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1.
J Med Virol ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578548

RESUMO

Dengue fever is a self-limiting, acute febrile illness caused by an arbovirus. This infection may be asymptomatic or symptomatic with its potential life-threatening form as DHF/DSS. Severe dengue cases occur typically in children due to overproduction of pro-inflammatory and anti-inflammatory cytokines (called cytokines storm) as well as increased microvascular permeability in them. This study aimed to find prevalent circulating dengue serotype and their clinicopathological association among pediatric patients admitted to tertiary care hospitals in Kolkata, India. Overall, 210 patients were approached and among them, 170 dengue suspected children admitted to three tertiary care hospitals were included in this study. Dengue samples were screened for the presence of NS1 antigen and dengue IgM antibodies by ELISA. Viral RNA was extracted from NS1 seropositive serum samples and subjected to molecular serotyping by semi-nested RT-PCR. All patients were followed up for clinical manifestations and biochemical parameters associated with dengue. Co-circulation of all four serotypes was observed and DENV2 was the major circulating strain. Physiological classification of associated clinical symptoms was done and represented as a percentage variable. A multivariate logistic regression approach was used for making a regression model including dengue-associated clinical symptoms with dengue positivity and negativity as dependent variables. Thrombocytopenia was observed in 69% of patients and the commonest bleeding manifestation was petechia. Liver function profiles of infected patients were observed during follow-up and represented using a box plot. A significant change in trends of dengue-associated clinical manifestations and differential expression of liver functional profile with different phase transitions of dengue fever was obtained in the study population. This article is protected by copyright. All rights reserved.

2.
Front Chem ; 10: 855132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372271

RESUMO

The computational modeling supported with experimental results can explain the overall structural packing by predicting the hydrogen bond interactions present in any cocrystals (active pharmaceutical ingredients + coformer) as well as salts. In this context, the hydrogen bonding synthons, physiochemical properties (chemical reactivity and stability), and drug-likeliness behavior of proposed nicotinamide-oxalic acid (NIC-OXA) salt have been reported by using vibrational spectroscopic signatures (IR and Raman spectra) and quantum chemical calculations. The NIC-OXA salt was prepared by reactive crystallization method. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) techniques were used for the characterization and validation of NIC-OXA salt. The spectroscopic signatures revealed that (N7-H8)/(N23-H24) of the pyridine ring of NIC, (C═O), and (C-O) groups of OXA were forming the intermolecular hydrogen bonding (N-H⋯O-C), (C-H⋯O═C), and (N-H⋯O═C), respectively, in NIC-OXA salt. Additionally, the quantum theory of atoms in molecules (QTAIM) showed that (C10-H22⋯O1) and (C26-H38⋯O4) are two unconventional hydrogen bonds present in NIC-OXA salt. Also, the natural bond orbital analysis was performed to find the charge transfer interactions and revealed the strongest hydrogen bonds (N7-H8⋯O5)/(N23-H24⋯O2) in NIC-OXA salt. The frontier molecular orbital (FMO) analysis suggested more reactivity and less stability of NIC-OXA salt in comparison to NIC-CA cocrystal and NIC. The global and local reactivity descriptors calculated and predicted that NIC-OXA salt is softer than NIC-CA cocrystal and NIC. From MESP of NIC-OXA salt, it is clear that electrophilic (N7-H8)/(N23-H24), (C6═O4)/(C3═O1) and nucleophilic (C10-H22)/(C26-H38), (C6-O5)/(C3-O2) reactive groups in NIC and OXA, respectively, neutralize after the formation of NIC-OXA salt, confirming the presence of hydrogen bonding interactions (N7-H8⋯O5-C6) and (N23-H24⋯O2-C3). Lipinski's rule was applied to check the activeness of salt as an orally active form. The results shed light on several features of NIC-OXA salt that can further lead to the improvement in the physicochemical properties of NIC.

