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Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated.

Background Dyslipidemia and inflammation are closely interrelated contributors in the pathogenesis of atherosclerosis. Disorders of lipid metabolism initiate an inflammatory and immune-mediated response in atherosclerosis, while low-density lipoprotein cholesterol (LDL-C) lowering has possible pleiotropic anti-inflammatory effects that extend beyond lipid lowering. Main text Activation of the immune system/inflammasome destabilizes the plaque, which makes it vulnerable to rupture, resulting in major adverse cardiac events (MACE). The activated immune system potentially accelerates atherosclerosis, and atherosclerosis activates the immune system, creating a vicious circle. LDL-C enhances inflammation, which can be measured through multiple parameters like high-sensitivity C-reactive protein (hsCRP). However, multiple studies have shown that CRP is a marker of residual risk and not, itself, a causal factor. Recently, anti-inflammatory therapy has been shown to decelerate atherosclerosis, resulting in fewer MACE. Nevertheless, an important side effect of anti-inflammatory therapy is the potential for increased infection risk, stressing the importance of only targeting patients with high residual inflammatory risk. Multiple (auto-)inflammatory diseases are potentially related to/influenced by LDL-C through inflammasome activation. Conclusions Research suggests that LDL-C induces inflammation; inflammation is of proven importance in atherosclerotic disease progression; anti-inflammatory therapies yield promise in lowering (cardiovascular) disease risk, especially in selected patients with high (remaining) inflammatory risk; and intriguing new anti-inflammatory developments, for example, in nucleotide-binding leucine-rich repeat-containing pyrine receptor inflammasome targeting, are currently underway, including novel pathway interventions such as immune cell targeting and epigenetic interference. Long-term safety should be carefully monitored for these new strategies and cost-effectiveness carefully evaluated.

The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.

Reorganized for easy use, this book provides an up-to-date reference to the tools, techniques, and science for predicting oil reservoir performance even in the most difficult fields. Topics covered in the handbook include: Processes to enhance production, Well modification to maximize oil and gas recovery, and Completion and evaluation of wells, well testing, and well surveys. This book provides solid information and insight for engineers and students alike on maximizing production from a field in order to obtain the best possible economic return. With this handbook, professionals will find a valuable reference for understanding the key relationships among the different operating variables. Examples contained in this reference demonstrate the performance of processes under forceful conditions through a wide variety of applications.

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom-up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability.

Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

One promising biomarker that has received substantial interest for the evaluation of suspected acute coronary syndromes (ACS) is copeptin. Therefore, our goal was to assess the additive value of copeptin for early diagnosis and prognosis of Non-ST segment acute coronary syndromes (NSTE-ACS). The study included ninety patients with suspected ACS. Patients with typical ischemic chest pain within six hours of symptom onset and without ST-segment elevation on electrocardiograph (ECG) were included. In addition to cardiac troponin I (cTnI), copeptin was assayed from venous blood samples obtained on admission, followed by serial troponin measurements six and twelve hours later. One year follow-up was performed for any major adverse cardiac events (MACEs) including cardiac death, re-infarction, re- hospitalization for ischemic events, heart failure, stroke and target lesion revascularization (TLR). Of seventy nine patients included in the final analysis, Forty (50.6%) were diagnosed as unstable angina (UA), while thirty nine (49.4%) had a non-ST elevation myocardial infarction (NSTEMI). Copeptin level on admission was significantly higher among NSTEMI patients than those with UA. With regard to the correlation analyses, copeptin was positively correlated with each of, Global Registry of Acute Coronary Events (GRACE), Thrombolysis In Myocardial Infarction (TIMI) and synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) scores. The sensitivity and negative predictive value (NPV) of the combination of admission copeptin and cTn-I were 100% and 100%, respectively, versus 57% and 70%, respectively, with admission of cTn-I alone. The area under curve (AUC) of the combination of copeptin and cTn-I was (0.975, p < 0.001) and was significantly higher than the AUC of cTn-I alone (0.888, p < 0.001). Admission copeptin was an independent predictor for MACEs by multiple regression analysis (OR: 0.01, 95% CI: 0.0–0.8, P = 0.04). High values of copeptin had the highest rate of MACEs and coronary revascularization during one year of follow up. The combination of copeptin and conventional troponin I aids in early rule out of NSTEMI virtually independent of chest pain onset (CPO) with high NPV in patients presenting within three hours from chest pain onset with excellent prognostic value for risk stratification and prediction of MACEs.

