An Investigation Of Liposomes For Oral Delivery Of A Poorly Bioavailable Model Drug: Griseofulvin

The potential of liposomal formulation as a drug delivery system for oral administration of poorly bioavailable drugs was studied using griseofulvin as the model drug. An extrusion technique using a self-assembled instrument was evaluated for nanosizing the liposomes. The particle size and size distribution of liposomes produced was affected by various processing parameters. Nevertheless, the extrusion method was simple, reproducible and more effective compared to other size-reduction methods evaluated

Photographed Rapid HIV Test Results Pilot Novel Quality Assessment and Training Schemes

HIV rapid diagnostic tests (RDTs) are now used widely in non-laboratory settings by non-laboratory-trained operators. Quality assurance programmes are essential in ensuring the quality of HIV RDT outcomes. However, there is no cost-effective means of supplying the many operators of RDTs with suitable quality assurance schemes. Therefore, it was examined whether photograph-based RDT results could be used and correctly interpreted in the non-laboratory setting. Further it was investigated if a single training session improved the interpretation skills of RDT operators. The photographs were interpreted, a 10-minute tutorial given and then a second interpretation session was held. It was established that the results could be read with accuracy. The participants (n = 75) with a range of skills interpreted results (>80% concordance with reference results) from a panel of 10 samples (three negative and seven positive) using four RDTs. Differences in accuracy of interpretation before and after the tutorial were marked in some cases. Training was more effective for improving the accurate interpretation of more complex results, e.g. results with faint test lines or for multiple test lines, and especially for improving interpretation skills of inexperienced participants. It was demonstrated that interpretation of RDTs was improved using photographed results allied to a 10-minute training session. It is anticipated that this method could be used for training but also for quality assessment of RDT operators without access to conventional quality assurance or training schemes requiring wet samples

Redundant Notch1 and Notch2 Signaling Is Necessary for IFNγ Secretion by T Helper 1 Cells During Infection with Leishmania major

The protective immune response to intracellular parasites involves in most cases the differentiation of IFNγ-secreting CD4+ T helper (Th) 1 cells. Notch receptors regulate cell differentiation during development but their implication in the polarization of peripheral CD4+ T helper 1 cells is not well understood. Of the four Notch receptors, only Notch1 (N1) and Notch2 (N2) are expressed on activated CD4+ T cells. To investigate the role of Notch in Th1 cell differentiation following parasite infection, mice with T cell-specific gene ablation of N1, N2 or both (N1N2ΔCD4Cre) were infected with the protozoan parasite Leishmania major. N1N2ΔCD4Cre mice, on the C57BL/6 L. major-resistant genetic background, developed unhealing lesions and uncontrolled parasitemia. Susceptibility correlated with impaired secretion of IFNγ by draining lymph node CD4+ T cells and increased secretion of the IL-5 and IL-13 Th2 cytokines. Mice with single inactivation of N1 or N2 in their T cells were resistant to infection and developed a protective Th1 immune response, showing that CD4+ T cell expression of N1 or N2 is redundant in driving Th1 differentiation. Furthermore, we show that Notch signaling is required for the secretion of IFNγ by Th1 cells. This effect is independent of CSL/RBP-Jκ, the major effector of Notch receptors, since L. major-infected mice with a RBP-Jκ deletion in their T cells were able to develop IFNγ-secreting Th1 cells, kill parasites and heal their lesions. Collectively, we demonstrate here a crucial role for RBP-Jκ-independent Notch signaling in the differentiation of a functional Th1 immune response following L. major infection

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Cross-talk between EZH2 and NF-kB in breast cancers.

Epigenetic changes are reported to contribute to cancer progression. EZH2 is the catalytic component of PRC2 and its SET domain is involved in histone methyltransferase activity, to silence specific genes in cancer progression. Although EZH2 SET domain independent functions have been reported recently, it still remains novel and under-characterized in the aggressive breast cancer. Correspondingly, NF-κB is constitutively active in breast cancer. As many target genes of NF-κB family of transcription factors are involved in cancer progression, inflammation and tumorigenesis, it remains unknown if EZH2 plays a role in activating some of the target genes by modulating NF-κB activity. In this study, MDA-MB231 and BT549 aggressive breast carcinoma cell lines were used to investigate the functional interaction between EZH2 and NF-κB and it was found that EZH2 physically interacts with RelB to maintain stability of the latter. Over-expression of EZH2 WT and EZH2 SET∆ increases the relative mRNA expression of TNFα, suggesting that EZH2 is required to interact with RelB in a SET domain independent way to induce transcriptional activation of TNFα. Over-expression of EZH2 in aggressive breast cancer might therefore set up a vicious cycle by increasing TNFα-induced NF-κB activation and ultimately the transcription of target genes involved in inflammation and tumorigenesis.Bachelor of Science in Biological Science

Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation

Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32%) and F2(98%)], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm), MS (357 nm) and NS (813 nm)], but with essentially similar encapsulation efficiencies (about 93%). Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1) compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2), compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm) did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation

An evaluation of the product containing Peria Katak (Momordica charantia)

The efficacy and safety of Momordica charantia based on relevant studies and reviews are described. M. charantia also known as bitter melon has been proposed to exert effects in lowering blood glucose levels by means of various forms and extracts from the plant. Over the years, commercially available preparations containing bitter melon are made available in the market despite limitations on available clinical trials. Clinical trial conducted demonstrates variety in findings on the effect of M. charantia on glycemic control with mostly not exhibiting statistically significant differences. Monitoring is vital in view of the reported side effects and precaution warranted for the specific individuals and unknown herbal-drug or herbal-food interaction that could possibly interrupt the overall management plan. For the meantime, findings generated from the studies only provide implication on the potential advantages that M. charantia offers in preventing and managing type 2 diabetes as well as the microvascular complications instead of a certain conclusion

Evaluation of Extrusion Technique for Nanosizing Liposomes

The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS), sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity, reproducible for various in vivo applications