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1.
Sensors (Basel) ; 23(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37896481

RESUMO

Glaciers and snow are critical components of the hydrological cycle in the Himalayan region, and they play a vital role in river runoff. Therefore, it is crucial to monitor the glaciers and snow cover on a spatiotemporal basis to better understand the changes in their dynamics and their impact on river runoff. A significant amount of data is necessary to comprehend the dynamics of snow. Yet, the absence of weather stations in inaccessible locations and high elevation present multiple challenges for researchers through field surveys. However, the advancements made in remote sensing have become an effective tool for studying snow. In this article, the snow cover area (SCA) was analysed over the Beas River basin, Western Himalayas for the period 2003 to 2018. Moreover, its sensitivity towards temperature and precipitation was also analysed. To perform the analysis, two datasets, i.e., MODIS-based MOYDGL06 products for SCA estimation and the European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis of the Global Climate (ERA5) for climate data were utilized. Results showed an average SCA of ~56% of its total area, with the highest annual SCA recorded in 2014 at ~61.84%. Conversely, the lowest annual SCA occurred in 2016, reaching ~49.2%. Notably, fluctuations in SCA are highly influenced by temperature, as evidenced by the strong connection between annual and seasonal SCA and temperature. The present study findings can have significant applications in fields such as water resource management, climate studies, and disaster management.

2.
Eur J Pharm Biopharm ; 191: 150-157, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37661024

RESUMO

Breakthrough advances in protein therapeutics and sustained release systems continue to fuel innovation in novel, non-invasive polymeric platforms for delivery of biologicals. Despite the bench potential and proof-of-concept work, market analysis still shows biologicals to be predominantly injections. Characterized by insufficient secretion of growth hormone by the pituitary gland, growth hormone deficiency (GHD) is a rare disorder. Currently, chronic somatropin (r-hGH) replacement therapy is only available as subcutaneous injections administered several times a week. We aim to prepare large, porous, biodegradable and aerodynamically light microparticles as tunable carriers for pulmonary r-hGH delivery. We developed a range of microparticles using PLGA 5050 1Awith sizes between 5 µm and 13 µm, densities lower than 0.4 g/cc and aerodynamic diameters lower than 6 µm. Polyethylene glycol's multitude of advantages - plasticizing PLGA, improving the biocompatibility of the system and preventing protein burst release - have been extensively studied, making it our excipient (pore-former) of choice. Drug loading was characterized at pH 4.0 (acidic), 5.3 (pI) and pH 7.2 (neutral) and was a result of an interplay of electrostatic and hydrophobic interactions between the polymer and somatropin. Considering the physicochemical interactions, we observed some pH dependent protein unfolding characterized by reduction in intrinsic fluorescence of the Tryptophan 86 residue at 331 nm. The secondary ⍺-helix structure characterized by 2 negative minima at 209 nm and 222 nm in the circular dichroism spectra, was intact at all pH values. R-hGH was released over a period of seven days, and the release profile was a function of the microparticle porosity.

3.
Heliyon ; 9(3): e14625, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37101477

RESUMO

The six-sigma methodology has been adopted by the industry as a business management tool to improve operational capabilities and reduce defects in any process. This study aims to present a case study on the implementation of the Six-Sigma DMAIC methodology with the purpose to reduce the rejection rate of rubber weather strips manufactured by XYZ Ltd. (name changed) situated in Gurugram, India. Weather strips are used in all four doors of cars for noise reduction, waterproofing, dust proofing, soundproofing, windproofing, and for improving air conditioning cooling, and heating effects. The overall rejection rate of both front and rear door rubber weather strips was 5.5% which was causing a huge loss to the company. The average rejection rate of rubber weather strips per day reduced from 5.5% to 3.08%. After implementing the Six-Sigma project findings the rejection was reduced from 153 pieces to 68 pieces helped the industry in saving the cost of a compound by Rs. 15,249 per month. The sigma level improved from 3.9 to 4.45 within three months with the implementation of one Six-Sigma project solution. The company was highly concerned about reducing the high rejection rate of rubber weather strips and decided to deploy Six Sigma DMAIC as a quality improvement tool. The industry was keen to reduce this high rejection rate to 2% and this target was materialized with the application of the Six-Sigma DMAIC methodology. The novelty of this study is to analyze performance improvement considering the Six Sigma DMAIC methodology to reduce the rejection rate of rubber weather strip manufacturing companies.

