Microemulsions: a potential drug delivery system

Microemulsions are clear, transparent, thermodynamically stable dispersions of oil and water, stabilised by an interfacial film of surfactant frequently in combination with a co-surfactant. Recently, there has been a considerable interest for the microemulsion formulation, for the delivery of hydrophilic as well as lipophilic drug as drug carriers because of its improved drug solubilisation capacity, long shelf life, easy of preparation and improvement of bioavailability. In this present review, we discuss about the various advantages of microemulsion in pharmaceuticals, along with its composition variables, physicochemical characterisation etc. The potential use of microemulsion for therapeutic application is also discussed.     

Highly selective cyclic peptide ligands for NeutrAvidin and avidin identified by phage display

Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage-display selections, biotinylated macromolecular targets are often immobilized on avidin- and streptavidin-functionalized supports. Thus, the characterization of peptides that bind avidin and streptavidin is necessary for accurate interpretation of screening and selection results. Toward this goal, we panned a phage-displayed cyclic peptide library against NeutrAvidin, a chemically deglycosylated version of avidin. The selection produced a highly homologous consensus motif (Asp-Arg/Leu-Ala-Ser/Thr-Pro-Tyr/Trp). Two of these cyclic peptides, CDRATPYC and CDRASPYC, bound both NeutrAvidin and avidin with low-micromolar dissociation constants, whereas their acyclic counterparts had negligible affinity (< 80-fold). Moreover, these cyclic peptides were very specific for their targets and did not bind the structurally and functionally similar protein, streptavidin. Thus, we have identified a new class of cyclic peptides, distinct from the much-studied streptavidin-binding His-Pro-Gln peptide motif. These results will not only allow for discriminating between desired and background cyclic peptide motifs in selections and screens but also provide a new protein/peptide model system and a useful reagent in chemical biology that can have utility in protein immobilization, purification, and chemical tagging.     

Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells

Lung cancer is the leading cause of cancer death among both men and women. Only approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non-small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1-mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1-induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non-small cell lung tumor growth.     

Meta-analysis of vitamin D receptor polymorphisms and type 1 diabetes: a HuGE review of genetic association studies

Several polymorphisms in the vitamin D receptor (VDR) gene have been reported to be associated with the risk of developing type 1 diabetes, yet published findings have been conflicting. In this study, the authors attempted to evaluate the evidence regarding the association. They searched all relevant reports from original papers published from 1997 to December 2005. Predefined criteria were used to identify 1) case-control association studies examining the FokI (11 studies), BsmI (13 studies), ApaI (9 studies), and TaqI (7 studies) polymorphisms and 2) a few family-transmission studies with analysis of these four polymorphisms. In random-effects modeling, the 95% confidence intervals of the summary odds ratios for all four polymorphisms included 1, indicating no effect. Except for FokI, no heterogeneity was found. The 95% confidence intervals of the transmission proportions all included 0.5, indicating no effect. Thus, the authors found no evidence for an association between VDR gene polymorphisms and type 1 diabetes risk in either case-control studies or family-transmission studies. In fact, a reanalysis of previously published data (McDermott et al., Diabetologia 1997;40:971-5) indicated no evidence of an association as reported.     

Medical abortion in late second trimester--a comparative study with misoprostol through vaginal versus oral followed by vaginal route

A randomised controlled trial was conducted to compare the relative efficacies of two regimens: Misoprostol given only vaginally or orally followed by vaginal administration of the same drug, for second trimester abortion. Multiparous women with a pregnancy of 16 to 20 weeks with no contra-indications to the drug were selected. They were randomly allocated into two groups. Patients in the first group, the 'only vaginal misoprostol' group (n = 30), were given misoprostol 400 microg 6 hourly only through vaginal route up to a maximum of 4 such doses. Women in the other group, the 'oral plus vaginal misoprostol' group (n = 24), received 400 microg of the drug at intervals of 12 hours for 2 doses, followed by 400 microg 6 hourly per vaginum up to a maximum of 4 such. Ten units of oxytocin was started in all cases when os was 4 cm dilated. Complete expulsion was 83.33% with an average time of 13.28 hours in the only vaginal misoprostol group. Complete expulsion occurred in 87.5% of women receiving oral followed by vaginal misoprostol with an average time of 8.93 +/- 0.01 hours from the first vaginal dose (p<0.05). More importantly, 66.67% women in second group delivered within 10 hours of the vaginal dose. Complete expulsion was defined in those cases where no check curettage was needed. Side-effects were not significant. This implies that misoprostol given by the vaginal route following oral priming doses had a higher success rate and a potential for a reduced hospital stay and higher bed turn-over rate.