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1.
Purpose
To evaluate the use of Labrafil® M2125CS as a lipid vehicle for danazol. Further, the possibility of predicting the in vivo behavior with a dynamic in vitro lipolysis model was evaluated.Methods
Danazol (28 mg/kg) was administered orally to rats in four formulations: an aqueous suspension, two suspensions in Labrafil® M2125CS (1 and 2 ml/kg) and a solution in Labrafil® M2125CS (4 ml/kg).Results
The obtained absolute bioavailabilities of danazol were 1.5?±?0.8%; 7.1?±?0.6%; 13.6?±?1.4% and 13.3?±?3.4% for the aqueous suspension, 1, 2 and 4 ml Labrafil® M2125CS per kg respectively. Thus administration of danazol with Labrafil® M2125CS resulted in up to a ninefold increase in the bioavailability, and the bioavailability was dependent on the Labrafil® M2125CS dose. In vitro lipolysis of the formulations was able to predict the rank order of the bioavailability from the formulations, but not the absorption profile of the in vivo study.Conclusions
The bioavailability of danazol increased when Labrafil® M2125CS was used as a vehicle, both when danazol was suspended and solubilized in the vehicle. The dynamic in vitro lipolysis model could be used to rank the bioavailabilities of the in vivo data.2.
Manju Kanamala Brian D. Palmer Hamidreza Ghandehari William R. Wilson Zimei Wu 《Pharmaceutical research》2018,35(8):154
Purpose
To fabricate an acid-cleavable PEG polymer for the development of PEG-cleavable pH-sensitive liposomes (CL-pPSL), and to investigate their ability for endosomal escape and long circulation.Methods
PEG-benzaldehyde-hydrazone-cholesteryl hemisuccinate (PEGB-Hz-CHEMS) containing hydrazone and ester bonds was synthesised and used to fabricate a dual pH-sensitive CL-pPSL. Non-cleavable PEGylated pH-sensitive liposome (pPSL) was used as a reference and gemcitabine as a model drug. The cell uptake and endosomal escape were investigated in pancreatic cancer Mia PaCa-2 cells and pharmacokinetics were studied in rats.Results
The CL-pPSL showed accelerated drug release at endosomal pH 5.0 compared to pPSL. Compared to pPSL, CL-pPSL released their fluorescent payload to cytosol more efficiently and showed a 1.4-fold increase in intracellular gemcitabine concentration and higher cytotoxicity. In rats, injection of gemcitabine loaded CL-pPSL resulted in a slightly smaller Vd (149?±?27 ml/kg; 170?±?30 ml/kg) and shorter terminal T1/2 (5.4?±?0.3 h; 5.8?±?0.6 h) (both p?>?0.05) but a significantly lower AUC (p?<?0.01), than pPSL, due to the lower PEGylation degree (1.7 mol%) which means a ‘mushroom’ configuration of PEG. A five-time increase in the dose with CL-pPSL resulted in a 11-fold increase in AUC and a longer T1/2 (8.2?±?0.5 h).Conclusion
The PEG-detachment from the CL-pPSL enhanced endosome escape efficiency compared with pPSL, without significantly compromising their stealth abilities.3.