4.
EBioMedicine ; 86: 104361, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36423375

RESUMO

BACKGROUND: Vaginal products for HIV prevention that can be used on-demand before or after sex may be a preferable option for women with low frequency or unplanned sexual activity or who prefer not to use daily or long-acting pre-exposure prophylaxis (PrEP). We performed dose ranging pharmacokinetics (PK) and efficacy studies of a vaginally applied insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) in macaques under PrEP or post-exposure prophylaxis (PEP) modalities. METHODS: PK studies were performed in 3 groups of pigtailed macaques receiving inserts with different fixed-dose combinations of TAF and EVG (10/8, 20/16 and 40/24 mg). PrEP and PEP efficacy of a selected insert was investigated in a repeat exposure vaginal SHIV transmission model. Inserts were administered 4 h before (n = 6) or after (n = 6) repeated weekly SHIV exposures. Infection outcome was compared with macaques receiving placebo inserts (n = 12). FINDINGS: Dose ranging studies showed rapid and sustained high drug concentrations in vaginal fluids and tissues across insert formulations with minimal dose proportionality. TAF/EVG (20/16 mg) inserts were selected for efficacy evaluation. Five of the 6 animals receiving these inserts 4 h before and 6/6 animals receiving inserts 4 h after SHIV exposure were protected after 13 challenges (p = 0.0088 and 0.0077 compared to placebo, respectively). The calculated PrEP and PEP efficacy was 91.0% (95% CI = 32.2%-98.8%) and 100% (95% CI = undefined), respectively. INTERPRETATION: Inserts containing TAF/EVG provided high protection against vaginal SHIV infection when administered within a 4 h window before or after SHIV exposure. Our results support the clinical development of TAF/EVG inserts for on-demand PrEP and PEP in women. FUNDING: Funded by CDC intramural funds, an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002), and by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Agency for International Development (USAID) under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Animais , Feminino , Adenina , Fármacos Anti-HIV/uso terapêutico , Fumaratos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Macaca , Tenofovir/uso terapêutico
5.
Pharm Res ; 39(5): 1001-1017, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35505262

RESUMO

PURPOSE: Use of Flory-Huggins interaction parameter and contact angle values to predict the suitability of the drug-polymer system for the production and stability of nanosuspensions. MATERIAL AND METHODS: Melting point depression of the drug was measured using differential scanning calorimetry. Interaction parameter, χ, was calculated using the melting point depression data to elucidate the drug-polymer interaction strength to predict the suitability of the drug-polymer system for the production and stability of nanosuspensions. Contact angle of the drug films were measured with purified water and 0.1%w/w polymer solutions to predict polymer's suitability for the production and stability of nanosuspension. Nanosuspensions were manufactured to validate the application of the melting point depression approach along with surface property information. RESULTS: All three polymers, HPMC, Soluplus®, and poloxamer exhibited a negative interaction parameter with naproxen and budesonide. Higher negative interaction parameter values for the naproxen-polymer system indicated stronger drug-polymer interactions, while smaller negative interaction parameter values for the budesonide-polymer system indicated weaker drug-polymer interactions. Interaction parameter was not obtained for fenofibrate with HPMC and Soluplus®, and similarly, no interaction parameter was obtained for carvedilol with HPMC, most likely due to weaker drug-polymer interactions. All three polymers provided lower equilibrium contact angle values when compared to purified water, indicating an affinity for polymers. CONCLUSIONS: Successful production and stability of several nanosuspensions were correlated with Flory-Huggins's interaction parameter and contact angle values. In the absence of melting point depression, contact angle values can also be used predict the agglomeration tendencies as we have shown for this study.


Assuntos
Naproxeno , Polímeros , Budesonida , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Polímeros/química , Solubilidade , Água
6.
AAPS PharmSciTech ; 21(8): 299, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33140227

RESUMO

Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, α-asarone, for the treatment of brain-related diseases. However, α-asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of α-asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of α-asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free α-asarone, significantly higher levels of α-asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of α-asarone in the plasma, but also transport α-asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound α-asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.


