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1.
Virusdisease ; 30(3): 336-343, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31803799

RESUMEN

Influenza A viruses are highly adaptable and are the main pathogen behind winter time morbidity. The present study reports the molecular and phylogenetic characterization of A(H1N1)pdm09 and H3N2 isolates from Haryana, India during 2015 influenza outbreak. A total of 144 nasopharyngeal samples were collected from Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India form September 2014 to February 2016. The samples were screened for influenza A subtypes; A(H1N1)pdm09 and H3N2 by using real-time RT-PCR. Virus isolation and hemagglutinin gene sequencing studies were performed for selected positive samples. Out of 24 (16.6%) Influenza A positive samples, 13 (54.2%) and 11 (45.8%) were subtyped into A(H1N1)pdm09 and H3N2, respectively by real-time RT-PCR. Genetic analysis of A(H1N1)pdm09 isolates revealed the presence of key mutations (P100S, S202T and S220T) in HA gene as compare to reference strain A/California/07/2009 and these isolates were grouped in clade 6B.1 and 6B.2. All A(H3N2) isolates were clustered in clade 3C.2a and revealed specific amino acid substitutions of N161S and P214S in their HA genes in comparison to the reference strain A/Texas/50/2012. The HA gene sequences of all isolates showed 97-98% of nucleotide sequence similarity with their respective reference strains. Influenza A(H1N1)pdm09 and H3N2 isolates were drifted significantly from their respective vaccines strains of 2015-2016 and were more closely related to recommended vaccine strains for flu season 2017-2018. The study supports the need of routine influenza surveillance and continuous monitoring of the genetic changes in the major antigenic sites of these viruses.

2.
Ann Clin Microbiol Antimicrob ; 18(1): 42, 2019 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-31847837

RESUMEN

BACKGROUND: Urinary tract infection (UTI) is one of the frequently diagnosed infectious diseases which is caused mainly by Escherichia coli. E. coli confers resistance against the two major classes of antibiotics due to the production of extended spectrum ß-lactamase enzymes (ESBL), biofilm, etc. Biofilm produced by uropathogenic E. coli (UPEC) protects from host immune system and prevent entry of antimicrobial compounds. The main objective of this cross-sectional study was to determine the correlation of biofilm production and antibiotic resistance as well as to characterize the pgaA and pgaC genes responsible for biofilm formation among uropathogenic ESBL producing E. coli. METHODS: A total of 1977 mid-stream urine samples were examined and cultured for bacterial strain identification. ESBL was detected by combined disc method following CLSI whereas biofilm formation was analyzed by semi-quantitative method. Furthermore, the pgaA and pgaC genes responsible for biofilm formation in UPEC were detected by multiplex PCR. All the statistical analyses were done via IBM SPSS Statistics 21 where Pearson's correlation test were used to determine correlation (-1 ≥ r ≤ 1). RESULTS: E. coli was the predominant causative agent, which accounted 159 (59.3%) of the Gram-negative bacteria, where 81 (50.9%) E. coli strains were found to be ESBL producers. In addition, 86 (54.1%) E. coli strains were found to be biofilm producers. Both the pgaA and pgaC genes were detected in 45 (93.7%) the UPEC isolates, which were both biofilm and ESBL producers. Moreover, there was a positive correlation between biofilm and ESBL production. CONCLUSION: The analyses presented weak positive correlation between biofilm and ESBL production in which biofilm producing UPEC harbors both pgaA and pgaC genes responsible for biofilm formation.

3.
Can J Microbiol ; : 1-12, 2019 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-31682478

RESUMEN

Zika virus (ZIKV) is a mosquito-borne virus that was first isolated from Zika forest, Uganda, in 1947. Since its inception, major and minor outbreaks have been documented from several parts of world. Aedes spp. mosquitoes are the primary vectors of ZIKV, but the virus can also be transmitted through sexual practices, materno-fetal transmission, and blood transfusion. The clinical presentations of symptomatic ZIKV infections are similar to dengue and chikungunya, including fever, headache, arthralgia, retro-orbital pain, conjunctivitis, and rash. ZIKV often causes mild illness in the majority of cases, but in some instances, it is linked with congenital microcephaly and autoimmune disorders like Guillain-Barré syndrome. The recent Indian ZIKV outbreak suggests that the virus is circulating in the South East Asian region and may cause new outbreaks in future. At present, no specific vaccines or antivirals are available to treat ZIKV, so management and control of ZIKV infections rely mostly on preventive measures.