Masako Ohno Akiko Yamamoto Ayumu Ono Genta Miura Masanobu Funamoto Yasuhiko Takemoto Kinya Otsu Yasushi Kouno Tomoko Tanabe Yuiko Masunaga Shinpei Nonen Yasushi Fujio Junichi Azuma 《European journal of clinical pharmacology》2009,65(11):1097
Objective
The aim of this study was to investigate the influence of clinical and genetic factors on warfarin dose requirements in the Japanese population.Methods
We enrolled 125 patients on stable warfarin anticoagulant therapy with an international normalized ratio maintained between 1.5 and 3.0. PCR-based methods were performed to analyze genetic polymorphisms in the genes pharmacokinetically and pharmacodynamically related to warfarin reactions, including cytochrome P450 (CYP) 2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1), gamma-glutamyl carboxylase (GGCX) and factor VII (FVII).Results
The presence of CYP2C9*3 and VKORC1-1639G>A had a significant impact on the mean maintenance dose of warfarin (CYP2C9*1/*1 2.74?±?1.24 mg/day vs. *1/*3 and *3/*3 1.56?±?0.85 mg/day, P?=?0.009; VKORC1-1639AA 2.42?±?0.95 mg/day vs. GA 3.71?±?1.43 mg/day vs. GG 7.25?±?0.35 mg/day, P?<?0.001). In the multiple linear regression model, the combination of age, body surface area, and genotypes of CYP2C9*3 and VKORC1-1639G>A explained 54.8% of the variance in warfarin dose requirements.Conclusions
The influences of CYP2C9*3 and VKORC1-1639G>A on the maintenance dose of warfarin were well-defined in Japanese patients, while polymorphisms of GGCX and FVII did not affect it. The model established in this study might provide us most likely individual maintenance dose based on clinical and genetic backgrounds.4.
E. E. Perez-Guerrero L. Gonzalez-Lopez J. F. Muñoz-Valle J. C. Vasquez-Jimenez M. Ramirez-Villafaña E. N. Sanchez-Rodriguez S. R. Gutierrez-Ureña S. Cerpa-Cruz E. A. Aguilar-Chavez E. G. Cardona-Muñoz M. L. Vazquez-Villegas A. M. Saldaña-Cruz N. A. Rodriguez-Jimenez N. S. Fajardo-Robledo J. I. Gamez-Nava 《Inflammopharmacology》2018,26(6):1375-1381
Objectives
To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs).Methods
A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥?6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 <?3.2; and (2) patients without a response to DMARDs, with persistent DAS28?≥?3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression.Results
Serum P-gp levels were significantly higher in RA patients (n?=?151) than in the controls (n?=?30) (158.70?±?182.71 ng/mL vs. 14.12?±?8.97 ng/mL, p?<?0.001). The P-gp level was correlated with the DAS28 score (r?=?0.39, p?<?0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206?±?21.47 ng/mL vs 120.60?±?15.70 ng/mL; p?=?0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54–7.27, p?=?0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29–5.40, p?=?0.01).Conclusion
Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.5.
Purpose
In the present investigation, we prepared and evaluated the paclitaxel loaded riboflavin and thiamine conjugated multi walled carbon nanotubes (PTX-Rf-MWCNTs and PTX-Tm-MWCNTs) for targeted delivery to cancer employing MCF-7 cancer cell lines.Methods
The developed conjugates were characterized using FTIR, NMR spectroscopy, electron microscopy drug loading, release, stability, hemolytic, ex vivo and in vivo studies etc.Results
The percent entrapment efficiency was found to be 87.92?±?0.48 and 82.75?±?0.47% of PTX-Tm-MWCNTs, PTX-Rf-MWCNTs, respectively. The percent hemolysis of purified MWCNTs, PTX-MWCNTs, PTX-Tm-MWCNTs and PTX-Rf-MWCNTs was found to be 20.49?±?0.97, 37.39?±?0.78, 14.61?±?0.84 and 11.17?±?0.77% respectively. The PTX-Tm-MWCNTs and PTX-Rf-MWCNTs showed more cytotoxic effect as compared to PTX and PTX-MWCNTs with PTX-Rf-MWCNTs exhibiting the maximum cytotoxic potential.Conclusion
Thus in final outcome, we concluded that the riboflavin and thiamine conjugated MWCNTs shown great promising potential in the treatment of cancer, but more exhaustive data is needed in future.6.