3.
Front Chem ; 9: 708538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381761

RESUMO

The pharmaceutical cocrystal of caffeine-citric acid (CAF-CA, Form II) has been studied to explore the presence of hydrogen bonding interactions and structure-reactivity-property relationship between the two constituents CAF and Citric acid. The cocrystal was prepared by slurry crystallization. Powder X-ray diffraction (PXRD) analysis was done to characterize CAF-CA cocrystal. Also, differential scanning calorimetry (DSC) confirmed the existence of CAF-CA cocrystal. The vibrational spectroscopic (FT-IR and FT-Raman) signatures and quantum chemical approach have been used as a strategy to get insights into structural and spectral features of CAF-CA cocrystal. There was a good correlation among the experimental and theoretical results of dimer of cocrystal, as this model is capable of covering all nearest possible interactions present in the crystal structure of cocrystal. The spectroscopic results confirmed that (O33-H34) mode forms an intramolecular (C25 = O28∙∙∙H34-O33), while (O26-H27) (O39-H40) and (O43-H44) groups form intermolecular hydrogen bonding (O26-H27∙∙∙N24-C22, O39-H40∙∙∙O52 = C51 and O43-H44∙∙∙O86 = C83) in cocrystal due to red shifting and increment in bond length. The quantum theory of atoms in molecules (QTAIM) analysis revealed (O88-H89∙∙∙O41) as strongest intermolecular hydrogen bonding interaction with interaction energy -12.4247 kcal mol-1 in CAF-CA cocrystal. The natural bond orbital analysis of the second-order theory of the Fock matrix highlighted the presence of strong interactions (N∙∙∙H and O∙∙∙H) in cocrystal. The HOMO-LUMO energy gap value shows that the CAF-CA cocrystal is more reactive, less stable and softer than CAF active pharmaceutical ingredients. The electrophilic and nucleophilic reactivities of atomic sites involved in intermolecular hydrogen bond interactions in cocrystal have been demonstrated by mapping electron density isosurfaces over electrostatic potential i.e. plotting molecular electrostatic potential (MESP) map. The molar refractivity value of cocrystal lies within the set range by Lipinski and hence it may be used as orally active form. The results show that the physicochemical properties of CAF-CA cocrystal are enhanced in comparison to CAF (API).

4.
Artigo em Inglês | MEDLINE | ID: mdl-35010473

RESUMO

AIM: To assess the knowledge and perceptions of COVID-19 among pediatric dentists based on their dependent source of information. METHODS: A descriptive-analytical cross-sectional survey using a self-administered questionnaire with 23 questions was sent via Google forms to pediatric dentists. All participants were divided into three groups [postgraduate residents (PGs), private practitioners (PP), and faculty (F)]. The comparison of knowledge and perception scores was made based on occupation, source of information, and descriptive statistics used for the analysis using SPSS 21.0 (IBM, Armonk, NY, USA). RESULTS: A total of 291 pediatric dentists completed the survey, and the majority of them were females (65%). Overall, good mean scores were obtained for knowledge (9.2 ± 1.07) and perceptions (5.6 ± 1.5). The majority of the participants used health authorities (45%) to obtain updates on COVID-19, while social media (35.1%) and both (19.6%) accounted for the next two. A statistically significant difference (p < 0.05) was found among different pediatric dentists groups for relying on the source of information. CONCLUSION: Overall good pediatric dentists showed sufficient knowledge regarding COVID-19. The pediatric dentists' age, occupation, and source of information influenced knowledge regarding COVID-19, whereas perceptions were influenced by age and gender of the participants. Health authorities successfully educated pediatric dentists than the social media.


Assuntos
COVID-19 , Criança , Controle de Doenças Transmissíveis , Estudos Transversais , Odontólogos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Padrões de Prática Odontológica , SARS-CoV-2 , Inquéritos e Questionários
5.
Curr Drug Deliv ; 17(10): 845-860, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294036

