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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
NCT01896557.2.
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Jasmine A. Luzum Kevin M. Sweet Philip F. Binkley Tara J. Schmidlen Joseph P. Jarvis Michael F. Christman Wolfgang Sadee Joseph P. Kitzmiller 《Pharmaceutical research》2017,34(8):1615-1625
Purpose
This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure.Methods
Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n?=?65) or metoprolol (n?=?33).Results
CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02–0.75] p?=?0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84–10.30] p?=?0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day).Conclusion
Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.5.
Urszula Cibor Małgorzata Krok-Borkowicz Monika Brzychczy-Włoch Łucja Rumian Krzysztof Pietryga Dominika Kulig Wojciech Chrzanowski Elżbieta Pamuła 《Pharmaceutical research》2017,34(10):2075-2083
Purpose
To develop polysaccharide-based membranes that allow controlled and localized delivery of gentamicin for the treatment of post-operative bone infections.Methods
Membranes made of gellan gum (GUM), sodium alginate (ALG), GUM and ALG crosslinked with calcium ions (GUM + Ca and ALG + Ca, respectively) as well as reference collagen (COL) were produced by freeze-drying. Mechanical properties, drug release, antimicrobial activity and cytocompatibility of the membranes were assessed.Results
The most appropriate handling and mechanical properties (Young’s modulus, E = 92 ± 4 MPa and breaking force, F MAX = 2.6 ± 0.1 N) had GUM + Ca membrane. In contrast, COL membrane showed F MAX = 0.14 ± 0.02 N, E = 1.0 ± 0.3 MPa and was deemed to be unsuitable for antibiotic delivery. The pharmacokinetic data demonstrated a uniform and sustainable delivery of gentamicin from GUM + Ca (44.4 ± 1.3% within 3 weeks), while for COL, ALG and ALG + Ca membranes the most of the drug was released within 24 h (55.3 ± 1.9%, 52.5 ± 1.5% and 37.5 ± 1.8%, respectively). Antimicrobial activity against S. aureus and S. epidermidis was confirmed for all the membranes. GUM + Ca and COL membranes supported osteoblasts growth, whereas on ALG and ALG + Ca membranes cell growth was reduced.Conclusions
GUM + Ca membrane holds promise for effective treatment of bone infections thanks to favorable pharmacokinetics, bactericidal activity, cytocompatibility and good mechanical properties.6.
McCluskey SA Cheung WK Katznelson R Poonawala H Fedorko L Djaiani G Mehta B Karkouti K 《European journal of clinical pharmacology》2009,65(3):273-279
Background
In anticipation of future studies, we examined the pharmacokinetics profile of erythropoietin (EPO) in patients undergoing cardiac surgery.Methods
Cardiac surgical patients were enrolled into one of six groups: four cardiopulmonary bypass (CPB) groups [placebo (n?=?6), 250 IU/kg EPO (n?=?3), 500 IU/kg EPO (n =?3), and 500 IU/kg EPO, two doses (n =?6)] and two off-pump coronary artery bypass (OPCAB) groups [placebo (n?=?3) and 500 IU/kg EPO (n?=?3)]. The EPO was administered prior to anesthesia and 10 min after CPB (if required). Blood samples for serum EPO were collected at baseline, 10 min after dosing, 5 min after sternotomy, during CPB or the equivalent for OPCAB (5, 15, 45, 60 min), and post-CPB (5, 15, 45, and 60 min, 6, 12 and 24 h, and daily until day 5).Results
Endogenous EPO increased within 24 h of surgery in the placebo group and remained elevated. There was approximately a 40% decrease in serum EPO concentration at the initiation of CPB due to an increase in circulatory blood volume. There were no differences in apparent volume of distribution in the plasma (Vc) (42.2?±?9.9, 39.8?±?6.3, 42.3?±?14.0 mL/kg), clearance (CL) (4.63?±?1.14, 3.44?±?0.68, 4.27?±?0.52 mL h/kg), and t½ (16.4?±?8.0 16.9?±?10.6, 22.4?±?9.3 h) between the CPB treatment groups. The pharmacokinetic profile of EPO in the OPCAB group was similar to that for the CPB groups: Vc = 39.3?±?7.0 mL/kg, CL = 4.98?±?0.17 mL h/kg and t½ = 17.1?±?18.1 h.Conclusions
CPB had no apparent effect on the pharmacokinetics of EPO.7.
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.8.