Purpose
Current in vitro disintegration methods for polymeric films are qualitative and introduce significant user bias. The goal of these studies is to develop a novel, quantitative disintegration technique which can be used to characterize polymeric films in vitro.Methods
A method was developed using a Texture Analyzer instrument to evaluate film disintegration. Solvent-casted, clinically advanced, anti-HIV, vaginal films as well as marketed vaginal films were used throughout these studies. Method development followed a quality by design (QbD) process and was used to evaluate film products.Results
The current method developed provided reproducible, quantitative disintegration times for the commercially available vaginal contraceptive film (57.88?±?5.98 s). It distinguished between two clinically advanced antiretroviral containing films based on disintegration time (p value <?0.001): the tenofovir film (41.28?±?3.35 s) and the dapivirine film (88.36?±?10.61 s). This method could also distinguish between tenofovir and dapivirine films which had been altered in terms of volume (p?<?0.0001) and formulation (p?<?0.0001) based on disintegration time.Conclusions
This method can be applied for pharmaceutical films for ranging indications as part of vigorous in vitro characterization. Parameters of the test can be altered based on site of application or indication.7.
Izabel Almeida Alves Keli Jaqueline Staudt Fernando Olinto Carreño Graziela de Araujo Lock Carolina de Miranda Silva Stela Maris Kuze Rates Teresa Dalla Costa Bibiana Verlindo De Araujo 《Pharmaceutical research》2018,35(7):132
Purpose
The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats.Method
The infection was induced by the administration of 100 μL of inoculum (1.105 CFU) through the tail vein. Free drug in the brain was assessed by microdialisys (μD). Blood and μD samples were collected at pre-determined time points up to 12 h after intravenous administration of FLC (20 mg/kg) to healthy and infected rats. The concentration-time profiles were analyzed by non-compartmental and population pharmacokinetics approaches.Results
A two-compartmental popPK model was able to simultaneously describe plasma and free drug concentrations in the brain for both groups investigated. Analysis of plasma and μD samples showed a better FLC distribution on the brain of infected than healthy animals (1.04?±?0.31 vs 0.69?±?0.14, respectively). The probability of target attainment was calculated by Monte Carlo simulations based on the developed popPK model for 125 mg/kg dose for rats and 400–2000 mg for humans.Conclusions
FLC showed a limited use in monotherapy to the treatment of criptoccocosis in rats and humans to value of MIC >8 μg/mL.8.
Maiara Cássia Pigatto Bibiana Verlindo de Araujo Bruna Gaelzer Silva Torres Stephan Schmidt Paolo Magni Teresa Dalla Costa 《Pharmaceutical research》2016,33(7):1657-1670
Purpose
This study aimed to determine free etoposide (ETO) concentrations in two regions of Walker-256 (W256) solid tumor using microdialysis and to establish a population pharmacokinetic (popPK) model to describe simultaneously free tumor and total plasma concentrations.Methods
W256 tumor-bearing Wistar rats received ETO 10 or 20 mg/kg i.v. bolus. Free ETO concentrations were sampled from central and peripheral regions of the tumor via CMA/20 probes for up to 7 h, whereas blood samples were collected via carotid artery cannulation. Total plasma and free tumor concentration-time profiles were analyzed by non-compartmental approach using WinNonlin® v. 5.3. PopPK modeling was conducted using MONOLIX v.4.3.3.Results
ETO penetration was higher in the periphery (61?±?15% and 61?±?29%) than in tumor center (34?±?6% and 28?±?11%) following 10 and 20 mg/kg doses, respectively (ANOVA, α?=?0.05). A 4-compartment model fitted ETO concentration-time profiles in all sampling compartments.Conclusions
The popPK model allowed the simultaneous fitting of plasma and tumor concentrations and a better understanding of ETO distribution in solid tumors. ETO plasma concentrations are not a good surrogate for tumoral exposure, emphasizing the importance of knowing intratumoral concentrations to predict drug response.9.