RESUMO

Quercetin (QT, 3,3',4',5,7-pentahydroxyflavone), is a natural flavonoid with nutritional value and acts as a potential free-radical scavenger (antioxidant). QT has also been explored for its anti-cancer as well as anti-proliferative activities against numerous cancerous cells. Moreover, QT exhibits significant pro-apoptotic activity against tumor cells and is well established to control the growth of different carcinoma cells at various phases of the cell cycle. Hence, it can reduce the burden of human solid cancer and metastasis. Both these activities have been established in a diverse class of human cell lines in-vitro as well as in animal models (in-vivo). Apart from the promising therapeutic activities of QT molecule, their applications have been limited due to some major concerns, including low oral bioavailability and poor aqueous solubility. Also, rapid gastrointestinal digestion of QT seems to be a key barrier for its clinical translations for oral drug delivery in conventional dosage form. Henceforth, to overcome these drawbacks, QT is loaded with liposomal systems, which exhibit promising outcomes in the upregulation of QT by the epithelial system and also improved its targeting at the site of action. Furthermore, Liposomes based Drug Delivery Systems (LDDS) have showed significant therapeutic activity with conjugated drug moiety and exhibit safety, biocompatibility, biodegradability, and mitigated toxicity despite having certain limitations associated with physiological and biological barriers. Herein, in this review, we have focused on the mechanism related with the chemotherapeutic activity of QT and also discussed the promising activity of QT-loaded LDDS as a potent chemotherapeutic agent for cancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Lipossomos , Neoplasias , Quercetina , Animais , Disponibilidade Biológica , Humanos , Neoplasias/tratamento farmacológico , Quercetina/administração & dosagem
6.
Drug Dev Ind Pharm ; 46(2): 188-191, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31933389

RESUMO

The crystals of paracetamol obtained by exposure of its saturation solution to DC electric field of varying duration (1-6 min) supplied by means of silver electrodes (the term coined as ENS-crystals). These ENS-crystals were analyzed for electrical properties such as dielectric constant, zeta potential, electrochemical properties such as oxidation and reduction potential (EP), current (iP), and charges (Ah) means of cyclic voltammetry. The dielectric constant is increased at 1 kHz and 100 kHz frequencies. Zeta potential is also enhanced by significant degree. Cyclic voltametric analysis reveals that the oxidizing potential and charge of paracetamol ENS-crystal is enhances by two fold. Quantitatively these changes are dependent on the duration of exposure to electrical field from 1 to 6 min. These changes in electrical and electrochemical properties of paracetamol ENS-crystals could be useful from the pharmaceutical point of view.


Assuntos
Acetaminofen/química , Cristalização , Eletrodos , Oxirredução
7.
Int J Clin Pediatr Dent ; 12(4): 288-292, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31866712

RESUMO

Statement of problem: Interactions are suspected between resin coating and elastomeric impression material. Purpose: The purpose of this study was to identify possible interactions between two impression materials and resin-coated tooth surfaces. Materials and methods: Extracted molars (n = 10) underwent 1 of the 4 procedures: control group (unsealed tooth surface/impression); IDS group (immediate dentin sealing/impression); IDS/AB group (immediate dentin sealing/air blocking/impression); IDS/AB-P group (immediate dentin sealing/air blocking/pumicing/impression). Dentin bonding agents used were Adper single bond 2 and Clearfil SE bond. Impression materials used were Impregum Soft (polyether) and Aquasil (A silicone). A stereomicroscope was used to detect any residual impression material on the bonded tooth surface. Results: The IDS group showed 100% faulty impressions. Air blocking the resin coating did not completely eliminate the oxygen-inhibited layer of Adper single bond 2. Clearfil SE Bond along with Aquasil generated ideal impressions in group IDS/AB, while all other combinations resulted in faulty impressions. The IDS/AB-P group yielded ideal impressions with Aquasil but generated faulty impressions with Impregum soft in most specimens. Conclusion: Immediate dentin sealing should be followed by air blocking and pumicing to generate ideal impressions with Aquasil (A silicone). Impregum Soft (polyether) is not recommended in combination with immediate dentin sealing. How to cite this article: Khakiani MI, Kumar V, et al. Effect of Immediate Dentin Sealing on Polymerization of Elastomeric Materials: An Ex Vivo Randomized Controlled Trial. Int J Clin Pediatr Dent 2019;12(4):288-292.

