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1.
Anti-Neuroinflammatory Properties of n-3 Fatty Acids and Nano- Curcumin on Migraine Patients from Cellular to Clinical Insight: A Randomized, Double-Blind and Placebo-Controlled Trial.
Honarvar, NM, Soveid, N, Abdolahi, M, Djalali, M, Hatami, M, Karzar, NH
Endocrine, metabolic & immune disorders drug targets. 2021;(2):365-373
Abstract
BACKGROUND AND OBJECTIVES Migraine is an exhausting neuro-inflammatory disorder recognized as recurrent headache attacks. Evidence has shown that Interleukin (IL)-1β plays a substantial role in the neuro-immunity pathogenicity of migraine. n-3 fatty acids and curcumin revealed neuromodulatory and anti-inflammatory effects through several pathways, of which the suppression of IL-1β gene expression is an important inflammatory pathway. The aim of this study was the investigation of synergistic relation of n -3 fatty acids and nano-curcumin on IL-1β gene expression and serum levels in migraine patients. METHODS This study was performed as a randomized, double-blind, placebo-controlled trial in a period of two months. A total of 80 episodic migraines were assigned into 4 groups of 1) n-3 fatty acids and curcumin combination; 2) n -3 fatty acids; 3) nano-curcumin; and 4) n-3 fatty acids and curcumin placebo. The gene expression and serum level of IL-1β were measured by real-time PCR and ELISA methods respectively, at the beginning and the end of the interventions. RESULTS Results showed the n-3 fatty acids and nano-curcumin combination significantly reduced the attack frequency in a synergistic status (P < 0.001). A significantly greater reduction in the serum level of IL-1β was observed in the combination group, and the differences in the other groups were not statistically significant. The IL-1β gene expression in the combination group showed a significant reduction for other treatment groups (P < 0.05), but these significant differences were absent after multiple testing Bonferroni corrections. CONCLUSION Present findings revealed that n -3 fatty acids and curcumin co-supplementation can be suggested as a promising new approach in migraine headache management, but further studies are needed to confirm these findings.
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2.
Application of Nanocarbon in Breast Approach Endoscopic Thyroidectomy Thyroid Cancer Surgery.
Ma, JJ, Zhang, DB, Zhang, WF, Wang, X
Journal of laparoendoscopic & advanced surgical techniques. Part A. 2020;(5):547-552
Abstract
Objective: This study aimed to investigate the application of nanocarbon in surgical endoscopy in patients with thyroid cancer for the clinical tracing of level VI sentinel lymph nodes (SLNs) and for parathyroid gland protection. Materials and Methods: Ninety-three patients with papillary thyroid carcinoma (PTC) who underwent an endoscopic thyroid cancer operation were included. We randomly divided these patients into a control group (n = 42) and a nanocarbon group (n = 51). For the nanocarbon group, after thyroid exposure, nanocarbon was injected into the thyroid gland, and the SLNs were resected and subjected to frozen sectioning and routine pathological examination. In addition, the postoperative calcium and parathyroid hormone (PTH) levels of both groups were analyzed to compare the features of the nanocarbon application. Results: The number of central lymph (level VI) nodes dissected and the number of metastatic lymph nodes identified were analyzed in both groups. The number of dissected lymph nodes from both unilateral and bilateral thyroid surgeries was significantly larger in the nanocarbon group than in the control group. At the same time, the number of identified metastasis lymph nodes dissected were higher in the nanocarbon group than in the control group. We assessed the postoperative calcium and PTH level to evaluate the parathyroid function. Our results show that the nanocarbon group had a better protective effect on parathyroid function than the control group. Conclusions: As a lymph node trace agent, nanocarbon could better evaluate and permit a more clear lymph dissection for patients with PTC. Nanocarbon contributes to a decrease in the incidence rate of parathyroid damage, which has great clinical value.
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3.
Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states.
