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1.
Peng Zhu Zhi Ye Dong Guo Zongping Xiong Shiqiong Huang Jun Guo Wei Zhang James E. Polli Honghao Zhou Qing Li Yan Shu 《Pharmaceutical research》2018,35(12):243
Purpose
The organic cation transporters (OCTs) and multidrug and toxin extrusions (MATEs) together are regarded as an organic cation transport system critical to the disposition and response of many organic cationic drugs. Patient response to the analgesic morphine, a characterized substrate for human OCT1, is highly variable. This study was aimed to examine whether there is any organic cation transporter-mediated drug and drug interaction (DDI) between morphine and commonly co-administrated drugs.Methods
The uptake of morphine and its inhibition by six drugs which are commonly co-administered with morphine in the clinic were assessed in human embryonic kidney 293 (HEK293) cells stably expressing OCT1, OCT2 and MATE1. The in vivo interaction between morphine and the select irinotecan was determined by comparing the disposition of morphine in the absence versus presence of irinotecan treatment in mice.Results
The uptake of morphine in the stable HEK293 cells expressing human OCT1 and OCT2 was significantly increased by 3.56 and 3.04 fold, respectively, than that in the control cells, with no significant uptake increase in the cells expressing human MATE1. All of the six drugs examined, including amitriptyline, fluoxetine, imipramine, irinotecan, ondansetron, and verapamil, were inhibitors of OCT1/2-mediated morphine uptake. The select irinotecan significantly increased the plasma concentrations and decreased hepatic and renal accumulation of morphine in mice.Conclusions
Morphine is a substrate of OCT1 and OCT2. Clinician should be aware that the disposition of and thus the response to morphine may be altered by co-administration of an OCT1/2 inhibitor, such as irinotecan.2.
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
NCT01896557.3.
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.4.
Guangqing Xiao Christopher Rowbottom Carri Boiselle Liang-Shang Gan 《Pharmaceutical research》2018,35(8):159
Purpose
The renal clearance of fampridine (Fampyra®, or Ampyra®) significantly exceeds the glomerular filtration rate, suggesting active renal secretion is likely the major elimination pathway. The goal of this study was to identify the renal transporters that are involved in the renal active secretion, and elucidate the active renal secretion mechanism of fampridine.Methods
The uptake of fampridine to HEK-293 cells overexpressing human OCT2, MATE1 or MATE2K was determined in the absence and presence of Cimetidine, the prototypical inhibitor of the transporters. The inhibition potential of fampridine on the renal transporters was evaluated by determining the uptake of TEA and Metformin, the probe substrates of the transporters of OCT2 and MATEs, respectively, in the absence or presence of fampridine.Results
Significant time- and concentration-dependent uptake of fampridine by human OCT2 was observed. The Km and Vmax were determined as 51.0?±?17.1 μM and 1107?±?136 pmole/min/106 cells, respectively. Fampridine also inhibited OCT2 mediated uptake of Metformin with estimated IC50 of 66.8 μM. In contrast, there was not significant uptake of fampridine by human MATE1 or MATE2K, and fampridine did not inhibit MATE1 or MATE2K mediated uptake of TEA.Conclusion
The studies indicated fampridine is a substrate and inhibitor of OCT2, but not MATE1 or MATE2K. Results from the study suggested the active renal secretion of fampridine is mediated by human OCT2 but not MATE1 or MATE2K. To our knowledge, fampridine is the first reported substrate specific to OCT2 but not to MATE1 or MATE2K.5.
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
Purpose
To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling.Methods
A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation.Results
CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA?≥?90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%).Conclusions
Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.6.
Purpose
FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs (hsa-miR-3181 and hsa-miR-3136-3p) acting on FCGRT.Methods
The binding of candidate microRNAs to the 3′-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells. The effect of microRNAs on FCGRT mRNA and FcRn protein expression was evaluated using specific microRNA mimics and inhibitor transfections in A549, HEK293 and HepG2 cells.Results
Hsa-miR-3181 mimic reduced luciferase reporter activity by 70.1% (10 nM, P <?0.0001). In A549, HEK293 and HepG2 cells, hsa-miR-3181 decreased FCGRT mRNA expression (48.6%, 51.3% and 43.5% respectively, 25 nM, P <?0.05). The hsa-miR-3181 mimic decreased the expression of FcRn protein by 40% after 48 h (25 nM, P <?0.001). The mature form of hsa-miR-3181 was detected in samples of human liver.Conclusions
These data suggest that hsa-miR-3181 is an epigenetic regulator of FCGRT expression. The identification of this regulator of FCGRT may provide insights into a potential determinant of interindividual variability in FcRn expression.7.