5.
J Exp Bot ; 2019 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-31624829

RESUMEN

Potassium (K+) is an essential cation in all organisms that influences crop production and ecosystem stability. Although, most soils are rich in K minerals, relatively little K+ is present in forms that are available to plants. Moreover, leaching and runoff from the upper soil layers contribute to K+ deficiencies in agricultural soils. Hence, the demand for K fertilizer is increasing worldwide.  K+ regulates multiple processes in cells and organs, K+ deficiency resulting in decreased plant growth and productivity. Here, we discuss the complexity of ROS-calcium-hormone signalling network that is responsible for the sensing of K+ deficiency in plants, together with genetic approaches using K+ transporters that have been used to increase K+-use-efficiency (KUE) in plants, particularly under environmental stress conditions such as salinity and heavy metal contamination. Publicly available rice transcriptome data is used to demonstrate the two-way relationship between K+ and nitrogen nutrition, highlighting how each nutrient can regulate the uptake and root-to-shoot translocation of the other. Future research directions are discussed in terms of this relationship, as well as prospects for molecular approaches for the generation of improved varieties and the implementation of new agronomic practices. An increased knowledge of the systems that sense and take up K+, and their regulation, will not only improve current understanding of plant K+ homeostasis but also facilitate new research and the implementation of measures to improve plant KUE for sustainable food production.

6.
Indian J Med Res ; 149(6): 778-782, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31496531

RESUMEN

Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE. Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy. Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two. Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.

7.
Bioprocess Biosyst Eng ; 42(10): 1681-1693, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31286218

RESUMEN

The genes for dextransucrase and dextranase were cloned from the genomic regions of Leuconostoc mesenteroides MTCC 10508 and Streptococcus mutans MTCC 497, respectively. Heterologous expression of genes was performed in Escherichia coli. The purified enzyme fractions were entrapped in the alginate-pectin beads. A high immobilization yield of dextransucrase (~ 96%), and dextranase (~ 85%) was achieved. Alginate-pectin immobilization did not affect the optimum temperature and pH of the enzymes; rather, the thermal tolerance and storage stability of the enzymes was improved. The repetitive batch experiments suggested substantially good operational stability of the co-immobilized enzyme system. The synergistic catalytic reactions of alginate-pectin co-entrapped enzyme system were able to produce 7-10 g L-1 oligosaccharides of a high degree of polymerization (DP 3-9) from sucrose (~ 20 g L-1) containing feedstocks, e.g., table sugar and cane molasses. The alginate-pectin-based co-immobilized enzyme system is a useful catalytic tool to bioprocess the agro-industrial bio-resource for the production of prebiotic biomolecules.

8.
J Nepal Health Res Counc ; 16(41): 434-437, 2019 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-30739936

RESUMEN

BACKGROUND: Dermatophytosis are the most common types of cutaneous fungal infection seen in human and animals affecting skin, hair and nails caused by dermatophytes. The diagnosis of dermatophytes is based on the clinical observation and laboratory diagnosis by direct microscopic examination and fungal cultures. The present study is undertaken to isolate different type of dermatophytes causing fungal infection. METHODS: A prospective cross-sectional study design was used in a total of 90 clinically suspected cases of dermatophytic infection attending the out patient department of Kathmandu Medical College and Teaching hospital (KMCTH). Skin scraping, hair and nail samples were collected from the patients and were processed by direct microscopy and culture using standard protocol. Dermatophytes were identified based on the microscopic arrangement of microconidia and macroconidia. RESULTS: Dermatophytosis was more common in the age group of 21-40 years and was more predominant among male with male to female ratio of 1.7: 1. Among the total clinically suspected cases of dermatophytosis, 53 were positive in direct microscopy and only a total of 20 were positive by culture. Most common clinical type observed in our study was Tinea corporis(25%) followed by Tinea cruris. Trichophyton rubrum(50%) was the commonest aetiological agent in majority of clinical types followed by Trychophyton mentagrophytes(35%). CONCLUSIONS: The study highlighted T. corporis followed by T. cruris and T. unguim as the most common clinical pattern of dermatophytosis with a male predominance and 21-40 years being the most affected age group. T. rubram was the most common aetiological agent causing dermatophytosis.


