Development and Characterization of Fexofenadine Hydrochloride Oil Entrapped Floating Alginate Beads to Enhance Oral Bioavailability

Oil entrapped floating calcium alginate beads of fexofenadine Hydrochloride were successfully prepared using sodium alginate as polymer and two different oil phases of mineral oil and olive oil by emulsion gelation method. * The FT-IR spectra of final optimized formulation confirms no drugpolymer incompatibility. * The floating time of beads was found to be more than 12 hrs suggesting that the method used for prepration was effective. The floating time of optimized formulation was within 6 minutes and floating time significantly increased as the amount of oil was increased in each formulation. * The mean particle size of beads was in range from (1.204mm to 2.0072mm) depending upon the type of polymer used. The particle size increased significantly as the amount of polymer was increased in each preparation. * The %Entrapment efficiency of beads ranging from 41.14%-85.79% increased in concentration of polymer leads to increase in entrapment efficiency. * The best formulation of oil entrapped floating calcium alginate beads of fexofenadine hydrochloride for mineral oil was found to be F5 98.03% and for Olive oil oil was found to be F7 96.7 %, drug release in 12 hrs. * The release kinetics of the optimized fexofenadine hydrochloride loaded oil entrapped beads showed that it follows Higuchi release kinetics. The release of the drug from the dosage form is carried out by diffusion and follows Korsmeyer peppas kinetics and the n value is greater than 0.5 indicating non-Fickian release. * The floating beads have been employed to make a sustained release of the drug in the stomach to enhance bioavailability and to decrease dose dumping and hence overcome its side effects. * The developed formulation shows an alternative to the conventional dosage form for the treatment of Fexofenadine hydrochloride, a nonsedating antihistamine H1 blocker used for seasonal allergic rhinitis and chronic idiopathic urticaria has limited absorption in the upper small intestine with poor oral bioavailability. * Hence, finally it was concluded that the prepared oil entrapped floating sodium alginate beads of fexofenadine may prove to be potential candidate for safe and effective sustained drug delivery over an extended period of time which can reduce dosing frequency and improved oral bioavailability

Apolipoprotein M attenuates anthracycline cardiotoxicity and lysosomal injury

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling B

Positional identification of variants of Adamts16 linked to inherited hypertension

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.6 kb region contained only two genes, LOC306664 and LOC306665. LOC306664 is predicted to translate into A Disintegrin-like and Metalloproteinase with Thrombospondin Motifs-16 (Adamts16). LOC306665 is a novel gene. All predicted exons of both LOC306664 and LOC306665 were sequenced. Non-synonymous variants were identified in only one of these genes, LOC306664. These variants were naturally existing polymorphisms among inbred, outbred and wild rats. The full-length rat transcript of Adamts16 was detected in multiple tissues. Similar to ADAMTS16 in humans, expression of Adamts16 was prominent in the kidney. Renal transcriptome analysis suggested that a network of genes related to BP was differential between congenic and S rats. These genes were also differentially expressed between kidney cell lines with or without knock-down of Adamts16. Adamts16 is conserved between rats and humans. It is a candidate gene within the homologous region on human Chromosome 5, which is linked to systolic and diastolic BP in the Quebec Family Study. Multiple variants, including an Ala to Pro variant in codon 90 (rs2086310) of human ADAMTS16, were associated with human resting systolic BP (SBP). Replication study in GenNet confirmed the association of two variants of ADAMTS16 with SBP, including rs2086310. Overall, our report represents a high resolution positional cloning and translational study for Adamts16 as a candidate gene controlling BP

Design of bio-nanosystems for oral delivery of functional compounds

Nanotechnology has been referred to as one of the most interesting topics in food technology due to the potentialities of its use by food industry. This calls for studying the behavior of nanosystems as carriers of biological and functional compounds aiming at their utilization for delivery, controlled release and protection of such compounds during food processing and oral ingestion. This review highlights the principles of design and production of bio-nanosystems for oral delivery and their behavior within the human gastrointestinal (GI) tract, while providing an insight into the application of reverse engineering approach to the design of those bio-nanosystems. Nanocapsules, nanohydrogels, lipid-based and multilayer nanosystems are discussed (in terms of their main ingredients, production techniques, predominant forces and properties) and some examples of possible food applications are given. Phenomena occurring in in vitro digestion models are presented, mainly using examples related to the utilization of lipid-based nanosystems and their physicochemical behavior throughout the GI tract. Furthermore, it is shown how a reverse engineering approach, through two main steps, can be used to design bio-nanosystems for food applications, and finally a last section is presented to discuss future trends and consumer perception on food nanotechnology.Miguel A. Cerqueira, Ana C. Pinheiro, Helder D. Silva, Philippe E. Ramos, Ana I. Bourbon, Oscar L. Ramos (SFRH/BPD/72753/2010, SFRH/BD/48120/2008, SFRH/BD/81288/2011, SFRH/BD/80800/2011, SFRH/BD/73178/2010 and SFRH/BPD/80766/2011, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE Portugal). Maria L. Flores-Lopez thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support (CONACYT Grant number: 215499/310847). The support of EU Cost Actions FA0904 and FA1001 is gratefully acknowledged