Background Rosuvastatin (RSV) is a poorly water-soluble drug that has an absolute oral bioavailability of only 20%. The aim of this work was to prepare a positively charged chitosan coated flexible lipid-based vesicles (chitosomes) and compare their characteristics to the corresponding negatively charged flexible liposomal nanoparticles (NPs) in order to develop new RSV nanocarrier systems. Methods Three formulation factors affecting the development of chitosomes nano-formulation were optimized for their effects on the particles size, entrapment efficiency (EE) and zeta potential. The optimized flexible chitosomes and their corresponding liposomal NPs were characterized for morphology, in vitro release, flexibility and intestinal cell viability. The half maximum inhibitory concentrations (IC50) for both formulations were calculated. Results The drug to lipid molar ratio, edge activator percent and the chitosan concentration were significantly affecting the characteristics of NPs. The optimized chitosomes nano-formulation exhibited larger size, higher EE and greater zeta potential value when compared to the corresponding liposomal NPs. Both formulations showed a spherical shape nanostructure with a marked outer shell for the chitosomes nano-formulation. Chitosomes illustrated an extended drug release profile when compared with the corresponding liposomal NPs and the prepared drug suspension. Flexibility of both vesicles was confirmed with superiority of liposomal NPs over chitosomes. RSV loaded chitosomes nano-formulation exhibited lower IC50 values and higher therapeutic window while liposomal NPs were compatible with the intestinal cells. Conclusions RSV loaded chitosomes nano-formulation could be considered as a promising nanocarrier system with a marked cytotoxic activity while, RSV loaded liposomal NPs are suitable nanocarrier to improve RSV activity in treatment of cardiovascular disorders.

Acute ST-segment elevation myocardial infarction (STEMI) is associated with left ventricular (LV) structural and functional consequences. We aimed to elucidate LV geometric changes following STEMI using three-dimensional (3D) echocardiography (3DE) and to assess their functional implications using two-dimensional (2D) speckle tracking echocardiography (STE). The study included 71 patients with STEMI who underwent baseline and 6-month follow-up 2D- and 3DE. Measured parameters included LV dimensions, biplane volumes, wall motion assessment, 2D LV global longitudinal strain (GLS), and 3D LV volumes, sphericity index and systolic dyssynchrony index. According to 3DE, LV geometric changes were classified as, adverse remodeling, reverse remodeling, and minimal LV volumetric changes. The occurrence of in-hospital and follow-up major adverse cardiovascular events (MACE) was assessed among the study population. The incidence of developing adverse remodeling was 25.4% while that of reverse remodeling was 36.6%. Adverse remodeling patients had significantly higher in-hospital MACE. Reverse remodeling was associated with significantly improved GLS, that was less evident in those with minimal LV geometric changes, and non-significant improvement for adverse remodeling group. LV baseline 2D GLS significantly correlated with follow-up 3D volumes among both reverse and adverse remodeling groups. Female gender and higher absolute GLS change upon follow-up were significantly associated with reverse remodeling. ROC-derived cutoff for adverse remodeling reallocated a substantial number of patients from the minimal change group to the adverse remodeling. Following acute STEMI, two-dimensional GLS was associated with and potentially predictive of changes in LV volumes as detected by three-dimensional echocardiography.

Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery. Three formulation factors were optimized for their effect on particle size (Y1) and entrapment efficiency (Y2) utilizing central composite experimental design. Interaction among components was studied using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Ketoconazole crystalline state was studied using X-ray powder diffraction. Six different polymeric ISG formulations were prepared and loaded with either optimized NPs or a pure drug. The prepared ISG formulations were characterized for in vitro gelation, drug release and antifungal activity. The permeation through human epithelial cell line was also investigated. The results revealed that all the studied formulation parameters significantly affected Y1 and Y2 of the developed NPs. DSC and FTIR studies illustrated compatibility among NP components, while there was a change from the crystalline state to the amorphous state of the NPs. The in vitro release from the ISG formulations loaded with drug NPs showed sustained and enhanced drug release compared to pure drug formulations. In addition, ISG loaded with NPs showed enhanced anti-fungal activity compared to pure drug formulations. Alginate-chitosan ISG formulation loaded with optimized ketoconazole NPs illustrated higher drug permeation through epithelial cell lines and is considered as an effective ophthalmic drug delivery in the treatment of fungal eye infections.