Asunto(s)
Arthrodermataceae , Dermatomicosis/microbiología , Enfermedades del Cabello/microbiología , Onicomicosis/microbiología , Adulto , Animales , Arthrodermataceae/aislamiento & purificación , Estudios Transversales , Femenino , Cabello/microbiología , Humanos , Masculino , Persona de Mediana Edad , Uñas/microbiología , Nepal/epidemiología , Servicio Ambulatorio en Hospital , Estudios Prospectivos , Piel/microbiología , Taenia/aislamiento & purificación , Trichophyton/aislamiento & purificación , Adulto Joven
9.
Eur J Pharm Biopharm ; 136: 48-69, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30633972

RESUMEN

Transdermal drug delivery offers several attractive advantages over the traditional oral and parenteral routes. Particularly, in case of paediatric patients, it helps to overcome the issues specific to this population, such as difficulty in swallowing and palatability of oral medicines as well as fear and pain associated with needles. However, due to the formidable barrier characteristic of the stratum corneum, it fails in the effective systemic delivery of broad range of therapeutic molecules, especially macromolecules and genetic material. Over the last two decades, microneedle technology has been portrayed as a strategy to infringe the stratum corneum, in a minimally invasive manner, and enable the successful passage of molecules by creating transient channels across the skin. There has been an exponential surge in the number of studies exploring the design, development and fabrication of microneedles. This article reviews the evolution of microneedle technology and provides a comprehensive summary of microneedle research to date. It provides a detailed overview of the microneedle types, advanced fabrication strategies including the biodegradability and compatibility of the new materials used in fabrication. Research on microneedle-mediated paediatric drug delivery as well as insights on the application of this novel technology has been discussed. The up-to-date progress in clinical translation of microneedles and the regulatory requirements for their commercialization are highlighted along with a brief perspective on the future prospects of microneedle-mediated paediatric drug delivery. This review proposes that advanced research can further contribute to the improved therapeutic efficiency of microneedle-based delivery of numerous molecules, which are otherwise difficult to administer via the conventional transdermal delivery mechanisms.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Microinyecciones/métodos , Agujas , Preparaciones Farmacéuticas/administración & dosificación , Absorción Cutánea/fisiología , Administración Cutánea , Niño , Sistemas de Liberación de Medicamentos/instrumentación , Sistemas de Liberación de Medicamentos/tendencias , Humanos , Microinyecciones/instrumentación , Microinyecciones/tendencias , Agujas/tendencias , Preparaciones Farmacéuticas/metabolismo , Absorción Cutánea/efectos de los fármacos
10.
J Biol Chem ; 294(2): 559-575, 2019 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-30429220

RESUMEN

Rapid expression of critical stress response factors is a key survival strategy for diseased or stressed cells. During cell stress, translation is inhibited, and a pre-existing pool of cytoplasmic mRNA-protein complexes reversibly assembles into cytoplasmic stress granules (SGs). Gle1 is a conserved modulator of RNA-dependent DEAD-box proteins required for mRNA export, translation, and stress responses. Proper Gle1 function is critical as reflected by some human diseases such as developmental and neurodegenerative disorders and some cancers linked to gle1 mutations. However, the mechanism by which Gle1 controls SG formation is incompletely understood. Here, we show that human Gle1 is regulated by phosphorylation during heat shock stress. In HeLa cells, stress-induced Gle1 hyperphosphorylation was dynamic, primarily in the cytoplasmic pool, and followed changes in translation factors. MS analysis identified 14 phosphorylation sites in the Gle1A isoform, six of which clustered in an intrinsically disordered, low-complexity N-terminal region flanking the coil-coiled self-association domain. Of note, two mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), phosphorylated the Gle1A N-terminal domain, priming it for phosphorylation by glycogen synthase kinase 3 (GSK3). A phosphomimetic gle1A6D variant (in which six putative Ser/Thr phosphorylation sites were substituted with Asp) perturbed self-association and inhibited DEAD-box helicase 3 (X-linked) (DDX3) ATPase activity. Expression of alanine-substituted, phosphodeficient GFP-gle1A6A promoted SG assembly, whereas GFP-gle1A6D enhanced SG disassembly. We propose that MAPKs and GSK3 phosphorylate Gle1A and thereby coordinate SG dynamics by altering DDX3 function.


Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Adenosina Trifosfatasas/metabolismo , Gránulos Citoplasmáticos/metabolismo , Células HeLa , Humanos , Fosforilación , ARN Mensajero/metabolismo
11.
Pharm Dev Technol ; 23(10): 953-963, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30084277

RESUMEN

The scope of Implantable Drug Delivery Systems (IDDSs) comprehends a variety of sterile therapeutic implements placed inside the body to exert a certain therapeutic action for extended duration. They are classified under different categories from pharmaceutical science and regulatory perspectives. The novelty and variety of IDDSs prevent the application of a uniform regulation for all IDDS products; therefore, sponsors face regulatory challenges to register and market their products. This review investigates pharmaceutical science literature and the United States Food and Drug Administration (US FDA) regulatory guidance to find how any IDDS is classified, regulated, and introduced in the market. The regulatory classification of any IDDS, as a 'drug', 'medical device' or a 'combination product', is the cornerstone in determining the regulatory pathway, which decides the quality control requirements preceding the marketing approval. IDDSs are generally recognized as combination products as they consist of two or more regulated components (drugs, medical devices or biological products) combined prior to use to function as a single entity. Although robust and defined US FDA regulatory pathways exist for each component independent of one another, the regulatory pathways for combination products are less formalized.


Asunto(s)
Sistemas de Liberación de Medicamentos/normas , Implantes de Medicamentos/normas , Control de Calidad , United States Food and Drug Administration/legislación & jurisprudencia , United States Food and Drug Administration/normas , Animales , Evaluación Preclínica de Medicamentos/normas , Implantes de Medicamentos/administración & dosificación , Humanos , Comercialización de los Servicios de Salud/legislación & jurisprudencia , Comercialización de los Servicios de Salud/normas , Estados Unidos
12.
Artículo en Inglés | MEDLINE | ID: mdl-30104538

RESUMEN

(1) Background: Despite the growing use of e-cigarettes, in most countries, there is no regulation covering manufacturing standards of the solution ('e-liquid'), leading to concerns over the accuracy of labelling and stability of the products under a range of conditions. Following the United States (US) Food and Drug Administration (FDA) requirements for manufacture of e-liquids, we aimed to develop a simple high-performance liquid chromatography (HPLC) method to determine nicotine content in nicotine-containing e-liquids, even in the presence of degradation products; (2) Methods: We developed an HPLC method to quantify nicotine in the presence of the two major constituents of all e-liquids, glycerine and propylene glycol, and in the presence of degradation products; (3) Results: Our HPLC method performed strongly and was validated it according to international guidelines. For the e-liquids tested, nicotine content levels were all higher than labelled (up to 117.9 ± 1.87% of the labelled content). While nicotine was shown to be unstable at 60 °C, it was stabilized at this temperature in the e-liquid formulations for up to 10 days; and (4) Conclusions: The HPLC method is suitable for adoption by laboratories to determine the actual content and stability of nicotine-containing products. The higher than labelled nicotine levels in e-liquids raises clinical and public health concerns.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Sistemas Electrónicos de Liberación de Nicotina/normas , Nicotina/análisis , Comercio/normas , Glicerol/análisis , Humanos , Etiquetado de Productos/normas , Propilenglicol/análisis , Reproducibilidad de los Resultados
13.
J Nanosci Nanotechnol ; 18(1): 623-633, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29768888