Litou, C, Patel, N, Turner, DB, Kostewicz, E, Kuentz, M, Box, KJ, Dressman, J
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2019;:105031
Abstract
INTRODUCTION When developing bio-enabling formulations, innovative tools are required to understand and predict in vivo performance and may facilitate approval by regulatory authorities. EMEND® is an example of such a formulation, in which the active pharmaceutical ingredient, aprepitant, is nano-sized. The aims of this study were 1) to characterize the 80 mg and 125 mg EMEND® capsules in vitro using biorelevant tools, 2) to develop and parameterize a physiologically based pharmacokinetic (PBPK) model to simulate and better understand the in vivo performance of EMEND® capsules and 3) to assess which parameters primarily influence the in vivo performance of this formulation across the therapeutic dose range. METHODS Solubility, dissolution and transfer experiments were performed in various biorelevant media simulating the fasted and fed state environment in the gastrointestinal tract. An in silico PBPK model for healthy volunteers was developed in the Simcyp Simulator, informed by the in vitro results and data available from the literature. RESULTS In vitro experiments indicated a large effect of native surfactants on the solubility of aprepitant. Coupling the in vitro results with the PBPK model led to an appropriate simulation of aprepitant plasma concentrations after administration of 80 mg and 125 mg EMEND® capsules in both the fasted and fed states. Parameter Sensitivity Analysis (PSA) was conducted to investigate the effect of several parameters on the in vivo performance of EMEND®. While nano-sizing aprepitant improves its in vivo performance, intestinal solubility remains a barrier to its bioavailability and thus aprepitant should be classified as DCS IIb. CONCLUSIONS The present study underlines the importance of combining in vitro and in silico biopharmaceutical tools to understand and predict the absorption of this poorly soluble compound from an enabling formulation. The approach can be applied to other poorly soluble compounds to support rational formulation design and to facilitate regulatory assessment of the bio-performance of enabling formulations.
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4.
Phonopheresis Associated with Nanoparticle Gel from Phyllanthus amarus Relieves Pain by Reducing Oxidative Stress and Proinflammatory Markers in Adults with Knee Osteoarthritis.
Decha, P, Kanokwan, K, Jiraporn, T, Pichaya, J, Pisittawoot, A
Chinese journal of integrative medicine. 2019;(9):691-695
Abstract
OBJECTIVE To determine the changes in serum levels of inflammatory biomarkers and antioxidant levels among the knee osteoarthritis (OA) patients after treatment with Phyllanthus amarus (PP) by nanoparticle gel phonophoresis. METHODS This study was a randomized, double-blind, placebo-control, parallel-group, clinical trial involving 30 subjects with mild-to-moderate degree of knee OA. The patients were allocated to two groups using a computer-generated random numbers, and received conventional ultrasound therapy (control group, 15 cases) and PP (treatment group, 15 cases) once daily for 10 sessions. The pain was evaluated by visual analogue scale (VAS). Serum levels of tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbnent assay (ELISA). Nitric oxide (NO) was determined by modified Griess reagent. The antioxidant effects, including superoxide dismutase (SOD) and total antioxidant capacity (TAC), were also measured by ELISA assay. RESULTS The VAS score was significantly decreased in the treatment group compared with the control group after treatment (P<0.01). The serum concentrations of TNF-α and NO were significantly reduced in the treatment group compared with the control group (P<0.01) after treatment. However, the serum concentrations of SOD and TAC in the treatment group were significantly higher after treatment compared with the control group (P<0.01). CONCLUSION PP could alleviate knee pain and significantly reduce systemic anti-inflammatory effects in knee OA patients.
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5.
NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.
Bonvalot, S, Rutkowski, PL, Thariat, J, Carrère, S, Ducassou, A, Sunyach, MP, Agoston, P, Hong, A, Mervoyer, A, Rastrelli, M, et al
The Lancet. Oncology. 2019;(8):1148-1159
Abstract
BACKGROUND Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING Nanobiotix SA.
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Nano curcumin supplementation reduced the severity of diabetic sensorimotor polyneuropathy in patients with type 2 diabetes mellitus: A randomized double-blind placebo- controlled clinical trial.
