PLANT BASED BIOAVAILABILITY ENHANCERS

Many of the synthetic as well as herbal drugs despite of their notable in vitro finding demonstrate insignificant in vivo activity majority of times due to poor bioavailability. As per Biopharmaceutical Classification System (BCS) one of the main concern is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability. To overcome these issues the various strategies have been adopted including use of permeation enhancers which are also known as bioenhancers. Bioenhancers are synthetic or natural compounds that increases the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc. into the systemic circulation and at the site of action for exhibiting improved therapeutic action. By improving bioavailability, bioenhancers can lead to reduction in drug dose, decrease in the treatment period and can circumvent the problem of drug resistance. Numerous studies have reported application of synthetic bioenhancers. On the other hand, owing to the natural origin, plant based bioenhancer can serve as better alternative. Literature review have revealed that the plant-based bioenhancers have been used in with a wide varieties of drugs including antibiotics, antiviral and anti-cancer. These can be categorized based on their sources and the mechanism of activity. This review will provide a systematic and detailed overview of the various plant based bioenhancers and applications.

Liposome assisted drug delivery-A review

Liposomes, sphere-formed vesicles consisting of one or greater phospholipid bilayers, had been first described within the mid-60s. Among numerous gifted new drug delivery systems, liposomes signify an advanced generation to supply active molecules to the site of action, and right now, numerous formulations are in clinical use. The application of liposomes to help drug shipping has already had a chief impact on many biomedical regions. They have been proven to be beneficial for stabilizing pharmaceuticals, overcoming boundaries to cellular and tissue uptake, and improving biodistribution of compounds to goal sites In vivo. This permits powerful delivery of encapsulated compounds to goal sites even as minimizing systemic toxicity. Liposomes present as an attractive transport gadget due to their wide physicochemical and biophysical properties which allow smooth manipulation to cope with exclusive shipping concerns. In this review, we will talk the advances in liposome assisted drug shipping, biological challenges, and present day medical and experimental use of liposomes for biomedical applications. The translational limitations of liposomal technology may also be provided.

Formulation and Evaluation of Fast Dissolving Tablet of Ondansetron by Utilizing Liquisolid Compact Technique

Ondansetron is an anti-emetic drug which is insoluble in water. The present study was aimed to formulate and evaluate oral fast dissolving tablet of Ondansetron by Utilizing Liquisolid Compact Technique. The tablets were prepared by direct compression method and characterized by UV, FTIR studies. Six formulations (F1-F6) of ondansetron were prepared and tablets were evaluated for weight variations, hardness, thickness, friability, disintegration time, drug content and In-vitro dissolution studies gave satisfactory result. TF6 was found to be the best and acceptable formulation whose drug content was about 99.17±0.05 and percentage (%) drug release 97.49±2.03 in 10 min, high as compare to other formulation and has low disintegration time 17±0.01 as compare to other formulation which indicates that drug is rapidly dissolved and available at the site of action.

EFECTO DE UN SURFACTANTE NO IONICO EN LA PERMEABILIDAD DE BUTORFANOL A TRAVES DE MUCOSA NASAL EQUINA

Implementation of intranasal administration for the delivery of drugs with site of action into the central nervous system, such as butorphanol, became a potential choice in equine medicine. In this study, using Franz-diffusion cells the in vitro permeation rate through respiratory and olfactory equine nasal mucosa of two butorphanol formulations was estimated and compared. Both formulations had the same composition, was the exception for formulation 2, that contained 2, 5 x 10 -4 M of a non-ionic surfactant (tween 80). Butorphanol administered dose was 24, 4 mg/cm2. Plots of the cumulative amounts of butorphanol against time were constructed, where maximum flux values at the steady state (Jss), apparent permeability coefficients (Kp) and lag-time (tlag) were estimated. The Jss and Kp show that permeation of butorphanol through olfactory mucosa is different than respiratory mucosa. Moreover, Jss for formulation 2 was higher than formulation 1 in both anatomical areas, probably for the effect of the surfactant. The present results are promising to carry on with the development of formulation of butorphanol for intranasal administration.

Application of chitosan and its derivatives in drug delivery

Drug delivery is a method of delivering drug to the patients in a way which increases the concentration of drug to the relevant site by directing the drug to the specific site of action. Polymeric drug delivery systems are mostly preferred to take the drug to the specific site of action and achieve the therapeutic effect. Among different types of biocompatible polymers, carbohydrate-based polymers or polysaccharides are the most common natural polymers with complex structures consisting of long chains of monosaccharide or disaccharide units bound by glycosidic linkages. One such polymer is chitosan which is used in drug delivery. Chitosan’s appealing properties, especially of natural origin, may mediate the protection against degradation of the biologically active substance, control the release of the drug, boost the absorption, increase the physiological action and result in a consequent reduction in the rate of administration. Another advantage of using chitosan is its chemical structure that could be modified easily which makes chitosan derivatives used for different applications. The main objective is to provide an overview on chitosan and its derivatives applications in drug delivery.

Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila

The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.