8.
Int J Clin Pediatr Dent ; 11(1): 1-6, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805226

RESUMO

Dental caries is the most common oral health disease affecting all age groups, races, and geographic locations. The need for the study was to determine the anatomical marker that could predict the taste perception and caries at an early stage. Aim of the study was to determine the correlation between digit ratio and caries experience in school-going children of south Canara region. An observational and cross-sectional pattern was adopted for the present study. The study was then evaluated to find out the correlation between the digit ratio that is thought to be predetermined with caries experience in children of age group 6 to 16 years. In the total sample of 2,037 children, the total population was divided into two categories, i.e., high digit ratio and low digit ratio. Of the total population, 1,112 had low digit ratio and 925 had high digit ratio. Caries experience was highest in low-risk group, followed by moderate, high risk, low risk, and very high risk groups. In all the categories, low digit ratio was affected more than high digit ratio. The study clearly states a positive correlation between digit ratio, taste, social behavior, and dental caries. How to cite this article: Verma P, Hegde AM. Digit Ratio and Dental Caries: A Sexually Dimorphic Trait. Int J Clin Pediatr Dent 2018;11(1):1-6.

9.
Immunology ; 154(3): 490-499, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29359328

RESUMO

Interleukin-1ß (IL-1ß) is a potent mediator of innate immunity commonly up-regulated in a broad spectrum of inflammatory diseases. When bound to its cell surface receptor, IL-1ß initiates a signalling cascade that cooperatively induces the expression of canonical IL-1 target genes such as IL-8 and IL-6. Here, we present galectin-3 as a novel regulator of IL-1ß responses in corneal keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we show that recombinant exogenous galectin-3 binds to the plasma membrane of keratinocytes and is internalized into cytoplasmic compartments. We find that exogenous galectin-3, but not a dominant negative inhibitor of galectin-3 polymerization lacking the N-terminal domain, exacerbates the response to IL-1ß by stimulating the secretion of inflammatory cytokines. The activity of galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting the conserved galactoside-binding site of galectins and did not involve interaction with IL-1 receptor 1 or the induction of endogenous IL-1ß. Consistent with these observations, we demonstrate that small interfering RNA-mediated suppression of endogenous galectin-3 expression is sufficient to impair the IL-1ß-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated protein kinase-independent manner. Collectively, our findings provide a novel role for galectin-3 as an amplifier of IL-1ß responses during epithelial inflammation through an as yet unidentified mechanism.


Assuntos
Galectina 3/metabolismo , Interleucina-1beta/metabolismo , Queratinócitos/metabolismo , Ceratite/etiologia , Ceratite/metabolismo , Células Cultivadas , Endocitose , Galectina 3/farmacologia , Humanos , Interleucina-1beta/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , Ceratite/patologia , Ligação Proteica
10.
Chemistry ; 24(8): 1905-1912, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29094420

RESUMO

Host cell surface carbohydrate receptors of bacterial adhesins are attractive targets in anti-adhesion therapy. The affinity of carbohydrate ligands with adhesins is usually found in the low µm range, which poses a problem for the design of effective inhibitors useful in therapy. In an attempt to increase the inhibitory power of carbohydrate ligands, we have combined the approach of chemical modification of ligands with their presentation as multivalent dendrimers in the design of an inhibitor of streptococcal adhesin SadP binding to its galactosyl-α1-4-galactose (galabiose) receptor. By using a phenylurea-modified galabiose-containing trisaccharide in a tetravalent dendrimeric scaffold, inhibition of adhesin at a low picomolar level was achieved. This study has resulted in one of the most potent inhibitors observed for bacterial adhesins and demonstrates a promising approach to develop anti-adhesives with the potential of practical applicability.


Assuntos
Adesinas Bacterianas/metabolismo , Dendrímeros/química , Streptococcus suis/metabolismo , Adesinas Bacterianas/química , Dendrímeros/síntese química , Dendrímeros/metabolismo , Dissacarídeos/antagonistas & inibidores , Dissacarídeos/metabolismo , Oligossacarídeos/síntese química , Oligossacarídeos/química , Oligossacarídeos/genética , Compostos de Fenilureia/química , Ligação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação
11.
J Med Chem ; 61(3): 1164-1175, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29284090

RESUMO

Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional affinities (Kd down to 1-2 nM) in symmetrically substituted thiodigalactosides as well as unsurpassed combination of high affinity (Kd 7.5 nM) and selectivity (46-fold) over galectin-1 for asymmetrical thiodigalactosides by carrying one trifluorphenyltriazole and one coumaryl moiety. Studies of the inhibitor-galectin complexes with isothermal titration calorimetry and X-ray crystallography revealed the importance of fluoro-amide interaction for affinity and for selectivity. Finally, the high affinity of the discovered inhibitors required two competitive titration assay tools to be developed: a new high affinity fluorescent probe for competitive fluorescent polarization and a competitive ligand optimal for analyzing high affinity galectin-3 inhibitors with competitive isothermal titration calorimetry.


