N1,N12-Diacyl Spermines: SAR Studies on Non-viral Lipopolyamine Vectors for Plasmid DNA and siRNA Formulation

Purpose  

To study the efficiency of novel synthetic N ¹,N ¹²-diacyl spermines on DNA and siRNA binding, and to compare their transfection efficiency with viability in cell lines.     

String-Like Micellar Nanoparticles Formed by Complexation of PEG-<Emphasis Type="Italic">b</Emphasis>-PPA and Plasmid DNA and Their Transfection Efficiency

Purpose  

To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion.     

Trial and Error: How the Unclonable Human Mitochondrial Genome was Cloned in Yeast

Purpose  

Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochondrial genome has been dubbed unclonable in E. coli, due to regions of instability in the D-loop and tRNA^Thr gene.     

Association between PLA2G12A polymorphism and patients with schizophrenia in a southern Chinese Han population

Background

Elevated phospholipase A2 (PLA2) activity is reported to be involved in the development of schizophrenia. Further study revealed an association between PLA2 groups XIIA (PLA2G12A) polymorphism and patients with schizophrenia in a northeast Chinese Han population.

Objective

This study will further examine whether PLA2G12A rs3087494 polymorphism is associated with patients with schizophrenia in a southern Chinese Han population.

Methods

This polymorphism was genotyped in 438 patients with schizophrenia (diagnosed according to Diagnostic and Statistical Manual of Mental Disorders‐IV) and 876 healthy controls using a case–control design. Demographic and clinical data were collected in all subjects.

Results

The allele and genotype frequencies of PLA2G12A rs3087494 polymorphism significantly differed between groups (both, p < .001). These differences still were significant by adjusting for sex and age. However, there was no difference in age at onset among 3 genotype groups in patients with schizophrenia by adjusting for the variables (F = 0.22, p = .80). Stepwise multivariate regression analysis showed that this polymorphism was not associated with age at onset in patients with schizophrenia (β = .008, t = .07, p = .94).

Conclusions

Our results indicated that even though PLA2G12A rs3087494 polymorphism did not influence age at onset in patients with schizophrenia, it may play an important role in the susceptibility to schizophrenia in a southern Chinese Han population.     

Wound healing potential of Solanum xanthocarpum in streptozotocin‐induced diabetic rats

Objectives

The objective of the present study was to evaluate wound healing potential of Solanum xanthocarpum extract in streptozotocin‐induced diabetic rats.

Methods

Alcoholic extract of the aerial parts (ESX ) was subjected to phytochemical estimations and its standardization with chlorogenic acid using HPLC . ESX was then evaluated for wound healing potential in, streptozotocin‐induced diabetic rats using excision and incision wound models on topical and oral treatment Various biochemical evaluations, such as collagen, hexosamine, hyaluronic acid, protein, DNA along with antioxidant parameters, proinflammatory cytokines, VEGF and histopathological examination were also evaluated.

Key findings

Extract of S. xanthocarpum depicted the presence of mainly alkaloids, polyphenols, steroids, while content of chlorogenic acid was found to be 8.44% w/w. The maximum effective nature of ESX in healing was observed at 10% gel (topical) and 200 mg/kg (orally) in diabetic rats, where highest healing power was observed when treated both orally and topically. Biochemical evaluations showed significant increase in the levels of collagen, hexosamine, hyaluronic acid, protein, DNA followed by significant decline in the levels of blood glucose, lipid peroxidation, nitric oxide and expression of proinflammatory cytokines, supported by histopathology.

Conclusions

The potential healing effect in diabetic rats may be attributed to the presence of chlorogenic acid in combination with other phytoconstituents.

     

pH-Sensitive Multi-PEGylated Block Copolymer as a Bioresponsive pDNA Delivery Vector

Purpose  

A reversibly-PEGylated diblock copolymer, poly(aspartate-hydrazide-poly(ethylene glycol))-block-poly(aspartate-diaminoethane) (p[Asp(Hyd-PEG)]-b-p[Asp(DET)]) was reported here for enhanced gene transfection and colloidal stability. The diblock copolymer possessed a unique architecture based on a poly(aspartamide) backbone. The first block, p[Asp(Hyd)], was used for multi-PEG conjugations, and the second block, p[Asp(DET)], was used for DNA condensation and endosomal escape.     