RESUMEN

Porous hydroxyapatite (HAp) nanorods using surfactant templating proceeded via microwave irradiation method. Study of BET surface area measurement of the HAp nanorods showed that surface area of HAp nanorods with a mixture of cat-anionic surfactants was higher (56.16 m2/g) than their individual counterpart (for anionic 52.8 m2/g and for cationic 48.8 m2/g) as well as without surfactant (19.07 m2/g) due to higher synergistic effect and low critical aggregation concentration of the mixture. Surfactant-directed synthesis of porous HAp has been explored in literature, but the relation between the pore size distribution, surface area and morphology and choice of surfactant(s) was not fully understood and hence in this work we have explored those parameters. The rod shape morphology and the crystal structure of the synthesized HAp nanomaterial were observed by FESEM, HRTEM, and XRD. Due to the higher surface area, HAp nanorods synthesized from the cat-anionic mixture, act as a better adsorbent for dyes and metal ions. The maximum adsorption of dye (methylene blue) was found to be 833.3 mg/g whereas for heavy metal ions like Pb2+ and Cd2+ were 909 and 714.28 mg/g respectively. The kinetic mechanism, the effects of adsorbate pH, temperature, contact time and adsorbent concentration on the dye and metal ions removal were also explored. The antibacterial property of HAp nanorods after doping with silver was investigated against the gram-negative Escherichia coli and gram-positive Bacillus subtilis bacteria by measuring minimal inhibitory concentration (MIC) method.

14.
J Pharm Sci ; 107(9): 2399-2403, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29777717

RESUMEN

Regional intraarticular delivery of local anesthetics is effective in treating postoperative pain following total knee or hip replacement. Recent research efforts have been only partially successful in achieving sustained release of the analgesic agent, in part due to limited understanding of the biological environment into which these formulations are administered. This study aimed to detail the composition and properties of postoperative periarticular fluid (PO-PAF). PO-PAF was collected from 8 patients, and the composition and physicochemical properties were determined. A number of components were identified which are lacking from phosphate buffered saline (PBS) or other synthetic media. The differences in composition led to variation in the physicochemical properties of PO-PAF compared with PBS. Notably, significantly lower surface tension (p <0.05) and higher buffer capacity (p <0.05) were observed in the biological fluid. We demonstrated that the solubility of lidocaine is almost double in PO-PAF compared to PBS (p <0.05) and that lidocaine release from a poloxamer gelling system occurred faster into PO-PAF under both sink and nonsink conditions. Collectively, these data indicate PBS is inappropriate for the in vitro evaluation of intraarticular drug delivery systems. The presented data describe that PO-PAF and will support the future development of biorelevant media to ultimately improve in vivo-in vitro correlation.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Geles/administración & dosificación , Cápsula Articular/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Composición de Medicamentos , Femenino , Geles/farmacocinética , Humanos , Inyecciones Intraarticulares , Cápsula Articular/metabolismo , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Cadera/metabolismo , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/cirugía , Dolor Postoperatorio/metabolismo
15.
Bioprocess Biosyst Eng ; 41(8): 1121-1131, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29680868

RESUMEN

The study investigated an integrated bioprocessing of raw and by-products from sugarcane and dairy industries for production of non-digestible prebiotic and functional ingredients. The low-priced feedstock, whey, molasses, table sugar, jaggery, etc., were subjected to transglucosylation reactions catalyzed by dextransucrase from Leuconostoc mesenteroides MTCC 10508. HPLC analysis approximated production of about 11-14 g L-1 trisaccharide i.e. 2-α-D-glucopyranosyl-lactose (4-galactosyl-kojibiose) from the feedstock prepared from table sugar, jaggery, cane molasses and liquid whey, containing about 30 g L-1 sucrose and lactose each. The trisaccharide was hydrolysed into the prebiotic disaccharide, kojibiose, by employing recombinant ß-galactosidase from Escherichia coli. The enzyme ß-galactosidase achieved about 90% conversion of 2-α-D-glucopyranosyl-lactose into kojibiose. The D-fructose generated by catalytic reactions of dextransucrase was targeted for catalytic transformation into rare sugar, D-allulose (or D-psicose), by treating the samples with Smt3-D-psicose 3-epimerase. The catalytic reactions resulted in the conversion of ~ 25% D-fructose to D-allulose. These bioactive compounds are known to exert a plethora of benefits to human health, and therefore, are preferred ingredients for making functional foods.