Assuntos
Galectina 3/metabolismo , Tiogalactosídeos/química , Tiogalactosídeos/metabolismo , Proteínas Sanguíneas , Descoberta de Drogas , Galectina 3/química , Galectinas , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Especificidade por Substrato , Termodinâmica , Tiogalactosídeos/síntese química
12.
Recent Pat Drug Deliv Formul ; 11(3): 211-220, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29189186

RESUMO

BACKGROUND: Recent patents reveal that Soluplus® has proved to be a promising excipient that modulates dissolution characteristics of many active pharmaceutical ingredients (WO2016161995A1, WO2016169534A1 and WO2016165676A1). OBJECTIVE: Current article investigates stable solid solution of furosemide with Soluplus® to enhance the dissolution properties of the drug. METHOD: Drug to carrier ratios to prepare solid dispersion were selected based on the phase solubility study. Solid dispersions of furosemide with Soluplus® were prepared by solvent evaporation and fusion methods. Physicochemical parameters were characterized using Fourier transform infra-red spectrophotometer, thermo- gravimetric analyzer, differential thermal analyzer, and scanning electron microscopy. Drug release from the formulations was compared using USP type II (paddle type) dissolution apparatus containing 900 mL of phosphate buffer (pH - 6.8) maintained at 37±0.5°C at a paddle rotation speed of 50rpm. RESULTS: Fourier transform infra-red spectroscopy confirmed absence of any chemical interaction while thermo-gravimetry and differential thermal analysis showed evidences of formation of a solid solution of furosemide. No furosemide crystals were observed under scanning electron microscope in case of solid dispersion. Dissolution data indicated that furosemide dissolution was enhanced to a great extent and drug to carrier ratio of 1:10 was found to be most suitable. CONCLUSION: Solid dispersions prepared by fusion method exhibited faster drug release compared to those prepared by solvent evaporation.


Assuntos
Diuréticos/administração & dosagem , Furosemida/administração & dosagem , Diuréticos/farmacocinética , Portadores de Fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes , Furosemida/farmacocinética , Patentes como Assunto , Polietilenoglicóis , Polivinil , Solubilidade
13.
AAPS PharmSciTech ; 18(8): 2871-2888, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28424979

RESUMO

The present study aimed for in vitro-in vivo-in silico simulation studies of experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F 127 nanocapsules to ferry felodipine using GastroPlus™. The in silico parameter sensitivity analysis for pharmacokinetic parameters was initially assessed to justify the preparation of felodipine-loaded nanocapsules (FLNs) with enhanced solubility to overcome the bioavailability issues of felodipine. The overall integrated desirability ranged between 0.8187 and 0.9488 for three optimized FLNs when analyzed for mean particle size, zeta potential, encapsulation efficiency, and in vitro dissolution parameters. The morphological evaluation (SEM, TEM, and AFM) demonstrated spherical nanoparticles (200-300 nm). Validated LC-MS/MS analysis demonstrated enhanced relative bioavailability (13.37-fold) of optimized FLN as compared to suspension. The simulated regional absorption of the FLN presented significant absorption from the cecum (26.3%) and ascending colon (20.1%) with overall absorption of 67.4% from the GIT tract. Furthermore, in vitro-in vivo correlation demonstrated the Wagner-Nelson method as the preferred model as compared to mechanistic and numerical deconvolution on the basis of least mean absolute prediction error, least standard error of prediction, least mean absolute error, and maximum correlation coefficient (r 2 = 0.920). The study demonstrated enhanced oral absorption of felodipine-loaded nanocapsules, and GastroPlus™ was found to be an efficient simulation tool for in vitro-in vivo-in silico simulations.


Assuntos
Felodipino/sangue , Felodipino/química , Nanocápsulas/química , Administração Oral , Animais , Antiarrítmicos/sangue , Antiarrítmicos/química , Disponibilidade Biológica , Avaliação Pré-Clínica de Medicamentos/métodos , Tamanho da Partícula , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
14.
Int J Biol Macromol ; 102: 642-650, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28435058

RESUMO

The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 32 full factorial design was adopted for optimization of tripolyphosphate (X1) and curing time (X2). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X1 and X2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. Tmax and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability.