Sharon S. Y. Leung Thaigarajan Parumasivam Fiona G. Gao Nicholas B. Carrigy Reinhard Vehring Warren H. Finlay Sandra Morales Warwick J. Britton Elizabeth Kutter Hak-Kim Chan 《Pharmaceutical research》2016,33(6):1486-1496
Purpose
The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders.Method
A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1?=?60:20:20 and F2?=?40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed.Results
A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1?=?13.1?±?1.7?×?104 pfu and SD-F2?=?11.0?±?1.4?×?104 pfu) than from their counterpart SFD formulations (SFD-F1?=?8.3?±?1.8?×?104 pfu and SFD-F2?=?2.1?±?0.3?×?104 pfu).Conclusion
Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.10.
Pankaj K. Singh Anil K. Jaiswal Vivek K. Pawar Kavit Raval Animesh Kumar Himangsu K. Bora Anuradha Dube Manish K. Chourasia 《Pharmaceutical research》2018,35(3):60
Purpose
To fabricate, characterize and evaluate 3-O-sn-Phosphatidyl-L-serine (PhoS) anchored PLGA nanoparticles for macrophage targeted therapeutic intervention of VL.Materials and Methods
PLGA-AmpB NPs were prepared by well-established nanoprecipitation method and decorated with Phos by thin film hydration method. Physico-chemical characterization of the formulation was done by Zetasizer nano ZS and atomic force microscopy.Results
The optimized formulation (particle size, 157.3?±?4.64 nm; zeta potential, ? 42.51?±?2.11 mV; encapsulation efficiency, ~98%) showed initial rapid release up to 8 h followed by sustained release until 72 h. PhoS generated ‘eat-me’ signal driven augmented macrophage uptake, significant increase in in-vitro (with ~82% parasite inhibition) and in-vivo antileishmanial activity with preferential accumulation in macrophage rich organs liver and spleen were found. Excellent hemo-compatibility justified safety profile of developed formulation in comparison to commercial formulations.Conclusion
The developed PhoS-PLGA-AmpB NPs have improved efficacy, and necessary stability which promisingly put itself as a better alternative to available commercial formulations for optimized treatment of VL.11.
Wei Seng Wong Choy Sin Lee Hui Meng Er Wen Huei Lim 《Journal of pharmaceutical innovation》2017,12(1):76-89
Purpose
The aim of this work was to investigate the functional role of newly synthesised palm oil-based polyesteramide (POPEA) and stearic acid-based polyesteramide (SAPEA) in mefenamic acid (MA) solid dispersion (SD).Methods
Solid dispersions of MA were prepared by hot melt method, using a combination of POPEA/SAPEA as a polymer carrier. The effects of POPEA/SAPEA mixture ratio, drug loading percentage and influence of different Mw of POPEA (4000–17,000 Da) in SD were investigated. The SDs were characterised for drug content, solubility, dissolution behaviour and physico-chemical characteristics by DSC and FTIR. Comparisons were made with pure drug, physical mixture and a marketed MA formulation.Results
All SDs demonstrated faster dissolution rate than pure MA and SD 6 formulated with SAPEA/POPEA 4000 Da, 8:2 showed the highest T 50 release rate (45 min) with no significant difference (P?>?0.05) compared to marketed formulation. All SDs showed improved drug release (85.48?±?1.17 to 90.66?±?1.53%) against marketed formulation (81.30?±?1.26%) and MA (56.27?±?1.08%) after 6 h of dissolution. DSC endothermic peak for MA in SD 6 was broadened and shifted to lower temperature (194 °C). FTIR spectroscopy confirmed no chemical changes in MA SD, but establishment of hydrogen bonding between hydroxyl groups of PEA with amine groups of MA was observed by the red shift of OH band in SD samples. The SD was stable (P?>?0.05) at ambient condition for up to 90 days, reflecting by the drug content, dissolution profiles and solubility of the formulation.Conclusions
POPEA demonstrated surface lowering and wettability effects in improving the aqueous solubility and dissolution rate of MA in SD. The crystalline drug was transformed to amorphous formulation, via solubilisation and crystallisation inhibition effect of the PEA.12.