Assuntos
Anisóis/farmacocinética , Encéfalo/metabolismo , Lipídeos/química , Nanopartículas/química , Administração Intravenosa , Derivados de Alilbenzenos , Animais , Disponibilidade Biológica , Transporte Biológico , Barreira Hematoencefálica , Camundongos , Distribuição Tecidual
7.
Eur J Pharmacol ; 886: 173548, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-32926918

RESUMO

The global pandemic COVID-19, caused by novel coronavirus SARS-CoV-2, has emerged as severe public health issue crippling world health care systems. Substantial knowledge has been generated about the pathophysiology of the disease and possible treatment modalities in a relatively short span of time. As of August 19, 2020, there is no approved drug for the treatment of COVID-19. More than 600 clinical trials for potential therapeutics are underway and the results are expected soon. Based on early experience, different treatment such as anti-viral drugs (remdesivir, favipiravir, lopinavir/ritonavir), corticosteroids (methylprednisolone, dexamethasone) or convalescent plasma therapy are recommended in addition to supportive care and symptomatic therapy. There are several treatments currently being investigated to address the pathological conditions associated with COVID-19. This review provides currently available information and insight into pathophysiology of the disease, potential targets, and relevant clinical trials for COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , COVID-19 , Ensaios Clínicos como Assunto , Humanos , Pandemias
8.
Materials (Basel) ; 13(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979359

RESUMO

An increase in the generation of industrial waste materials such as pond ash and brick kiln dust represents a serious threat to the earth's environment. The waste materials have novel characteristics and therefore their physical, chemical, mineralogical, morphological, mechanical, and toxicity characteristics were determined so that these materials can be incorporated as construction materials based on technical and environmental considerations. The purpose of this study is to utilize the wastes in the stabilization of clay geomaterial to outperform existing problems of inadequate strength and stiffness of the subgrade layer in flexible pavements. Mixtures of geomaterials, containing pond ash, brick kiln dust, and their combination were prepared and important engineering characteristics such as the plasticity, compaction, and strength of the mixtures were examined. The measurement of response to dynamic loading is a pre-condition for the accurate characterization of geomaterials used in pavement construction. Using advanced cyclic triaxial testing, this study evaluates the performance of pond ash and brick kiln dust in increasing the stiffness of the geomaterial under cyclic loading. To stimulate the worst field conditions, the stiffness and strength tests were performed under standard and four-day water-soaked conditions. The implementation of several stress-dependent models for the prediction of stiffness was examined. Pond ash and brick kiln dust were found to be effective in increasing the stiffness and strength of the geomaterial. The wastes were the most effectual when added in combination to the geomaterial. The characterization of the wastes was informative in understanding the governing mechanism prevalent in the waste stabilized mixtures. The toxicity characterization study revealed the non-toxic and non-hazardous nature of the waste materials, permitting their use in the construction of pavements. This study recommends the use of wastes in the subgrade of flexible pavements. Further research is needed for performance evaluation of the wastes on silt and sand geomaterials for their wider application.

9.
Int J Pharm ; 575: 118946, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837407

RESUMO

This study aimed to determine if an ionic liquid resulted from the combination of naproxen and lidocaine and the impact that varying the molar percentage of each component had on thermal behavior. Samples were prepared by mixing naproxen and lidocaine in tetrahydrofuran (THF), followed by solvent removal using a vacuum oven. Thermal events were investigated using differential scanning calorimetry (DSC) and the extent of proton transfer was probed using Fourier-Transform Infrared Spectroscopy (FTIR). The binary samples that had a higher molar percentage of naproxen formed a 2:1 naproxen to lidocaine complex, with a melting temperature in the range of 82-85 °C. This complex was determined to be a peritectic composition of naproxen and lidocaine and spectroscopic analysis confirmed the complex had ionic liquid character as well as hydrogen bonding interactions. Binary samples that contained a greater molar percentage of lidocaine formed high-order complexes of varying stoichiometry with melting temperatures below 50 °C. Spectroscopic analysis determined that a greater molar concentration of lidocaine drove more eutectic behavior, although some ionization was also present. The conclusion from this study was that naproxen and lidocaine form an ionic liquid material at a peritectic point corresponding to 2 mol of naproxen to 1 mol of lidocaine. At molar concentrations of greater lidocaine than naproxen, higher order complexes form which are largely driven by eutectic behavior.