Assuntos
Carbazóis/química , Carbazóis/metabolismo , Quitosana/química , Portadores de Fármacos/química , Mucosa Gástrica/metabolismo , Microesferas , Propanolaminas/química , Propanolaminas/metabolismo , Disponibilidade Biológica , Carbazóis/farmacocinética , Carvedilol , Propanolaminas/farmacocinética
15.
Ther Deliv ; 8(3): 125-136, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28145826

RESUMO

The present work focuses on preparing a solidified self nano-emulsifying drug-delivery system (S-SNEDDS) to improve the in vitro dissolution of rosuvastatin and to evaluate its antihyperlipidemic activity. Powder flow characterization demonstrated good flow properties. The drug-excipient compatibility study indicates no possible interaction. Transmission electron microscopy and scanning electron microscopy revealed nonaggregated, spherical nanosized globules. The globule-size analysis revealed droplet size in nanorange (∼100 nm). S-SNEDDS exhibited improved drug release (∼95%) as compared with rosuvastatin powder (51.89%) at 60 min. Upon antihyperlipidemic study, S-SNEDDS after 14th day of treatment revealed significant reduction in cholesterol (33.47%), triglycerides (40.77%) and atherogenic index (81.28%), while high-density lipoprotein (118.43%) was increased. The study indicates the great potential of S-SNEDDS for improving oral absorption of such poorly soluble drugs and their pharmacodynamic efficacy.


Assuntos
Sistemas de Liberação de Medicamentos , Hiperlipidemias/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Animais , Disponibilidade Biológica , Dieta/efeitos adversos , Liberação Controlada de Fármacos , Emulsões , Hiperlipidemias/induzido quimicamente , Nanopartículas , Tamanho da Partícula , Pós , Ratos , Solubilidade
16.
Pharm Dev Technol ; 22(7): 910-927, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27484389

RESUMO

The study aimed to optimize self-nanoemulsifying drug delivery system using experimental design using excipients holding innate anti-mycobacterium activities followed with characterizations for responses such as optical clarity (Y1), zone of inhibition (ZOI) against Mycobacterium smegmatis strains (Y2, Y3), and globular size (Y4). The optimized formulations (OF1-OF3) were further characterized for responses and evaluated for zeta potential, minimum inhibition concentration (MIC) against non-pathogenic and tubercular strains, morphological (electron microscopy and atomic force microscopy), and confocal laser scanning microscopy (CLSM) studies. The desirability analysis suggested that the predicted values of the OF1 for the responses Y1, Y2, Y3, and Y4 were 0.137, 22.77 mm, 21.9 mm, and 191.11 nm, respectively. The morphological assessment confirmed the in vitro studies and established the inhibition mechanism as evidenced with oozing, ablation, and cell-wall fragmentation followed with cell disruption. The OF1, OF2, and OF3 showed an MIC value at 8.8 ± 0.56 mg/ml, 12.5 ± 0.22 mg/ml, and 15.0 ± 0.4 mg/ml, respectively, corroborating effectiveness against tubercular strain. CLSM studies revealed 75.1, 80.3, and 88.7% as an intense fluorescence intensity of OF1, OF2, and OF3, respectively, as compared with dye solution (∼53%). Conclusively, it can be inferred that the delivery of anti-tubercular drugs might be reassessed using excipients with inherent anti-mycobacterium activities.


Assuntos
Anti-Infecciosos , Sistemas de Liberação de Medicamentos , Lipídeos , Nanopartículas , Mycobacterium , Projetos de Pesquisa
17.
Drug Dev Ind Pharm ; 42(2): 288-306, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26087658