Juliana Damasceno Oliveira Lígia Nunes de Morais Ribeiro Gustavo Henrique Rodrigues da Silva Bruna Renata Casadei Verônica Muniz Couto Elizabeth Ferreira Martinez Eneida de Paula 《Pharmaceutical research》2018,35(12):229
Purpose
Etidocaine (EDC) is a long lasting local anesthetic, which alleged toxicity has restricted its clinical use. Liposomes can prolong the analgesia time and reduce the toxicity of local anesthetics. Ionic gradient liposomes (IGL) have been proposed to increase the upload and prolong the drug release, from liposomes.Methods
First, a HPLC method for EDC quantification was validated. Then, large unilamellar vesicles composed of hydrogenated soy phosphatidylcholine:cholesterol with 250 mM (NH4)2SO4 - inside gradient - were prepared for the encapsulation of 0.5% EDC. Dynamic light scattering, nanotracking analysis, transmission electron microscopy and electron paramagnetic resonance were used to characterize: nanoparticles size, polydispersity, zeta potential, concentration, morphology and membrane fluidity. Release kinetics and in vitro cytotoxicity tests were also performed.Results
IGLEDC showed average diameters of 172.3?±?2.6 nm, low PDI (0.12?±?0.01), mean particle concentration of 6.3?±?0.5?×?1012/mL and negative zeta values (?10.2?±?0.4 mV); parameters that remain stable during storage at 4°C. The formulation, with 40% encapsulation efficiency, induced the sustained release of EDC (ca. 24 h), while reducing its toxicity to human fibroblasts.Conclusion
A novel formulation is proposed for etidocaine that promotes sustained release and reduces its cytotoxicity. IGLEDC can come to be a tool to reintroduce etidocaine in clinical use.13.
Shaoqi Qu Cunchun Dai Fenfang Yang Tingting Huang Tianli Xu Li Zhao Yuwen Li Zhihui Hao 《Pharmaceutical research》2018,35(2):43
Purpose
The aim of this study was to prepare CEQ-loaded gelatin microspheres and compare two preparation methods, evaluate targeting to the lungs.Methods
Gelatin microspheres containing CEQ were prepared by an emulsion cross-linking method (ECLM) and a spray-drying method (SDM) and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release.Results
The microspheres prepared by ECLM gave a drug loading (DL) of 19.4?±?2.4% and an entrapment efficiency (EE) of 80.8?±?3.2%. The microspheres prepared by SDM resulted in a DL value of 20.8?±?2.7% and an EE of 95.3?±?3.8%. The average particle size of microspheres was 7-30 μm by both methods and both preparations sustained CEQ release for 36 h in the target tissue (lungs). The in vitro release profile of the microspheres matched the Korsmeyer-Peppas release pattern. In vivo studies identified the lung as the target tissue and the region of maximum CEQ release. Histopathological examination showed a partial lung inflammation that disappeared spontaneously as the microspheres were biodegraded. In general, the formulations were safe.Conclusion
The well-sustained CEQ release from the microspheres revealed its suitability as a drug delivery vehicle that minimized injury to healthy tissues while achieving the accumulation of therapeutic drug for lung targeting. The intravenous administration of CEQ gelatin microspheres prepared by SDM is of potential value in treating lung diseases in animals.14.
Shallu Kutlehria Imran Vhora Arvind Bagde Nusrat Chowdhury Gautam Behl Ketan Patel Mandip Singh 《Pharmaceutical research》2018,35(6):117
Purpose
Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG2000 conjugated with cholecalciferol (PEGCCF).Methods
Integrin targeted tacrolimus loaded PEGCCF micelles (TTM) were prepared by solvent diffusion evaporation method and characterized for particle size, osmolality, encapsulation efficiency and drug loading. Therapeutic potential of TTM was evaluated in benzalkonium chloride induced ocular inflammation model in BALB/c mice. Corneal flourescein staining and histopathological analysis of corneal sections was performed.Results
TTM had a particle size of 45.3?±?5.3 nm, encapsulation efficiency (88.7?±?0.9%w/w) and osmolality of 292–296 mOsmol/Kg. TTM significantly reduced the corneal fluorescence as compared to tacrolimus suspension (TACS). H&E staining showed that TTM could restore corneal epithelial thickness, reduce stromal edema (p?<?0.05) and decrease number of inflammatory cells (p?<?0.01) compared with TACS. Immunohistochemistry analysis demonstrated lower expression of Ki67?+?ve cells (p?<?0.05) and IL-6 throughout the cornea against TACS (p?<?0.01) and the control (p?<?0.001).Conclusions
TTM is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC.15.