Assuntos
Química Farmacêutica/métodos , Líquidos Iônicos/química , Lidocaína/química , Naproxeno/química , Varredura Diferencial de Calorimetria , Furanos/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
10.
Growth Horm IGF Res ; 42-43: 86-93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30368133

RESUMO

Delivery of protein drugs would be an effective approach if mechanistic understanding of protein adsorption at solid/liquid surface is obtained and nonspecific adsorption can be controlled. This study involves evaluation of the thermodynamic parameters for interaction between recombinant human growth hormone (r-hGH) and nanoparticles of poly (lactic- co- glycolic) acid polymer of different molecular weight. Energy changes related to protein-nanoparticle interactions are usually very small and isothermal titration calorimetry (ITC) is the only technique that determines the binding constant (Ka), enthalpy, (ΔH) and stoichiometry, (n) in a single experiment. Therefore, we used ITC to study the energetics of the binding of r-hGH with PLGA nanoparticles. The largely negative ∆H and ∆S suggested that binding was driven by non-classical hydrophobic effect for interaction with PLGA 50501A and PLGA 8515E nanoparticles at pH 7.2 where higher surface coverage was noted for the latter. Endothermic, entropically driven reaction was observed upon interaction of r-hGH with PLGA 5050 5E nanoparticles at pH 7.2, PLGA 5050 1A nanoparticles at pH 5.3 and pH 4.0. Moreover, negative value of ΔCp for PLGA 50501A NPs at pH 7.2 indicated cooperative disorder of hydrogen-bonding networks and no evidence of hydrophobic elements. ITC proved to be very efficient method in studying the thermodynamics of the protein polymer interaction. In agreement with results from previous studies using fluorescence spectroscopy, circular dichroism and dynamic light scattering in our laboratory, this study demonstrated that adsorption can be controlled by selecting the polymer of low to moderate hydrophobicity depending on the pH of media.


Assuntos
Hormônio do Crescimento Humano/química , Hormônio do Crescimento Humano/metabolismo , Polímeros/química , Polímeros/metabolismo , Termodinâmica , Calorimetria , Entropia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica
11.
Pharm Res ; 35(5): 98, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29546461

RESUMO

PURPOSE: Despite the fact that r-hGH was first approved for use by FDA in 1995 and the conventional dosage form in the market has a limitation of daily subcutaneous injections, there remains a lack of sustained delivery system in the market. Nutropin depot, a long-acting dosage form of r-hGH was approved for marketing by FDA in 1999, however, it was discontinued in 2004. Since then, unabating efforts have been made to develop biodegradable polymer based formulations for r-hGH delivery. However, grey area is the comprehension of structural stability of r-hGH at an interface with the polymer and it is of utmost important to attain safe and efficacious sustained delivery system. The purpose of this study was to evaluate the changes in structure of r-hGH upon adsorption at biodegradable PLGA nanoparticles of different hydrophobicity as a function of pH. METHODS: DLS, fluorescence spectroscopy, and CD were collectively employed to evaluate structural changes in r-hGH. RESULTS: The studies revealed that r-hGH is most stable with low to high hydrophobicity PLGA grades under pH 7.2 followed by 5.3. CONCLUSION: Overall, the nature and magnitude of structural changes observed has a strong dependence on the pH and differences and degree of hydrophobicity of PLGA.


Assuntos
Composição de Medicamentos/métodos , Hormônio do Crescimento Humano/química , Nanopartículas/química , Dicroísmo Circular , Estabilidade de Medicamentos , Difusão Dinâmica da Luz , Hormônio do Crescimento Humano/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Estrutura Terciária de Proteína , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Espectrometria de Fluorescência , Propriedades de Superfície
12.
AAPS PharmSciTech ; 17(6): 1376-1382, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26753818

RESUMO

A critical issue for alcohol-induced liver disease (ALD) therapeutics is the lack of a highly efficient delivery system. In this study, a Puerarin-propylene glycol-liposome system was prepared for the purpose of targeting puerarin, an isoflavon, to the liver. Transmission electron microscope (TEM) results showed the liposomes to be spherical in shape with an average diameter of 182 nm with a polydispersity index of 0.239. The zeta potential of the particles was about -30 mV. The entrapment efficiency of puerarin was above 90%. MTT-based assay in HpeG2 cells showed no significant cytotoxicity in the presence of up to 25% concentration of the system containing 3% puerarin. In vivo performance of this system was studied in mice. Pharmacokinetics and distribution of puerarin-PG-liposome system was studied relative to puerarin solution at the same dose levels. The results show that puerarin-PG-liposome prolonged drug retention time and decreased elimination of puerarin in mice (AUC of liposome system and solution was 9.5 and 4.0 mg h L-1, respectively). Furthermore, propylene glycol (PG)-liposome system enhanced puerarin distribution into liver and spleen, while decreasing puerarin distribution in other tissues. Overall, the puerarin-PG-liposome system showed enhanced therapeutic effect in mice with ALD.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Isoflavonas/química , Isoflavonas/farmacologia , Lipossomos/química , Fígado/efeitos dos fármacos , Propilenoglicol/química , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Etanol/efeitos adversos , Células Hep G2 , Humanos , Isoflavonas/farmacocinética , Fígado/metabolismo , Camundongos , Tamanho da Partícula , Baço/metabolismo , Distribuição Tecidual
13.
Drug Discov Ther ; 8(4): 165-72, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25262595