RESUMO

In this investigation, multivariate design approach was employed to develop self-nanoemulsifying drug delivery system (SNEDDS) of loratadine and to exploit its potential for intestinal permeability. Drug solubility was determined in various vehicles and existence of self-nanoemulsifying region was evaluated by phase diagram studies. The influence of formulation variables X1 (Capmul MCM C8) and X2 (Solutol HS15) on SNEDDS was assessed for mean globule sizes in different media (Y1-Y3), emulsification time (Y4) and drug-release parameters (Y5-Y6), to improve quality attributes of SNEDDS. Significant models were generated, statistically analyzed by analysis of variance and validated using the residual and leverage plots. The interaction, contour and response plots explicitly demonstrated the influence of one factor on the other and displayed trend of factor-effect on responses. The pH-independent optimized formulation was obtained with appreciable global desirability (0.9266). The strenuous act of determining emulsification time is innovatively replaced by the use of oil-soluble dye to produce visibly distinct globules that otherwise may be deceiving. TEM images displayed non-aggregated state of spherical globules (size < 25 nm) and also revealed the structural transitions occurring during emulsification. Optimized formulation exhibited non-Newtonian flow justified by the model-fit and also presented the stability to dilution effects and thermodynamic stress testing. The ex vivo permeation study using confocal laser scanning microscopy indicate strong potential of rhodamine 123-loaded loratadine-SNEDDS to inhibit P-gp efflux and facilitate intestinal permeation. To conclude, the effectiveness of design yields a stable optimized SNEDDS with enhanced permeation potential, which is expected to improve oral bioavailability of loratadine.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Loratadina/administração & dosagem , Animais , Antialérgicos/administração & dosagem , Antialérgicos/farmacocinética , Disponibilidade Biológica , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões , Concentração de Íons de Hidrogênio , Absorção Intestinal , Loratadina/farmacocinética , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Solubilidade , Termodinâmica
18.
Anesth Essays Res ; 9(3): 440-2, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26712994

RESUMO

D-transposition of great arteries (D-TGA) is the most common cyanotic congenital heart disease diagnosed at birth. There is ventriculoarterial discordance leading to parallel circulation. The postnatal survival depends on intercirculatory mixing of oxygenated and deoxygenated blood at various levels through atrial septal defect, ventricular septal defect or patent ductus arteriosus. The anesthesiologist must have an understanding of concepts of shunting and other long-term consequences of transposition of great arteries (TGA) in order to tailor the anesthetic technique to optimize the hemodynamic variables and oxygenation in the perioperative period. The preoperative evaluation includes echocardiography to delineate the type of TGA, associated lesions and extent and direction of shunts. Oxygen saturation is influenced by the ratio of pulmonary vascular resistance (PVR) to systemic vascular resistance. Thus, care should be taken to avoid an increase in PVR which can lead to decreased pulmonary blood flow leading to hypoxia. We report a case of an 8-year-old child with unrepaired D-TGA, who presented to us for craniotomy for drainage of brain abscess.

19.
Acta Pol Pharm ; 72(5): 999-1013, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26665408

RESUMO

The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with PEG 6000. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were characterized by X-ray diffraction, differential scanning calorimetry, FT-IR spectroscopy, Near Infrared, Raman analysis and wettability studies. The phase solubility studies and its thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions than pure drug and a linear increase in drug release was observed with an increase in carrier content. XRD, DSC, FT-IR, NIR and Raman analysis revealed the crystallinity reduction of olanzapine and its compatibility with the carrier. Wettability studies proved the increased wettability in samples due to water absorbing nature of the carrier. The possible mechanisms for increased release rate are attributed to solubilization effect of the carrier, formation of solid solution, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity, increased wettability and dispersability of drug in dissolution medium. The suggested reasons for such release behavior were found to be well supported by results of the evaluation techniques.


Assuntos
Benzodiazepinas/química , Benzodiazepinas/administração & dosagem , Varredura Diferencial de Calorimetria , Modelos Teóricos , Olanzapina , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
20.
Artigo em Inglês | MEDLINE | ID: mdl-26413122

RESUMO

CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively. The findings showed upregulated expression of NR1 and decreased binding of REST/NRSF to NR1 promoter after postnatal exposure of PBDE-209. Interestingly, supplementation with CDRI-08 significantly restored the expression of NR1 and binding of REST/NRSF to NR1 promoter near to the control value at the dose of 120 mg/kg. In conclusion, the results suggest that CDRI-08 possibly acts on glutamatergic system through expression and regulation of NR1 and may restore memory, impaired by PBDE-209 as reported in our previous study.

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