Asadi, S, Gholami, MS, Siassi, F, Qorbani, M, Khamoshian, K, Sotoudeh, G
Complementary therapies in medicine. 2019;:253-260
Abstract
BACKGROUND Diabetic Sensorimotor Polyneuropathy (DSPN) is a common complication of diabetes mellitus. Curcumin is the most important ingredient found in turmeric which has a very high potential for eliminating free radicals and inhibiting oxidative stress as an antioxidant agent. The aim of this study was to determine the effect of Nano-curcumin supplementation on the severity of sensorimotor polyneuropathy in patients with Type 2 diabetes mellitus (T2DM). METHOD This parallel, double-blind randomized, placebo-controlled clinical trial was conducted on 80 diabetic patients. Participants were allocated randomly to the intervention (n = 40) and the control group (n = 40). They received 80 mg of nano-curcumin or placebo capsules for 8 weeks. Anthropometric measurements, dietary intake, physical activity, glycemic indices and the severity of DSPN were measured before and after the intervention. RESULT Supplementation of nano curcumin was accounted for a significant reduction in Glycated hemoglobin(HbA1c) (p < 0.001) and Fast Blood Sugar(FBS) (p = 0.004), total score of neuropathy (p < 0.001), total reflex score (p = 0.04) and temperature (p = 0.01) compared to placebo group. CONCLUSION Our findings indicated that curcumin supplementation for 2 months improved and reduced the severity of DSPN in patients with T2DM.
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7.
Progesterone-loaded nanosized transethosomes for vaginal permeation enhancement: formulation, statistical optimization, and clinical evaluation in anovulatory polycystic ovary syndrome.
Salem, HF, Kharshoum, RM, Abou-Taleb, HA, AbouTaleb, HA, AbouElhassan, KM
Journal of liposome research. 2019;(2):183-194
Abstract
Bio-identical progesterone (PRG) is an exogenous female steroidal hormone which is used for treatment of polycystic ovary syndrome (PCOS). However, it suffers from poor bioavailability due to hepatic metabolism and poor solubility. The target of this work was to evaluate and statistically optimize PRG-loaded nanovesicle transethosomes (NVTEs) based in mucoadhesive gel for transvaginal delivery of PRG as potential luteal-phase support. A 24 full factorial design was used to explore the effect of phosphatidylcholine (PC), Tween 80, cetyltrimethyl ammonium bromide and ethanol concentration on particle size, entrapment efficiency (EE%), % in vitro PRG release after 24 h and transvaginal flux. PRG-loaded NVTEs were prepared by injection sonication method. The results revealed that the mean particle sizes ranged from 133.3 ± 3.42 to 349.5 ± 1.24 nm, zeta potential ranged from -23.5 ± 3.84 to +74.6 ± 4.97 mV, EE% ranged from 87.93 ± 3.58 to 97.05 ± 2.61%, % PRG release ranged from 50.9 ± 2.75 to 90.69 ± 2.07 and transvaginal flux ranged from 0.274 ± 0.03 to 0.531 ± 0.04 mg/cm2/h. The optimized formulation was subjected to transmission electron microscope for morphological examination and then incorporated in the mucoadhesive vaginal gel using Carbopol 974, hydroxyl propyl methylcellulose and sodium alginate. The optimized formulation was clinically studied in anovulatory PCOS and showed a significant increase in the serum PRG, endometrial thickness, echogenicity degree and the pregnancy rate. Briefly, PRG-loaded NVTEs vaginal gel might be a promising formulation for luteal phase support and increase pregnancy rate in anovulatory PCOS.
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8.
An evaluation and comparison of the efficacy of nanocrystalline calcium sulfate bone grafts (NanoGen) and medical-grade calcium sulfate bone grafts (DentoGen) in human extraction sockets.