RESUMO

We discuss the design of novel amphiphilic oligopeptides with hydrophobic and cationic amino acids to serve as models to understand peptide-DNA assembly. Biophysical and thermodynamic characterization of interaction of these amphiphilic peptides with plasmid DNA is presented. Peptides with at least +4 charges favor stable complex formation. Surface potential is dependent on the type of hydrophobic amino acid for a certain charge. Thermodynamically it is a spontaneous interaction between most of the peptides and plasmid DNA. Lys(7) and Tyr peptides with +4/+5 charges indicate cooperative binding with pDNA without saturation of interaction while Val(2)-Gly-Lys(4), Val-Gly-Lys(5), and Phe-Gly-Lys(5) lead to saturation of interaction indicating condensed pDNA within the range of N/Ps studied. We show that the biophysical properties of DNA-peptide complexes could be modulated by design and the peptides presented here could be used as building blocks for creating DNA-peptide complexes for various biomedical applications, mainly nucleic acid delivery.


Assuntos
DNA/química , Desenho de Fármacos , Oligopeptídeos/química , Plasmídeos , Termodinâmica
14.
Indian J Microbiol ; 50(4): 390-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22282605

RESUMO

Experiments were conducted both under in vitro and in situ conditions to determine the biodegradation potential of button mushroom spent substrate (SMS) and its dominating microbes (fungi and bacteria) for carbendazim and mancozeb, the commonly used agricultural fungicides. During 6 days of incubation at 30 ± 2°C under broth culture conditions, highest degradation of carbendazim (17.45%) was recorded with B-1 bacterial isolate, while highest degradation of mancozeb (18.05%) was recorded with Trichoderma sp. In fungicide pre-mixed sterilized SMS, highest degradation of carbendazim (100.00-66.50 µg g(-1)) was recorded with mixed inoculum of Trichoderma sp. and Aspergillus sp., whereas highest degradation of mancozeb (100.00-50.50 µg g(-1)) was with mixed inoculum of Trichoderma sp., Aspergillus sp. and B-I bacterial isolate in 15 days of incubation at 30 ± 2°C. All these microbes both individually as well as in different combinations grew well and produced extracellular lignolytic enzymes on SMS, which helped in fungicides degradation. Under in situ conditions, among three different proportions of SMS (10, 20 and 30%, w/w) mixed with fungicide pre-mixed soil (100 µg g(-1) of soil), the degradation of carbendazim was highest in 30% SMS treatment, while for mancozeb it was in 20% SMS treatment. The residue levels of both fungicides decreased to half of their initial concentration after 1 month of SMS mixing.

15.
Chem Biol Drug Des ; 73(5): 502-10, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19366359

RESUMO

There is a need to understand the thermodynamics of interaction of cationic peptides with DNA to design better peptide based non-viral gene delivery vectors. The main aim of this study was to understand the influence of N-terminal hydrophobicity of cationic amphiphilic peptides on thermodynamics of interaction with plasmid DNA. The model peptides used were TATPTD and TATPTDs modified at the N-terminal with hydrophobic amino acids. The thermodynamic binding data from isothermal titration calorimetry were compared with ethidium bromide analysis and ultrafiltration to correlate the binding parameters with the structural features of the various peptides used. It was observed that peptides having a smaller hydrophobic domain at the N-terminal have good DNA condensing ability compared with the ones with a longer hydrophobic domain. Calorimetry of peptides that reached saturation binding indicated that enthalpy and entropy are favorable for the interaction. Moreover, the interaction of these peptides with DNA appears to be predominantly electrostatic.