Nano-Hydroxyapatite Gel and Its Effects on Remineralization of Artificial Carious Lesions

Introduction. Nano-hydroxyapatite gel (NHG) has never been investigated for enamel remineralization. This study evaluated the effects of two concentrations of NHG on remineralization of an artificial carious lesion in comparison with nano-HA toothpaste (NHT) and fluoride varnish (FV). Materials and Methods. Carious lesions were prepared on 100 enamel samples and divided into 5 groups: FV, NHT, 20% NHG, and 30% NHG. One untreated (NT) group was left as control. The hardness of the surface was evaluated before, during, and after remineralization. Microhardness at various phases and the percent recovery of hardness (%HR) were determined and analyzed with ANOVA. Polarized-light micrographs (PLM) were evaluated for depth of the carious lesion. Results. Significantly different remineralization capability was indicated for tested agents ( p < 0.05 ). NHT was significantly capable of remineralization greater than NHG, FV, and NT ( p < 0.05 ). No noticeable difference in %HR between 20% NHG and 30% NHG ( p > 0.05 ) was found. Decreasing in the depth of caries lesion was notified by PLM as applying either NHT or NHG as greater than FV, with no reduction in the depth for NT. Conclusions. Nano-HA both in toothpaste and gel form was capable of remineralization better than fluoride varnish. Comparable remineralization of 20% versus 30% NHG was evidenced. NHG for both concentrations was recommended as a capable remineralizing agent for caries remineralization. Clinical Significance: This study indicated that an application of nano-HA gel is an attractive route to deliver the material and can be more effective and less toxic than conventional formulations and provide its effectiveness directly at the site of action, especially for a noncooperative young child and medicinally intimidated patients who may face with inconvenience in using toothbrush and toothpaste for hygiene control.

Gezielte Injektion von Effektoren durch Kontrolle der Proteindynamik

The type III secretion system (T3SS) enables direct injection of bacterial effector proteins into eukaryotic cells. We found that the dynamic cytosolic interface of the system allows Yersinia enterocolitica to suppress premature secretion at low pH, ensuring rapid activation at the site of action. Exploiting this principle, we developed a light-controlled T3SS based on optogenetic interaction switches, which provides unprecedented spatiotemporal control of protein secretion and translocation.

Cationic Lipid-Based Formulations for Encapsulation and Delivery of Anti-EFG1 2’OMethylRNA Oligomer

Background: The effective protection and delivery of antisense oligomers to its site of action is a challenge without an optimal strategy. Some of the most promising approaches encompass the complexation of nucleic acids, which are anionic, with liposomes of fixed or ionizable cationic charge. Thus, the main purpose of this work was to study the complexation of cationic liposomes with anti-EFG1 2’OMe oligomers and evaluate the complex efficacy to control Candida albicans filamentation in vitro and in vivo using a Galleria mellonella model. Results: To accomplish this, cationic 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) was mixed with three different neutral lipids dioleoylphosphocholine (DOPC), dioleoylphosphatidylethanolamine (DOPE) and monoolein (MO) and used as delivery vectors. Fluorescence Cross Correlation Spectroscopy measurements revealed a high association between antisense oligomers (ASO) and cationic liposomes confirming the formation of lipoplexes. In vitro, all cationic liposome-ASO complexes were able to release the anti-EFG1 2’OMe oligomers and consequently inhibit C. albicans filamentation up to 60 % after 72 h. In vivo, from all formulations the DOTAP/DOPC 80/20 ρchg=3 formulation proved to be the most effective, enhancing the G. mellonella survival by 40% within 48 h and by 25% after 72 h of infection.Conclusions: In this sense, our findings show that DOTAP-based lipoplexes are very good candidates for nano-carriers of anti-EFG1 2’OMe oligomers.

Pseudohypoparathyroidism-Ib due to novel heterozygous stop gain mutation in exon 8 of STX16 gene: A case report

We report a case of pseudohypoparathyroidism type 1b (PHP1b) manifesting in childhood with hypocalcemic seizures. Symptomatic hypocalcemia is a common emergency in the pediatric age group with vitamin D deficiency being a frequent underlying etiology and PHP is rare. Patients with PHP1b do not depict the Albright’s hereditary osteodystrophy (AHO) phenotype typical of patients with PHP1a and pseudopseudohypoparathyroidism (PPHP). The resistance to parathyroid hormone (PTH) is documented mostly at renal tubular site of action in patients with PHP1b. Hypothyroidism is reported occasionally, signifying resistance to thyroid-stimulating hormone (TSH). Individuals with autosomal dominant and maternally inherited form of PHP harbor methylation defects at GNAS exon A/B, while sporadic and non-familial cases harbor methylation defects at other locus sites, including differentially methylated regions (GNAS-DMR). A novel heterozygous stop gain mutation c.C910T/p.Arg304X in exon 8 of the STX16 gene (Syntaxin 16) was observed in our case. Resistance seems limited to the renal action of PTH alone as currently, TSH level is normal. Maternal STX16 gene analysis results confirmed the modality of inheritance.