1,721,054 research outputs found
Encapsulation of all-trans-retinoic acid in polymeric micelles
No full textAll-trans-retinoic acid (ATRA) is being increasingly included in antitumor therapeutical schemes for the treatment of various type of tumors; however the difficulty of increasing plasma concentrations of ATRA in vivo hindered, until now, a correct evaluation of its possible pro-apoptotic effect towards both the proliferating and non proliferating neuroblastic cells.
Recent approaches to enhance the solubility of hydrophobic drugs considered polymeric micelles particularly interesting for their efficiency in trapping lipophilic drugs within their internal core, the possibility to provide small and flexible structures able to easily extravasate in the solid tumor and a propensity to evade scavenging by the mononuclear phagocyte system. Our studies focus on micelles prepared from a water soluble polymer, PVA, conjugated with lipid alkyl chains, thus achieving amphiphilicity, such as that of A-B type block co-polymers. The core of the polymer serves as a non-aqueous reservoir, where the drug is entrapped, but also stabilized against chemical modifications by the physiological environment [1].
All-trans-retinoic acid (ATRA) is now included in many anti-tumour therapeutic schemes. Unfortunately its poor aqueous solubility hampers its parenteral formulation. To date, there is no parenteral formulation of ATRA commercially available, while oral administration of ATRA is associated with progressively diminishing ATRA levels in plasma. An ATRA formulation, obtained by complexation of the drug into polymeric micelles, might be suitable for parenteral administration overcoming these unwanted effects [2]. To this purpose we prepared an amphiphilic polymer by poly-vinylalcohol (PVA) substitution with oleyl amine at 1.5% substitution degree and evaluated its functional properties with regard to ATRA complexation.
EXPERIMENTAL PART
The new amphiphile polymer, PVA-co-oleyl-vinyl carbamate, obtained by PVA partial substitution with oleylamine, contains a carbamate bond, rather than an ester bond, as a spacer between the hydrophilic PVA and the hydrophobic oleyl chains. The polymer thus obtained holds enhanced aqueous solubility in the presence of enhanced substitution degree. The solubilizing ability of the substituted polymer was evaluated towards ATRA in aqueous solutions of the polymer and of drug–polymer mixtures obtained by spray-drying hydro-alcoholic solutions of ATRA and polymer at 1:3, 1:5 and 1:10 drug–polymer weight ratios.
RESULTS AND DISCUSSION
The spray-dried complexes rapidly dissolve in water, providing high levels of ATRA solubilization as a function of the drug–polymer weight ratio. The complexes characterized by 1:5 drug–polymer weight ratio (▲) provided higher levels of ATRA solubilization than 1:3 (▄) and 1:10 (▬) drug–polymer weight ratios respectively. Pre-formed polymeric micelles in water, equilibrated in the presence of excess solid ATRA, provided lower levels of solubilization (●). The drug release from the complexes was very slow in PBS, indicating their suitability in anti-tumour drug targeting, where a fundamental requirement is stability towards drug release for at least 24 h, corresponding to the average circulation time period of macromolecular carriers.
A comparison between the present polymer, containing a polyvinyl backbone linked to oleyl chains by carbamate bonds and a previously studied polymer, based on the same polyvinyl backbone linked to oleyl chains by ester bonds, indicates that the nature of the bond between the main backbone and the oleyl chains strongly influence the physico-chemical characteristics of the final polymer. In the presence of the ester bond the highest polymer aqueous solubility obtained was 30 mg/ml at 37°C at a substitution degree not exceeding 1%. The increase in the substitution degree decreased the polymer solubility.
In the presence of the carbamate bond it was possible to increase both the substitution degree and the aqueous pol..
Ex-vivo and in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base
No full textThe aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichia coli and Staphylococcus aureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system
Modified polyvinylalcohol for encapsulation of all-trans-retinoic acid in polymeric micelles.