Rationale
Inhibition of the glycine transporter 1 (GlyT1) activity increases extra-cellular glycine availability in the CNS. At glutamatergic synapses, increased binding to the glycine-B site located in the N-methyl-d-aspartate receptor (NMDAR) can enhance neurotransmission via NMDARs. Systemic treatment of 2-chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734), a selective GlyT1 inhibitor, is effective against social recognition impairment induced by neonatal phencyclidine treatment and enhances pre-pulse inhibition in a mouse strain (DBA/2) with intrinsic sensorimotor gating deficiency, suggesting that SSR504734 may be an effective cognitive enhancer.Objective
The objective of the study was to examine if SSR504734 exhibits a promnesic effect on working memory function in wild-type C57BL/6 mice using an automatic continuous alternation task.Materials and methods
Hungry mice were trained to alternate their nose pokes between two food magazines across successive discrete trials in an operant chamber in order to obtain food reward. Correct choice on a given trial thus followed a non-matching or win-shift rule in relation to the preceding trial, with manipulation of the demand on memory retention, by varying the delay between successive trials.Results
Pre-treatment with SSR504734 (30 mg/kg, i.p.) improved choice accuracy when the delay from the previous trial was extended to 12–16 s. Furthermore, a dose–response analysis (3, 10, 30 mg/kg) revealed a clear dose-dependent efficacy of the drug: 3 mg/kg was without effect, whilst 10 mg/kg led to an intermediate enhancement in performance.Conclusion
The present findings represent the first demonstration of the promnesic effects of SSR504734 under normal physiological conditions, lending further support to the suggestion of its potential as a cognitive enhancer.8.
Yu Takahashi Tomohiro Nishimura Kei Higuchi Saki Noguchi Yuma Tega Toshiki Kurosawa Yoshiharu Deguchi Masatoshi Tomi 《Pharmaceutical research》2018,35(12):246
Purpose
The anti-epileptic drug pregabalin crosses the blood-brain barrier (BBB) in spite of its low lipophilicity. This study was performed to determine whether L-type amino acid transporters (LAT1/SLC7A5 and LAT2/SLC7A8) contribute to the uptake of pregabalin.Methods
Pregabalin uptake by LATs-transfected HEK293 cells or hCMEC/D3 cells, an in vitro human BBB model, was measured by LC-MS/MS analysis. Expression of LAT1 mRNA in hCMEC/D3 cells was determined by quantitative RT-PCR analysis.Results
Overexpression of LAT1, but not LAT2, in HEK293 cells significantly increased the cellular uptake of pregabalin, and the LAT1-mediated uptake was saturable with a Km of 0.288 mM. LAT1-mediated amino acid uptake was inhibited specifically and almost completely in the presence of 1 mM pregabalin. The uptake of pregabalin by hCMEC/D3 cells was sodium-independent, saturable (Km?=?0.854 mM), and strongly inhibited by large amino acids at 1 mM, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, a specific system L inhibitor, at 1 mM and by JPH203, a LAT1-selective inhibitor, at 10 μM. Pregabalin uptake in hCMEC/D3 cells was also decreased by 75% by the silencing of LAT1 gene using LAT1 siRNA.Conclusions
Our results indicate that LAT1, but not LAT2, recognizes pregabalin as a substrate. It is suggested that LAT1 mediates pregabalin transport at the BBB.9.