Remo Holanda de Mendonça Furtado Robert Patrick Giugliano Celia Maria Cassaro Strunz Cyrillo Cavalheiro Filho José Antonio Franchini Ramires Roberto Kalil Filho Pedro Alves Lemos Neto Alexandre Costa Pereira Tânia Rúbia Rocha Beatriz Tonon Freire Elbio Antonio D’Amico José Carlos Nicolau 《Am J Cardiovasc Drugs》2016,16(4):275-284
Background
Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.Objectives
Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.Methods
We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12? (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).Results
We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] ?1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).Conclusions
Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.Clinical Trial Registration
NCT01896557.16.
Ghobad Mohammadi Amineh Shakeri Ali Fattahi Pardis Mohammadi Ali Mikaeili Alireza Aliabadi Khosro Adibkia 《Pharmaceutical research》2017,34(2):301-309
Purpose
Nystatin loaded PLGA and PLGA-Glucosamine nanoparticles were formulated. PLGA were functionalized with Glucosamine (PLGA-GlcN) to enhance the adhesion of nanoparticles to Candida Albicans (C.albicans) cell walls.Method
Quasi-emulsion solvent diffusion method was employed using PLGA and PLGA-GlcN with various drug–polymer ratios for the preparation of nanoparticles. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency and release properties. DSC, SEM, XRPD, 1H-NMR, and FT-IR were performed to analyze the physicochemical properties of the nanoparticles. Antifungal activity of the nanoparticles was evaluated by determination of MICs against C.albicans.Results
The spectra of 1H-NMR and FT-IR analysis ensured GlcN functionalization on PLGA nanoparticles. SEM characterization confirmed that particles were in the nanosize range and the particle size for PLGA and PLGA-GlcN nanoparticles were in the range of 108.63?±?4.5 to 168.8?±?5.65 nm and 208.76?±?16.85 nm, respectively. DSC and XRPD analysis ensured reduction of the drug crystallinity in the nanoparticles. PLGA-GlcN nanoparticles exhibit higher antifungal activity than PLGA nanoparticles.Conclusion
PLGA-GlcN nanoparticles showed more antifungal activity with appropriate physicochemical properties than pure Nystatin and PLGA nanoparticles.17.
Catiúscia P. Oliveira Willian A. Prado Vladimir Lavayen Sabrina L. Büttenbender Aline Beckenkamp Bruna S. Martins Diogo S. Lüdtke Leandra F. Campo Fabiano S. Rodembusch Andréia Buffon Adalberto PessoaJr Silvia S. Guterres Adriana R. Pohlmann 《Pharmaceutical research》2017,34(2):438-452
Purpose
This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors.Methods
Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined.Results
Bro-MLNC-Zn had z-average diameter of 135 nm and zeta potential of +23 mV. The complex is formed by a Zn-N chemical bond and a chelate with hydroxyl and carboxyl groups. Bromelain complexed at the nanocapsule surface maintained its proteolytic activity and showed anti-proliferative effect against human breast cancer cells (MCF-7) (72.6?±?1.2% at 1.250 μg mL?1 and 65.5?±?5.5% at 0.625 μg mL?1). Comparing Bro-MLNC-Zn and bromelain solution, the former needed a dose 160-folds lower than the latter for a similar effect. Tripan blue dye assay corroborated the results.Conclusions
The surface functionalization approach produced an innovative formulation having a much higher anti-proliferative effect than the bromelain solution, even though both in vitro proteolytic activity were similar, opening up a great opportunity for further studies in nanomedicine.18.