No full textAll-trans-retinoic acid (ATRA) is now included in many antitumor therapeutic schemes for the treatment of acute promyelocytic leukaemia, Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer and neuroblastoma. Unfortunately its poor aqueous solubility hampers its parenteral formulation. To date, there is no parenteral formulation of ATRA commercially available and oral administration of ATRA is associated with progressively diminishing ATRA levels in plasma, which is related to induction of retinoic acid-binding protein and increased drug catabolism by cytochrome P-450-mediated reaction. An ATRA formulation, obtained by complexation of the drug into polymeric micelles, might be suitable for parenteral administration overcoming these unwanted effects. To this purpose we prepared an amphiphilic polymer by polyvinylalcohol (PVA) substitution with oleyl amine at 1.5% substitution degree (mol substituent per 100 mol hydroxyvinylmonomer) and evaluated its functional properties with regard to ATRA complexation. The substituted polymer displayed ability to interact with ATRA both in aqueous solution and in the solid state following spray-drying of drug-polymer hydro-alcoholic solutions. The spray-dried complexes rapidly dissolved in water providing high levels of ATRA solubilization as a function of the drug-polymer weight ratio. The complexes characterized by 1:5 drug-polymer weight ratio provided higher levels of ATRA solubilization than 1:3 and 1:10 drug-polymer weight ratios respectively. Pre-formed polymeric micelles in water equilibrated in the presence of excess solid ATRA provided the lowest levels of solubilization. The drug release from the complexes was very slow in PBS, indicating their suitability in antitumor drug targeting where a fundamental requirement is stability towards drug release for at least 24 h, corresponding to the average circulation time period of macromolecular carriers. The cytotoxicity studies against neuroblastoma cell lines outlined increased cytotoxicity of complexed ATRA with respect to free ATRA, likely due to the increased bioavailability of the hydrophobic drug from the complex. We conclude that ATRA entrapped into self-assembling polymer micelles may be a useful parenteral ATRA formulation overcoming the unwanted pharmacological mechanism that lead to acquired retinoid resistance
Release of indomethacin from ultrasound dry granules containing lactose-based excipients
No full textPhysical mixtures were prepared containing indomethacin and beta-lactose and alpha-lactose-based excipients (Ludipress and Cellactose). The mixtures were compacted with the aid of ultrasound, obtaining tablets, which were milled and sieved. Granules thus obtained were examined by optical microscopy and differential scanning calorimetry. The intense yellow color of the granules and the absence of indomethacin peak in thermograms suggest important modifications of indomethacin physical state; the drug thus modified appears to be spread on the excipient particle surface as a thin film, giving a lustrous appearance. No influence of ultrasound was observed on phase transition concerning lactose; only loss of water was important under high energy ultrasound. Dissolution profiles suggest an increased release of the drug from the systems treated with ultrasound at high energy, with respect to a traditional compaction; while no difference could be evidenced among the three excipients that, however, appear all suitable for this ultrasound-aided direct compression process
Synthesis, structural characterization and antibacterial activity of novel 7-beta-{[3-(substituted phenyl)-2-propenoyl]amino}-3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins.
No full textAbstract: A series of 3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins with various 3-phenyl-2-propenoyl substituted groups at the 7-beta-position were synthesized, structurally characterized and evaluated for antibacterial activity in vitro. To prepare these derivatives by the Vilsmeier’s reagent method, it was necessary to carefully control de reaction conditions in order to avoid the formation of the biologically inactive  epimer. The NMR studies showed that the 3-phenyl-2-propenoyl moiety has little effect on chemical shifts of cephem nucleus protons and carbon atoms. Some of these cephalosporin derivatives showed good in vitro activity against methicillin sensible strains of Staphylococcus aureus (MSSA) and coagulase negative Staphylococcus (MSCoNS). Particularly effective were the compounds carrying a 3-(2’-chlorophenyl)-2-propenoyl or 2-methyl-3-phenyl-2-propenoyl moiety at 7-beta-position, booth with an antibacterial potency close to cefazoline and higher than cefuroxime. All the synthesized cephalosporins were inactive against methicillin resistant strains of Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus (MRCoNS)
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
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
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