Charlotte L. Kvasnovsky Ingvar Bjarnason Ana Nora Donaldson Roy A. Sherwood Savvas Papagrigoriadis 《Inflammopharmacology》2017,25(5):499-509
Background
Diverticular disease is a significant burden on healthcare systems that is managed, surgically or medically, mainly as an emergency or acute condition. There are no standardized treatment recommendations for symptomatic uncomplicated disease. We hypothesized that a probiotic would reduce abdominal pain in such patients.Methods
We conducted a single-center, double-blind, placebo-controlled trial of probiotic treatment (Symprove) in adult patients with moderate-to-severe chronic, non-acute symptomatic diverticular disease. 143 patients were randomized to receive 1 mL/kg/day of probiotic liquid (N = 72) or placebo (N = 71) daily for 3 months. The primary endpoint was abdominal pain severity. Secondary endpoints consisted of the change in the frequency of eight abdominal symptoms and the level of intestinal inflammation (fecal calprotectin).Results
120 patients completed the trial. Abdominal pain score, the primary end point, decreased in both groups, but no significant difference between the groups was found (P = 0.11). In relation to placebo, the probiotic significantly decreased the frequency of four of the eight secondary endpoints: constipation, diarrhea, mucorrhea, and back pain (P < 0.04). No significant differences were found in frequency of abdominal pain, PR bleeding, dysuria, and bloating.Conclusions
Multi-strain liquid probiotic did not improve abdominal pain scores significantly, but significantly improved the frequency of four other symptoms associated with chronic, non-acute symptomatic diverticular disease.10.
Jesper Østergaard Emil Meng-Lund Susan Weng Larsen Claus Larsen Karsten Petersson James Lenke Henrik Jensen 《Pharmaceutical research》2010,27(12):2614-2623
Purpose
This study was conducted to characterize UV imaging as a platform for performing in vitro release studies using Nicorette® nicotine patches as a model drug delivery system.Methods
The rate of nicotine release from 2 mm diameter patch samples (Nicorette®) into 0.067 M phosphate buffer, pH 7.40, was studied by UV imaging (Actipix SDI300 dissolution imaging system) at 254 nm. The release rates were compared to those obtained using the paddle-over-disk method.Results
Calibration curves were successfully established which allowed temporally and spatially resolved quantification of nicotine. Release profiles obtained from UV imaging were in qualitative agreement with results from the paddle-over-disk release method.Conclusion
Visualization as well as quantification of nicotine concentration gradients was achieved by UV imaging in real time. UV imaging has the potential to become an important technology platform for conducting in vitro drug release studies.11.
Issey Takehara Takashi Yoshikado Keiko Ishigame Daiki Mori Ken-ichi Furihata Nobuaki Watanabe Osamu Ando Kazuya Maeda Yuichi Sugiyama Hiroyuki Kusuhara 《Pharmaceutical research》2018,35(7):138
Purpose
To evaluate association of the dose-dependent effect of rifampicin, an OATP1B inhibitor, on the plasma concentration–time profiles among OATP1B substrates drugs and endogenous substrates.Methods
Eight healthy volunteers received atorvastatin (1 mg), pitavastatin (0.2 mg), rosuvastatin (0.5 mg), and fluvastatin (2 mg) alone or with rifampicin (300 or 600 mg) in a crossover fashion. The plasma concentrations of these OATP1B probe drugs, total and direct bilirubin, glycochenodeoxycholate-3-sulfate (GCDCA-S), and coproporphyrin I, were determined.Results
The most striking effect of 600 mg rifampicin was on atorvastatin (6.0-times increase) and GCDCA-S (10-times increase). The AUC0–24h of atorvastatin was reasonably correlated with that of pitavastatin (r2?=?0.73) and with the AUC0–4h of fluvastatin (r2?=?0.62) and sufficiently with the AUC0–24h of rosuvastatin (r2?=?0.32). The AUC0–24h of GCDCA-S was reasonably correlated with those of direct bilirubin (r2?=?0.74) and coproporphyrin I (r2?=?0.80), and sufficiently with that of total bilirubin (r2?=?0.30). The AUC0–24h of GCDCA-S, direct bilirubin, and coproporphyrin I were reasonably correlated with that of atorvastatin (r2?=?0.54–0.70).Conclusion
These results suggest that direct bilirubin, GCDCA-S, and coproporphyrin I are promising surrogate probes for the quantitative assessment of potential OATP1B-mediated DDI.12.