Asunto(s)
Metabolismo de los Hidratos de Carbono , Carbohidratos , Industria Lechera , Melaza/microbiología , Saccharum/metabolismo
17.
Mater Sci Eng C Mater Biol Appl ; 84: 248-253, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29519436

RESUMEN

We report the fabrication of PEDOT films using vapour phase polymerisation with Fe(III)tosylate as the oxidant and to provide the doping ion. Multiple polymerisation steps resulted in the formation of free-standing PEDOT films. The PEDOT films were highly conductive, a single layer was 1840±50S/cm with a small decrease in conductivity for the five layered films to 1550±60S/cm. The five-layered films were flexible and freestanding in air with a thickness of 1.66±0.06µm. The ability of the freestanding PEDOT films to act as electrically tuneable rate controlling membranes was determined for nicotine (MW 162.2Da), dexamethasone phosphate (MW 516.4Da) and bovine lactoferrin (MW 80kDa), using a customised Franz cell. The membranes were highly permeable to nicotine and dexamethasone phosphate, however, the large lactoferrin molecules could not diffuse through the PEDOT membranes. The permeability of dexamethasone phosphate could be controlled electrically with an increase in flux observed when the membranes were maintained in the oxidised state compared to the reduce state. This is the first report where free standing PEDOT films were prepared by vapour phase polymerisation; these films were capable of electrically modifiable permeation of small drug molecules. The free standing and highly conductive PEDOT membranes are exciting materials to explore for molecular separation and drug delivery applications.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/química , Gases/química , Membranas Artificiales , Preparaciones Farmacéuticas/metabolismo , Polímeros/química , Dexametasona/análogos & derivados , Dexametasona/química , Dexametasona/metabolismo , Conductividad Eléctrica , Técnicas Electroquímicas , Lactoferrina/química , Lactoferrina/metabolismo , Nicotina/química , Nicotina/metabolismo , Oxidación-Reducción , Permeabilidad , Preparaciones Farmacéuticas/química , Polimerizacion , Espectroscopía Infrarroja por Transformada de Fourier
18.
Drug Deliv Transl Res ; 8(3): 708-718, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29582351

RESUMEN

An understanding of biological fluids at the site of administration is important to predict the fate of drug delivery systems in vivo. Little is known about peritoneal fluid; therefore, we have investigated this biological fluid and compared it to phosphate-buffered saline, a synthetic media commonly used for in vitro evaluation of intraperitoneal drug delivery systems. Human peritoneal fluid samples were analysed for electrolyte, protein and lipid levels. In addition, physicochemical properties were measured alongside rheological parameters. Significant inter-patient variations were observed with regard to pH (p < 0.001), buffer capacity (p < 0.05), osmolality (p < 0.001) and surface tension (p < 0.05). All the investigated physicochemical properties of peritoneal fluid differed from phosphate-buffered saline (p < 0.001). Rheological examination of peritoneal fluid demonstrated non-Newtonian shear thinning behaviour and predominantly exhibited the characteristics of an entangled network. Inter-patient and inter-day variability in the viscosity of peritoneal fluid was observed. The solubility of the local anaesthetic lidocaine in peritoneal fluid was significantly higher (p < 0.05) when compared to phosphate-buffered saline. Interestingly, the dissolution rate of lidocaine was not significantly different between the synthetic and biological media. Importantly, and with relevance to intraperitoneal drug delivery systems, the sustained release of lidocaine from a thermosensitive gel formulation occurred at a significantly faster rate into peritoneal fluid. Collectively, these data demonstrate the variation between commonly used synthetic media and human peritoneal fluid. The differences in drug release rates observed illustrate the need for bio-relevant media, which ultimately would improve in vitro-in vivo correlation.


