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Selected polysaccharides at comparison for their mucoadhesiveness and effect on the precorneal clearance of different drugs in the rabbit model
No full textMucoadhesive polysaccharides may prolong the residence of ophthalmic drugs in precorneal area. In this article, the mucoadhesiveness of arabinogalactan, tamarind seed polysaccharide, hyaluronan, hydroxyethylcellulose is compared in vivo, by the polymer residence time in rabbit tear fluid, and in vitro, by the polymer-induced increase of viscosity of a mucin dispersion. Polymer residence is prolonged by increased viscosity but shortened by reflex tearing caused by excessive viscosity. Tamarind seed polysaccharide is the most effective in prolonging the residence of ketotifen and diclofenac in precorneal area; hence, it is the optimal eyedrop additive as it is mucoadhesive while not increasing viscosity excessively
Effect of N-trimethylchitosan on transcellular and paracellular transcorneal drug trasport
No full textThe effects of N-trimethylchitosan (TMC) on the transcorneal transport of dexamethasone, taken as a marker of the transcellular penetration route, and of tobramycin, a marker of the paracellular route, were studied by assessing the TMC effect on the intraocular pharmacokinetics of each marker. The drugs were topically applied via erodible inserts (weight, 20 mg; diameter, 6 mm; drug dose, 0.3 mg) based on poly(ethylene oxide), containing 10% w/w medicated TMC microspheres (diameter <2.5 μm). Before application, drug release and insert erosion kinetics, and release mechanism were studied in vitro. With either drug, introduction of 10% TMC into insert did not substantially alter the release and erosion rates, hence this formulation was apt to isolate the transcorneal penetration enhancing effect of TMC. Ocular pharmacokinetics were determined in the rabbit model. TMC produced significant increases of dexamethasone Cmax (5.69 ± 0.49 vs. 3.07 ± 0.31 μg/ml) and AUC (619.3 ± 32.5 vs. 380.5 ± 32.0 μg min/ml) in the aqueous with respect to the reference TMC-free insert. On the other hand, TMC was unable to yield tobramycin concentrations in the aqueous exceeding the determination limit (0.5 μg/ml). In conclusion, TMC enhances transcorneal transport via the transcellular route, whereas it is unable to effectively open the tight junctions between corneal cells
Polymeric enhancers of mucosal epithelia permeability: synthesis, transepithelial penetration-enhancing properties, mechanism of action, safety issues
No full textTransmucosal drug administration across nasal, buccal, and ocular mucosae is noninvasive, eliminates hepatic first-pass metabolism and harsh environmental conditions, allows rapid onset, and further, mucosal surfaces are readily accessible. Generally, however, hydrophilic drugs, such as peptides and proteins, are poorly permeable across the epithelium, which results in insufficient bioavailability. Therefore, reversible modifications of epithelial barrier structure by permeation enhancers are required. Low molecular weight enhancers generally have physicochemical characteristics favoring their own absorption, whereas polymeric enhancers are not absorbed, and this minimizes the risk of systemic toxicity. The above considerations have warranted the present survey of the studies on polymeric transmucosal penetration-enhancers that have appeared in the literature during the last decade. Studies on intestinal permeation enhancers are also reviewed as they give information on the mechanism of action and safety of polymers. The synthesis and characterization of polymers, their effectiveness in enhancing the absorption of different drugs across different epithelium types, their mechanism of action and structure-efficacy relationship, and the relevant safety issues are reviewed. The active polymers are classified into: polycations (chitosan and its quaternary ammonium derivatives, poly-L-arginine (poly-L-Arg), aminated gelatin), polyanions (N-carboxymethyl chitosan, poly(acrylic acid)), and thiolated polymers (car-boxymethyl cellulose-cysteine, polycarbophil (PCP)-cysteine, chitosan-thiobutylami-dine, chitosan-thioglycolic acid, chitosan-glutathione conjugates)
Synthesis, characterization and evaluation of thiolated quaternary ammonium-chitosan conjugates for enhanced intestinal drug permeation
No full textn a previous report quaternary ammonium-chitosan conjugates (N+-Chs) endowed with intestinal drug permeability-enhancing properties were described. They are characterized by short pendant chains of n adjacent diethyl-dimethylene-ammonium groups substituted onto the primary amino group of the chitosan (Ch) repeating units. In the present work two N+-Chs, one having DS (degree of substitution) = 59.2 ± 4.5%, n = 1.7 ± 0.1 (N+(60)-Ch), the other one having DS = 40.6 ± 1.3%, n = 3.0 ± 0.2 (N+(40)-Ch) were used to synthesize novel multifunctional non-cytotoxic Ch derivatives, each carrying thiol along with quaternary ammonium groups (N+-Ch-SH), with increased potential to enhance transepithelial drug transport. They have been obtained by transforming the residual free amino groups of N+(60)-Ch and N+(40)-Ch into 3-mercaptopropionamide moieties. The former yielded 4.5 ± 0.7% thiol-bearing groups, the latter, 5.2 ± 1.1% of such groups, on a Ch repeating unit basis. The multifunctional derivatives have improved the ability of the parent N+-Chs to enhance the permeability of the water-soluble macromolecular fluorescein isothiocyanate dextran, MW 4400 Da (FD4) and that of the lipophilic dexamethasone (DMS) across the excised rat intestinal mucosa and Caco-2 cell monolayer, respectively. The data from the present work altogether point to a synergism of quaternary ammonium and thiol groups to improve the intestinal drug absorption enhancing properties of the multifunctional Ch derivatives
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Improved synthesis of quaternary ammonium-chitosan conjugates (N+-Ch) for enhanced intestinal drug permeation
No full textThe pH-induced structural modifications of the reaction product between chitosan and 2-diethylaminoethyl chloride are studied with the purpose of testing and comparing the resulting chitosan derivatives on the basis of their intestinal drug permeability-enhancing properties. The reaction reproducibly yielded conjugates comprising short pendant chains of n adjacent diethyl-dimethylene-ammonium groups substituted onto the primary amino group of the chitosan repeating unit. The more significant derivatives, N+-Ch-7 (degree of substitution, DS = 41%; n = 3) and N+-Ch-8 (DS = 59%; n = 1.7) were prepared at pH 7 and 8, respectively. The apparent permeability (Papp) of excised rat intestine was determined by means of Ussing type chambers. The hydrophilic fluorescein sodium (NaFlu) and fluorescein isothiocyanate dextran (MW 4400 Da) (FD-4), and the lipophilic rhodamine 123 (Rh-123), were applied in Ringer buffer to the apical side. Apical to basolateral transport was measured in the absence or presence of 0.5% (w/v) of the polymer under test. N+-Ch-7 and N+-Ch-8 were more effective Papp enhancers than N-trimethyl-chitosan. Both N+-Ch-7 and N+-Ch-8 enhanced the Papp of NaFlu (enhancement ratio, ER = 1.84 and 1.33, respectively), while N+-Ch-8 was the more effective enhancer for FD-4 (ER = 2.14). The Papp of Rh-123 was significantly enhanced only by N+-Ch-7 (ER = 1.37). Permeant-polymer binding counteracted the enhancement effect of polymer on transmembrane permeant flux. Contact with the chitosan conjugates did not impair the mucosal epithelium integrity
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
A Novel polyelectrolyte complex (PEC) Hydrogel for controlled drug delivery to the colon
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