Purpose
Ruthenium complex is a potentially theranostic agent for cancer imaging and therapy, however its application is limited due to poor water-solubility and lack of tumor selectivity. To overcome the above drawbacks, pH-sensitive nanocapsule as a novel targeting carrier was designed to deliver ruthenium complex for treating xenograft tumor of mice.Methods
The core/shell structured nanocapsule with ruthenium complex tris(1,10-phenanthroline) ruthenium(II) complex (3P-Ru) as the core and a pH-sensitive polymeric material poly (2-diisopropylaminoethyl methacrylate)-block poly(2-aminoethyl methacrylate hydrochloride) (PbPS) as the shell was synthesized and characterized. Meanwhile, the nanocapsule was used to investigate cell viability and evaluate tissue distribution as well as preventing tumor growth efficacy in U251 stem cells tumor-bearing mouse model.Results
The nanocapsule had a size of 103.1?±?11.3 nm, zeta potential of -40?±?5.3 mV, EE of 76.7?±?0.9%, LE of 25.4?±?0.6% and it could control drug release under different pH conditions. The results of cell uptake showed that the fluorescent 3P-Ru loaded in the nanocapsule could be delivered into cells with high efficiency, and then significantly inhibited U251 proliferation in a concentration-dependent manner. After U251 stem cells were transplanted subcutaneously into mice, the 3P-Ru/PbPS nanocapsule (PbPS-Ru-NC) via intravenous administration could concentrate in tumor area and obviously prevent tumor growth.Conclusions
The pH-sensitive nanocapsule as a antitumor agent carrier was able to effectively deliver 3P-Ru into gliomas cells, and cell growth was significantly inhibited both in vitro and in vivo. Such pH-sensitive nanocapsule for ruthenium complex delivery would have great potential application in tumor theranostics.19.
Seyed Mostafa Monzavi Aida Alirezaei Zhaleh Shariati-Sarabi Jalil Tavakol Afshari Mahmoud Mahmoudi Banafsheh Dormanesh Faezeh Jahandoost Ali Reza Khoshdel Ali Etemad Rezaie 《Inflammopharmacology》2018,26(5):1175-1182
Background
Hydroxychloroquine (HCQ) is a widely prescribed medication to patients with systemic lupus erythematosus (SLE), with potential anti-inflammatory effects. This study was performed to investigate the efficacy of HCQ therapy by serial assessment of disease activity and serum levels of proinflammatory cytokines in SLE patients.Methods
In this prospective cohort study, 41 newly diagnosed SLE patients receiving 400 mg HCQ per day were included. Patients requiring statins and immunosuppressive drugs except prednisolone at doses lower than 10 mg/day were excluded. Outcome measures were assessed before commencement of HCQ therapy (baseline visit) as well as in two follow-up visits (1 and 2 months after beginning the HCQ therapy). Serum samples of 41 age-matched healthy donors were used as controls.Results
Median levels of IL-1β (p?<?0.001), IL-6 (p?=?0.001), and TNF-α (p?<?0.001) were significantly higher, whereas, median CH50 level was significantly lower (p?<?0.001) in SLE patients compared with controls. Two-month treatment with HCQ resulted in significant decrease in SLEDAI-2K (p?<?0.001), anti-dsDNA (p?<?0.001), IL-1β (p?=?0.003), IL-6 (p?<?0.001) and TNF-α (p?<?0.001) and a significant increase in CH50 levels (p?=?0.012). The reductions in SLEDAI-2K and serum levels of IL-1β and TNF-α were significantly greater in the first month compared with the reductions in the second month.Conclusion
HCQ therapy is effective on clinical improvement of SLE patients through interfering with inflammatory signaling pathways, reducing anti-DNA autoantibodies and normalizing the complement activity.20.
Chen EP Mahar Doan KM Portelli S Coatney R Vaden V Shi W 《Pharmaceutical research》2008,25(1):123-134