAs could be used as a diagnostic biomarker in oral diseases. However, further studies are required to validate them.     

Long-term efficacy of conditioning training program combined with feedback on kinetics and kinematics in male runners

This study was aimed to compare the effects of 8-week conditioning training (CT) programs with and without feedback on lower limbs' biomechanics and injury incidence in free-injury male runners and assess their effectiveness across a 1-year observation. A total of 49 healthy male runners were randomly assigned to one of three groups of CT (n = 16), CT with feedback (n = 17), and placebo (n = 16) group. Kinematic and kinetic measurements were conducted at pre-intervention, 8 weeks post-intervention, and 1-year follow-up stage. Injury incidence was also measured at pre-intervention and follow-up stage. As a result, significant improvement was found in within-group differences in CT and CT with feedback groups. Moreover, significant difference in CT with feedback group was observed in the kinetic outcome improvement after 8 weeks as compared to CT group. On the other side, there were no significant differences between the CT and CT with feedback groups in kinematic outcomes. However, the percentage of changes in kinematic outcomes were higher in CT with feedback group than those in the CT group. No significant change was observed in the placebo group in all the variables. There was comparative between-group difference between CT with feedback group and the placebo one, favoring the former group. At 1-year follow-up, the injury incidence was reduced by 32% for CT group, 64.6% for CT with feedback group, and 15.5% for placebo. Thus, the CT with feedback was effective in improving biomechanics and reducing injury incidence. Improvements were generally maintained through 1 year, indicating potential for long-term changes. This study demonstrates the applicability of using feedback with CT to enhance safer movement patterns in runners and may subsequently help prevent or reduce injury risks.     

Conservation of small RNA pathways in platypus

Small RNA pathways play evolutionarily conserved roles in gene regulation and defense from parasitic nucleic acids. The character and expression patterns of small RNAs show conservation throughout animal lineages, but specific animal clades also show variations on these recurring themes, including species-specific small RNAs. The monotremes, with only platypus and four species of echidna as extant members, represent the basal branch of the mammalian lineage. Here, we examine the small RNA pathways of monotremes by deep sequencing of six platypus and echidna tissues. We find that highly conserved microRNA species display their signature tissue-specific expression patterns. In addition, we find a large rapidly evolving cluster of microRNAs on platypus chromosome X1, which is unique to monotremes. Platypus and echidna testes contain a robust Piwi-interacting (piRNA) system, which appears to be participating in ongoing transposon defense.