Assuntos
DNA/química , Peptídeos/química , Plasmídeos/química , Sequência de Aminoácidos , Calorimetria , Cátions , Etídio/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/síntese química , Ligação Proteica , Termodinâmica
16.
Int J Pharm ; 369(1-2): 162-9, 2009 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-19038320

RESUMO

A series of transcriptional activator (TAT)-protein transduction domains (PTDs) modified with hydrophobic amino acids were used as model cationic amphiphilic peptides to study the effect of hydrophobicity on interaction of such peptides with plasmid DNA. The peptide-DNA complexes were analyzed by dynamic light scattering and gel electrophoresis to determine their size and electrokinetic properties at various +/- charge ratios. Peptides in solution were found to have a tendency to aggregate and the hydrodynamic size of the aggregates depends on the structure of peptide. Peptides with smaller hydrophobic residues at the N-terminal formed smaller complexes with DNA compared to the ones with larger hydrophobic tails. DNA complexes having peptides with more than one hydrophobic moiety at the N-terminal had a tendency to aggregate. Among the peptides having single hydrophobic amino acid at the N-terminal, DNA complexes of Tyr-TAT and Phe-TAT were found to be stable in solution. The size of the hydrophobic domain and the type of hydrophobic amino acid at the N-terminal of cationic amphiphilic peptides play an important role not only in the complex formation but also in stabilizing the system. The studies presented here indicate that there is a potential for strategic development of these peptides into potential non-viral gene delivery vectors.


Assuntos
DNA/administração & dosagem , Produtos do Gene tat/química , Técnicas de Transferência de Genes , Peptídeos/química , Sequência de Aminoácidos , Cátions/química , Eletroforese em Gel de Ágar , Vetores Genéticos , Interações Hidrofóbicas e Hidrofílicas , Luz , Tamanho da Partícula , Plasmídeos/administração & dosagem , Espalhamento de Radiação
17.
Int J Pharm ; 351(1-2): 282-8, 2008 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-18036751

RESUMO

The objective of the present study is to formulate Naproxen nanosuspensions at high drug concentrations of up to 300 mg/ml using ball milling and is to investigate the additive effect between hydroxypropyl cellulose (HPC) and arginine hydrochloride as stabilizers. The nanosuspensions were obtained at different arginine hydrochloride/polymer weight ratios. Stability of Naproxen suspensions at 100 and 300 mg/ml was determined over a period of 14 days by measuring the particle size. The control, which contained only drug and buffers without the stabilizers agglomerated immediately after preparation. The study of the effect of arginine hydrochloride as a primary stabilizer indicated that arginine hydrochloride levels of up to 0.8% (w/v) were not able to help reduce particle size below one micron, and were also not able to provide stabilization to the suspensions on storage. Therefore, HPC was also added to the system to increase suspensions stability, presumably by a steric repulsion mechanism. When the Naproxen concentration was increased to 300 mg/ml, 1% (w/v) HPC was not able to provide good stabilization and it was found that arginine hydrochloride increased the stabilization efficiency of 1% (w/v) HPC by preventing flocculation. When HPC level was increased to 4% (w/v), HPC was high enough to sufficiently stabilize the nanosuspensions for 2 weeks and thereby could maintain the mean size diameter of the suspensions without the presence of arginine hydrochloride. Furthermore, stable nanosuspensions were successfully lyophilized without the use of additional cryoprotectants.


Assuntos
Anti-Inflamatórios não Esteroides/química , Arginina/química , Celulose/análogos & derivados , Excipientes/química , Naproxeno/química , Celulose/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Liofilização , Nanopartículas , Tamanho da Partícula , Solubilidade , Suspensões , Fatores de Tempo
18.
Indian J Microbiol ; 48(3): 389-96, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23100738

RESUMO

Out of 26 strains of Volvariella volvacea used, 18 were of 'typical' type and possessed all the characteristics of a normal V. volvacea mycelium, while the rest 4 'atypical' type strains showed completely distinct mycelial growth characteristics. The remaining 4 strains grew very slowly and exhibited growth characteristics of single spore isolates of V. volvacea. Strains varied in their extracellular lignocellulolytic activities and strains; OE-274, OE-272 and OE-210 with high ligninase enzymes (laccase and polyphenol oxidase) activities, gave highest mushroom yield on pasteurized paddy straw substrate. On the composted paddy straw substrate, additional two strains, OE-213 and OE-215 with lower activities of ligninases also gave higher mushroom yield. Mushrooms were harvested 3 to 4 d early from the composted substrate than on the pasteurized substrate. Activities of endoglucanase, laccase and polyphenol oxidase were found to be more crucial for mushroom yield on pasteurized substrate, while xylanase and ß-glucosidase were more important for composted substrate. Strains also varied in their fruiting bodies quality and the substrate used for mushroom cultivation also affected the fruiting body quality. The superior yielding strains varied in shape, size, weight, colour and contents of sodium and potassium in their fruiting bodies; while contents of carbon, calcium and protein did not vary much with the strains.

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