Higher serotonin transporter availability in early‐onset obsessive–compulsive disorder patients undergoing escitalopram treatment: A [11C]DASB PET study

Objective

Early‐onset obsessive–compulsive disorder (EOCD) and late‐onset obsessive–compulsive disorder (LOCD) are distinct subtypes of obsessive–compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet.

Methods

Six EOCD and 6 LOCD patients were enrolled. They underwent serial [¹¹C]DASB positron emission tomography scans during maintenance therapy with escitalopram, and their plasma concentration of escitalopram was measured simultaneously with the scan. Then, the drug‐free binding potential of SERT was calculated by pharmacokinetic–pharmacodynamic modelling.

Results

In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = ?.580, p = .048) with age of onset of the disease, but not with the Yale–Brown Obsessive Compulsive Scale scores.

Conclusions

These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long‐term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.     

Population <Emphasis Type="Italic">In Vitro</Emphasis>-<Emphasis Type="Italic">In Vivo</Emphasis> Correlation Model for Pramipexole Slow-Release Oral Formulations

Purpose  

To establish an in vitro-in vivo level A correlation (IVIVC) for pramipexole slow-release formulations.     

A Semi-mechanistic Modeling Strategy to Link <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Drug Release for Modified Release Formulations

Purpose  

To develop a semi-mechanistic model linking in vitro to in vivo drug release.     

Predicting Intestinal Precipitation—A Case Example for a Basic BCS Class II Drug

Purpose  

To investigate the prediction accuracy of in vitro and in vitro/in silico methods for in vivo intestinal precipitation of basic BCS class II drugs in humans.     

Promoted Transfection Efficiency of pDNA Polyplexes-Loaded Biodegradable Microparticles Containing Acid-Labile Segments and Galactose Grafts

Purpose  

Targeting to antigen-presenting cells and efficient intracellular delivery of pDNA are essential for development of microsphere formulations of DNA vaccine.     

Development and In Vitro-In Vivo Evaluation of Fenretinide-Loaded Oral Mucoadhesive Patches for Site-Specific Chemoprevention of Oral Cancer

Purpose  

To develop fenretinide oral mucoadhesive patch formulations and evaluate their in vitro and in vivo release performance for future site-specific chemoprevention of oral cancer.     

Microneedle Arrays Allow Lower Microbial Penetration Than Hypodermic Needles <Emphasis Type="BoldItalic">In Vitro</Emphasis>

Methods  

In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models.     

Prediction of Human Metabolic Clearance from <Emphasis Type="Italic">In Vitro</Emphasis> Systems: Retrospective Analysis and Prospective View

Purpose  

To provide a definitive assessment of prediction of in vivo CL _int from human liver in vitro systems for assessment of typical underprediction.     

New Fluorescent Probes Targeting the Mitochondrial-Located Translocator Protein 18 kDa (TSPO) as Activated Microglia Imaging Agents

Purpose  

To evaluate the utility of new Translocator protein 18 kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia.     

Prostate Cancer-Targeted Imaging Using Magnetofluorescent Polymeric Nanoparticles Functionalized with Bombesin

Purpose  

In this work, the aim was to prepare and characterize a magnetofluorescent polymeric nanoparticle for prostate cancer imaging in vivo.     

Development of New Localized Drug Delivery System Based on Ceftriaxone-Sulbactam Composite Drug Impregnated Porous Hydroxyapatite: A Systematic Approach for <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Animal Trial

Purpose  

Present investigation deals with an extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis, using hydroxyapatite porous scaffolds.     

Characterization of a Microsphere Formulation Containing Glucose Oxidase and its <Emphasis Type="BoldItalic">In Vivo</Emphasis> Efficacy in a Murine Solid Tumor Model

Purpose  

This work focused on the characterization and in vitro/in vivo evaluation of an alginate/chitosan microsphere (ACMS) formulation of glucose oxidase (GOX) for the locoregional delivery of reactive oxygen species for the treatment of solid tumors.     

Do CYP3A and ABCB1 genotypes influence the plasma concentration and clinical outcome of donepezil treatment?

Purpose  

The aim of our study was to evaluate the impact of CYP3A4, CYP3A5, and ABCB1 polymorphisms on donepezil disposition and clinical outcome.