Asunto(s)
Líquido Ascítico/química , Sistemas de Liberación de Medicamentos , Cloruro de Sodio/química , Anestésicos Locales/química , Tampones (Química) , Liberación de Fármacos , Electrólitos/análisis , Geles , Humanos , Concentración de Iones de Hidrógeno , Lidocaína/química , Lípidos/análisis , Concentración Osmolar , Proteínas/análisis , Reología , Solubilidad , Propiedades de Superficie
19.
Int J Pharm ; 543(1-2): 38-45, 2018 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-29581065

RESUMEN

Conducting polymers such as polypyrrole (PPy) can be used as electrically responsive drug delivery systems typically prepared by electrochemical polymerisation, however, the amount of drug that can be delivered is typically low. To increase drug delivery capacity and prepare larger amounts of polymer, PPy nanoparticles were produced by chemical polymerisation over drug-loaded micelles. Two forms of dexamethasone were included to increase total drug loading and to explore the mechanisms of loading and release. The particles produced were approximately 50 nm in size and their conductivity and reversible redox activity were demonstrated. Loading of the hydrophobic dexamethasone base was more efficient than for the more hydrophilic phosphate salt. After pressing the particles into the desired form, electrically-responsive drug release was achieved with a pulsed potential signal being the most effective way to trigger release. Notably, the anionic phosphate salt of the drug was more sensitive to electrically stimulated release than the uncharged base of dexamethasone, highlighting the role of electrostatic forces in driving drug release. This system has potential to be loaded with different drugs widening the scope of application of these smart particles to treat a range of disease states.


Asunto(s)
Dexametasona/análogos & derivados , Portadores de Fármacos/química , Glucocorticoides/química , Micelas , Polímeros/química , Pirroles/química , Bencenosulfonatos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Dexametasona/administración & dosificación , Dexametasona/química , Liberación de Fármacos , Técnicas Electroquímicas , Electroquímica , Glucocorticoides/administración & dosificación , Humanos , Polimerizacion , Polímeros/administración & dosificación , Pirroles/administración & dosificación , Epitelio Pigmentado de la Retina/citología , Tensoactivos/química
20.
Drug Deliv Transl Res ; 8(3): 820-829, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29411295

RESUMEN

Sustained lidocaine release via a thermoresponsive poloxamer-based in situ gelling system has the potential to alleviate pain following knee arthroplasty. A previously developed formulation showed a promising drug release profile in synthetic phosphate-buffered saline (PBS). To support the translation of this formulation, ex vivo characterisation was warranted. This study therefore aimed (1) to modify the previously developed formulation to reduce the burst release, (2) to compare the release behaviour into ex vivo human intra-articular fluid (IAF) and PBS and (3) to determine the formulation spread in an ex vivo human knee using magnetic resonance imaging (MRI). All formulations provided sustained release out to 72 h; polyvinyl pyrrolidone was the most effective additive yielding a small yet significant decrease (p < 0.05) in the burst release. Release of lidocaine from the formulation occurred significantly faster into IAF compared to PBS (1.4 times greater release in the first 24 h), correlating with faster rates of gel erosion in IAF. Injection was easily achieved through a 21-gauge (G) needle into the synovial space of a human cadaveric knee, and MRI scans revealed effective spreading of the formulation throughout the joint cavity. The pattern of spread is promising for the drug to reach the widespread nerve endings in the joint capsule; the effect of this spread on release in an in vivo setting will be the subject of future studies. The demonstrated properties indicate that the in situ gelling formulation has the potential to be used clinically to treat post-operative pain following knee arthroplasty.


Asunto(s)
Anestésicos Locales/administración & dosificación , Lidocaína/administración & dosificación , Poloxámero/administración & dosificación , Povidona/administración & dosificación , Anestésicos Locales/química , Artroplastia de Reemplazo de Rodilla , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Liberación de Fármacos , Geles , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/metabolismo , Lidocaína/química , Imagen por Resonancia Magnética , Poloxámero/química , Povidona/química , Temperatura Ambiental
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