Jonathan T. Su Ryan S. Teller Priya Srinivasan Jining Zhang Amy Martin Samuel Sung James M. Smith Patrick F. Kiser 《Pharmaceutical research》2017,34(10):2163-2171
Purpose
Design of intravaginal rings (IVRs) for delivery of antiretrovirals is often guided by in vitro release under sink conditions, based on the assumption that in vivo release will follow a similar release profile.Methods
We conducted a dose-ranging study in the female reproductive tract of pigtail macaques using matrix IVRs containing IQP-0528, a poorly soluble but highly potent antiretroviral drug with an IC90 of 146 ng/mL. These IVRs consisted of drug-loaded segments, 15.6% IQP-0528 in Tecoflex 85A, comprising either all, half, or a quarter of the entire ring.Results
In vitro release under sink conditions demonstrates loading-proportional release, with a cumulative 30-day release of 48.5 ± 2.2 mg for our 100% loaded ring, 24.8 ± .36 mg from our 50% loaded ring, and 13.99 ± 1.58 mg from our 25% loaded ring. In vivo, while drug concentration in vaginal fluid is well in excess of IQP-0528’s EC90, we find no statistical difference between the different ring loadings in either swab drug levels or drug released from our rings.Conclusions
We show that in vitro release may not accurately reflect in vivo release, particularly for poorly soluble drugs. All tested loadings of our IVRs are capable of delivering IQP-0528 well in excess of the IC90.9.
Nicholas B. Carrigy Rachel Y. Chang Sharon S. Y. Leung Melissa Harrison Zaritza Petrova Welkin H. Pope Graham F. Hatfull Warwick J. Britton Hak-Kim Chan Dominic Sauvageau Warren H. Finlay Reinhard Vehring 《Pharmaceutical research》2017,34(10):2084-2096
Purpose
To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices.Methods
Phage D29 lysate was amplified to a titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify phage titer.Results
Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose.Conclusions
Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.10.
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.11.
Seema Upadhyay Iliyas Khan Avinash Gothwal Praveen K. Pachouri N. Bhaskar Umesh D. Gupta Devendra S. Chauhan Umesh Gupta 《Pharmaceutical research》2017,34(9):1944-1955
Purpose
First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF.Methods
HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1H–NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC’s interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis.Results
Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, ?19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p < 0.01, INH Vs PMRI; p < 0.0001, RIF Vs PMRI), respectively. MABA assay (cytotoxicity) based MIC values of PMRI formulation was observed as ≥0.0625 and ≥0.50 μg/mL (for sensitive and resistant strain). The microscopic analysis further confirmed that the delivery approach was effective than pure drugs.Conclusions
RIF loaded and INH conjugated HPMA-PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.12.
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.13.
Hala Bakr El-Nassan Aliaa Nabil ElMeshad Walaa Wadie Rabab H. Sayed 《Pharmaceutical research》2018,35(8):149
Purpose
To assess the gelation power of N-palmitoyl L-alanine derivatives in injectable oils and to use the best chosen organogel as parenteral implant of granisetron for the treatment of emesis.Methods
Twelve N-palmitoyl L-alanine derived organogels were developed and evaluated in terms of morphology, thermal properties and in vivo performance. The ability of the selected formula to form in situ gel upon subcutaneous injection in rats and its biocompatibility were monitored over 2 weeks by histopathological examination of the injection site.Results
The acid derivative (N-palmitoyl L-alanine; PA) was superior to ester derivatives. The chosen formula (PA/safflower oil 10% w/v) was successful in forming an in situ gel of granisetron when subcutaneously injected in rats, lasting for 2 weeks and proved to be biocompatible by histopathological examination. Moreover, it exerted an extended antiemetic activity by decreasing the cisplatin-induced pica for a duration of 96 h and reduced preprotachykinin A mRNA expression and Substance P level for up to 4 days (gastric tissue) or 5 days (medulla oblongata) in rats.Conclusion
Granisetron organogel could be considered as a safe, sustained-release and supportive anticancer treatment in both acute and chronic emesis as well as an accompanying treatment with chemotherapeutics in cancer cases.14.
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.15.