Bonnie Williams Eleni Tsangari Romany Stansborough Victor Marino Melissa Cantley Anak Dharmapatni Rachel Gibson Egon Perilli Tania Crotti 《Inflammopharmacology》2017,25(1):55-68
Objective
To investigate the effect of caffeic acid phenethyl ester (CAPE) on local and systemic inflammation and bone loss in collagen antibody-induced arthritis (CAIA) mice.Methods
Four groups of mice (n = 8 per group) were allocated; control, CAPE (1 mg/kg), CAIA and CAIA + CAPE (1 mg/kg). Local inflammation and bone loss were evaluated using clinical paw scores, in vivo micro-computed tomography (micro-CT), histological assessment and tartrate-resistant acid phosphatase (TRAP) staining. Serum levels of C-reactive protein (CRP) and C-terminal telopeptide (CTX-1) were measured by ELISA. Jejunum and colon sections were evaluated histopathologically for damage and toxicity.Results
Greater paw scores and percentage change in paw volume were observed in CAIA + CAPE compared to the control groups (p < 0.05). Bone volume over time remained unchanged (p = 0.94) and the number of multinucleated TRAP-positive cells was greatest in CAIA + CAPE mice (p < 0.05). CRP and CTX-1 levels did not differ between groups. CAIA + CAPE mice exhibited lower colon toxicity scores and a reduced percentage of cavitated goblet cells in the colon crypts compared with CAIA mice (p = 0.026 and p = 0.003, respectively). Histopathology in the jejunum was not altered.Conclusion
CAPE did not reduce paw inflammation or bone loss in CAIA mice. CAPE reduced histopathological changes in the colon of CAIA mice.13.
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 IC90.14.
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.15.
Purpose
4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB.Methods
The brain transport of 4-PBA across the BBB was investigated following intravenous (IV) injection and internal carotid artery perfusion (ICAP) in vivo. The mechanism of transport was examined using TR-BBB cells, an in vitro model of the BBB.Results
The volume of distribution (VD) of 4-PBA by rat brain was about 7-fold greater than that of sucrose, a BBB impermeable vascular space marker, suggesting the blood-to-brain transport of 4-PBA through the BBB in the physiological state. [14C]4-PBA uptake by TR-BBB cells showed time-, pH- and concentration-dependence with a K m of 13.4 mM at pH 7.4 and 3.22 mM at pH 6.0. The uptake was Na+ independent, and was significantly inhibited by alpha-cyano-4-hydroxycinnamate (a typical inhibitor for monocarboxylate transport), endogenous monocarboxylate compounds and monocarboxylic drugs. Lactate and valproate competitively inhibited [14C]4-PBA uptake with K i value of 13.5 mM and 7.47 mM, respectively. These results indicate the role of monocarboxylate transporters (MCTs) in 4-PBA transport into the brain at the BBB. TR-BBB cells expressed mRNA of rMCT1, 2, and 4, especially, rMCT1 showed high mRNA expression level. In addition, [14C]4-PBA uptake was inhibited by rMCT1 specific small interfering RNA.Conclusion
The transport mechanism of 4-PBA from blood to brain across the BBB likely involves MCT1.16.
Sadikali F. Sayyad Bibhu P. Panda Sanjay R. Chaudhari 《Journal of pharmaceutical innovation》2016,11(1):102-108
Purpose
Utilization of traditional medicines increased worldwide. However, lack of modern technology creates problems for rejection of such preparations. Good manufacturing practices (GMPs) advocate uniformity and stability in the development of modern pharmaceuticals. Implementation of appropriate formulation strategies may enhance regulatory acceptance of complementary medicines. Herewith an attempt has been made to identify the impact of process parameter temperature, pH, and yeast cell number (inoculum volume) on manufacturing of ayurvedic fermented cardiotonic—arjunarishta.Method
Optimization of the selected three process parameters was carried out for maximum production of alcohol in arishta using Box–Behnken design of response surface methodology with support of Design Expert software. Alcohol produced in formulation was detected after solvent extraction by dichromate oxidation method.Result
Quadratic model was found significant with sum of squares 86.76 and F value 250.60. The incubation temperature 33.33 °C, pH 4.73, and inoculum volume 3.25 ml (4?×?107 yeast cells/ml) have been identified as the best for maximal production of alcohol. It shows 7.68 % (v/v) production of alcohol which is identified by dichromate oxidation method. Presence of gallic acid also detected in optimized formulation by HPTLC with concentration 0.296 % (w/v).Conclusion
This kind of study will definitely make formulation of arishta easier with higher consistency; moreover, manufacturing is possible in any season at any place.17.