Sarinj Fattah Abhijit Babaji Shinde Maja Matic Myriam Baes Ron H. N. van Schaik Karel Allegaert Celine Parmentier Lysiane Richert Patrick Augustijns Pieter Annaert 《Pharmaceutical research》2017,34(6):1309-1319
Purpose
OCT1/3 (Organic Cation Transporter-1 and -3; SLC22A1/3) are transmembrane proteins localized at the basolateral membrane of hepatocytes. They mediate the uptake of cationic endogenous compounds and/or xenobiotics. The present study was set up to verify whether the previously observed variability in OCT activity in hepatocytes may be explained by inter-individual differences in OCT1/3 mRNA levels or OCT1 genotype.Methods
Twenty-seven batches of cryopreserved human hepatocytes (male and female, age 24–88 y) were characterized for OCT activity, normalized OCT1/3 mRNA expression, and OCT1 genetic mutation. ASP+ (4-[4-(dimethylamino)styryl]-N-methylpyridinium iodide) was used as probe substrate.Results
ASP+ uptake ranged between 75 ± 61 and 2531 ± 202 pmol/(min × million cells). The relative OCT1 and OCT3 mRNA expression ranged between 0.007–0.46 and 0.0002–0.005, respectively. The presence of one or two nonfunctional SLC22A1 alleles was observed in 13 batches and these exhibited significant (p = 0.04) association with OCT1 and OCT3 mRNA expression. However, direct association between genotype and OCT activity could not be established.Conclusion
mRNA levels and genotype of OCT only partially explain inter-individual variability in OCT-mediated transport. Our findings illustrate the necessity of in vitro transporter activity profiling for better understanding of inter-individual drug disposition behavior.16.
Deepanshu Shilpi Varun Kushwah Ashish Kumar Agrawal Sanyog Jain 《Pharmaceutical research》2017,34(7):1505-1516
Purpose
The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles.Method
AT loaded stearic acid modified gelatin nanoparticles (AT-MG NPs) were prepared via two-step desolvation method with extensive optimization of different process variables. Further, the developed nanoparticles where evaluated against in vitro Caco-2 cell model and in vivo bioavailability.Results
Extensive optimization of nanoformulation resulted into the formation of AT-MG NPs with particle size 247.7 ± 10.9 nm, PDI 0.219 ± 0.07, and entrapment efficiency 58.7 ± 5.3%. Freeze dried nanoparticles were found to have spherical shape as determined by SEM and demonstrated excellent stability in simulated gastrointestinal conditions and during storage. Developed nanoparticles exhibited sustained release up to 24 h and remarkably higher Caco-2 cell uptake. Mechanistic studies further revealed the clathrin and caveolae mediated endocytosis as principle mechanism. In line with Caco-2 cell uptake observations, AT-MG NPs showed ~4.84-fold increase in the AUC0-∞ values of AT in comparison with free AT following oral administration.Conclusion
Overall, the stearic acid conjugated gelatin NPs demonstrates a promising potential in improving the drug payload of BCS class II drugs and enhancing oral bioavailability.17.
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.18.
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.19.
Liisa M. Hirvonen Gilbert O. Fruhwirth Nishanthan Srikantha Matthew J. Barber James E. Neffendorf Klaus Suhling Timothy L. Jackson 《Pharmaceutical research》2016,33(8):2025-2032
Purpose
To measure the hydrodynamic radii of intravitreal anti-VEGF drugs ranibizumab, aflibercept and bevacizumab with μs time-resolved phosphorescence anisotropy.Methods
Ruthenium-based dye Ru(bpy)2(mcbpy???O???Su???ester)(PF6)2, whose lifetime of several hundred nanoseconds is comparable to the rotational correlation time of these drugs in buffer, was used as a label. The hydrodynamic radii were calculated from the rotational correlation times of the Ru(bpy)2(mcbpy???O???Su???ester)(PF6)2-labelled drugs obtained with time-resolved phosphorescence anisotropy measurements in buffer/glycerol solutions of varying viscosity.Results
The measured radii of 2.76±0.04 nm for ranibizumab, 3.70±0.03 nm for aflibercept and 4.58±0.01 nm for bevacizumab agree with calculations based on molecular weight and other experimental measurements.Conclusions
Time-resolved phosphorescence anisotropy is a relatively simple and straightforward method that allows experimental measurement of the hydrodynamic radius of individual proteins, and is superior to theoretical calculations which cannot give the required accuracy for a particular protein.20.
Eduardo Celia Palma Nelson Guardiola Meinhardt Airton Tetelbom Stein Isabela Heineck Maria Isabel Fischer BibianaVerlindo de Araújo Teresa Dalla Costa 《Pharmaceutical research》2018,35(6):116