Junzeng Fu Bart V. J. Cuppen Paco M. J. Welsing Herman van Wietmarschen Amy C. Harms Ruud Berger Slavik Koval Ruth D. E. Fritsch-Stork Johannes W. J. Bijlsma Thomas Hankemeier Jan van der Greef 《Inflammopharmacology》2016,24(6):397-402
Objective
As there are pharmacological differences between males and females, and glucocorticoid (GC) treatment is associated with increased cardiovascular mortality rate in rheumatoid arthritis (RA) patients, it is important to study serum polar lipid profiles of male and female patients in response to GC therapy. Gender differences may require an adjustment to the treatment strategy for a selection of patients.Methods
Serum samples from 281 RA patients were analysed using a targeted lipidomics platform. The differences in GC use and gender on polar lipid profiles were cross sectionally examined by multiple linear regressions, while correcting for confounding factors.Results
Differences in polar lipids between GC users and non-GC users in females and males were merely restricted to lysophospholipids (lysophosphatidylcholines and lysophosphatidylethanolamines). Lysophospholipids in female patients treated with GCs were significantly higher than female patients not treated with GCs (p = 6.0 E?6), whereas no significant difference was observed in male GC users versus non-users (p = 0.397).Conclusion
The lysophospholipid profiles in response to GCs were significantly different between male and female RA patients, which may have implications for the cardiovascular risk of GC treatment.18.
Juan Zhao Zhuoya Wan Chuchu Zhou Qin Yang Jianxia Dong Xu Song Tao Gong 《Pharmaceutical research》2018,35(10):196
Purpose
The aim of this study was to design hyaluronic acid (HA) layer-by-layer (LbL) nanoparticles, which carried paclitaxel (PTX) and Indocyanine green (ICG) to both tumor cells and tumor associated cells to achieve synergistic chemo-photothermal therapeutic effect.Methods
The LbL-engineered nanoparticles (PDIH) were prepared by dopamine self-polymerization on PTX nanocrystal to form thin, surface-adherent polydopamine (PDA) films, which subsequently absorbed ICG and HA. The tumor cell and tumor associated cell targeting and antitumor efficacy of PDIH were investigated both in vitro an in vivo using 4 T1 murine mammary cancer cell lines and mice bearing orthotopic 4 T1 breast tumor.Results
PDIH presented a long-rod shape in TEM and showed enhanced photothermal effect and cytotoxicity upon NIR laser irradiation both in vitro and in vivo. PDIH also displayed high target ability to CD44 overexpressed tumor cells and tumor associated cells mediated by HA. In vivo antitumor study indicated that PDIH therapeutic strategy could achieve remarkable antitumor efficacy.Conclusion
PDIH showed excellent tumor-targeting property and chemo-photothermal therapeutic efficacy.19.
Leonard Y. Chu Ling Ye Ke Dong Richard W. Compans Chinglai Yang Mark R. Prausnitz 《Pharmaceutical research》2016,33(4):868-878
Purpose
This study tested the hypothesis that encapsulation of influenza vaccine in microneedle patches increases vaccine stability during storage at elevated temperature.Methods
Whole inactivated influenza virus vaccine (A/Puerto Rico/8/34) was formulated into dissolving microneedle patches and vaccine stability was evaluated by in vitro and in vivo assays of antigenicity and immunogenicity after storage for up to 3 months at 4, 25, 37 and 45°C.Results
While liquid vaccine completely lost potency as determined by hemagglutination (HA) activity within 1–2 weeks outside of refrigeration, vaccine in microneedle patches lost 40–50% HA activity during or shortly after fabrication, but then had no significant additional loss of activity over 3 months of storage, independent of temperature. This level of stability required reduced humidity by packaging with desiccant, but was not affected by presence of oxygen. This finding was consistent with additional stability assays, including antigenicity of the vaccine measured by ELISA, virus particle morphological structure captured by transmission electron microscopy and protective immune responses by immunization of mice in vivo.Conclusions
These data show that inactivated influenza vaccine encapsulated in dissolving microneedle patches has enhanced stability during extended storage at elevated temperatures.20.
Yanhui Chao Yuheng Liang Guihua Fang Haibing He Qing Yao Hang Xu Yinrong Chen Xing Tang 《Pharmaceutical research》2017,34(3):610-618