Kumari, B, Gautam, DK, Horowitz, RA, Jain, A, Mahajan, A
Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995). 2014;(10):e36-41
Abstract
BACKGROUND Grafting a fresh extraction socket is essential for successful regeneration of bone and maximizing volume preservation. Various synthetic grafts have been used to simulate bone formation. The purpose of the present study was to evaluate clinical, histomorphometric, and radiographic healing at 1-month, 3-month, and 4-month time points after tooth extraction with placement of calcium sulfate hemihydrate putty bone grafts NanoGen and DentoGen to determine their efficacy in ridge preservation following tooth extraction. METHOD Sixty subjects who were in need of extraction were recruited. The subjects were randomly assigned their group based on computer software for both the test groups (NanoGen and DentoGen). DentoGen is a medical-grade calcium sulfate hemihydrate with particle of 30 µm, and NanoGen is a nanocrystalline version of DentoGen with particle size 400 µm to 800 µm. Data were recorded at 1, 3, and 4 months after extraction socket grafting. Bone biopsies were taken at 4 months for histomorphometric analysis. RESULTS The mean percentage of bone formed by NanoGen was 51.19 ± 9.53% and by DentoGen 50.67 ± 16.16% after 4 months. No statistically significant difference was noted in the mean bone formation by NanoGen and DentoGen at various time intervals; no bone graft remnants of DentoGen were found at 4 months. The mean percentage of bone graft remnants left after 4 months for NanoGen was 6.83 ± 16% in the maxilla and 7.38 ± 21% in the mandible. The mean percentage of soft tissue formed was significantly higher with DentoGen in mandibular socket sites. On radiographic evaluation the mean percentage of socket fill with DenoGen was found to be 23.1 ± 11.65%, 50 ± 9.6%, and 76.7 ± 11% and with NanoGen was 29.2 ± 12.8%, 52.8 ± 15.6%, and 76.47 ± 12.43% at 1 month, 3 months, and 4 months postoperative intervals, respectively. CONCLUSION Both the materials investigated in the study showed excellent bone forming capacity, but the nanocrystalline version (NanoGen) of calcium sulfate was found to have clinical and biologic advantages over DentoGen.
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A multicenter phase II randomized study of Cremophor-free polymeric nanoparticle formulation of paclitaxel in women with locally advanced and/or metastatic breast cancer after failure of anthracycline.
Ranade, AA, Bapsy, PP, Nag, S, Raghunadharao, D, Raina, V, Advani, SH, Patil, S, Maru, A, Gangadharan, VP, Goswami, C, et al
Asia-Pacific journal of clinical oncology. 2013;(2):176-81
Abstract
AIMS: Paclitaxel is extensively used in the treatment of advanced carcinomas of the breast, ovary and non-small cell lung cancer. In clinical use it is formulated in the non-ionic surfactant polyethoxylated castor oil (Cremophor) and dehydrated alcohol to enhance drug solubility. Cremophor adds to toxic effects of paclitaxel by producing or contributing to the well-described hypersensitivity reactions that commonly occur during its infusion, affecting a large number of patients. This randomized trial was conducted to evaluate efficacy and safety of novel nanoparticle-based paclitaxel in the treatment of patients with advanced breast cancer. METHOD Patients were randomized to receive either nanoparticle paclitaxel (NP) 300 mg/m(2) , (NP300) or NP220 mg/m(2) or Cremophor paclitaxel 175 mg/m(2) (CP 175). NP was administered as a 1-h infusion without premedication and CP as a 3-h infusion with premedication every 3 weeks. RESULTS In total, 194 patients who had been administered at least one dose were included for safety analysis and 170 patients who completed at least two cycles of therapy were analyzed for efficacy. NP showed an overall response rate (complete response + partial response) of 40% in the NP220 and NP300 arms as compared to 31% in the CP arm. The incidence of neutropenia (all grades) was lowest in the NP220 arm (39.4%) compared to the NP300 (55%) and CP arm (50%). CONCLUSION NP is well tolerated and can be safely administered without any premedication in comparison to conventional paclitaxel, which requires the use of premedication before administration. NP demonstrates promising efficacy with a favorable safety profile.
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10.
Effect of nanoscale topography of titanium implants on bone vessel network, osteocytes, and mineral densities.
Traini, T, Murmura, G, Piattelli, M, Scarano, A, Pettinicchio, M, Sinjari, B, Caputi, S
Journal of periodontology. 2013;(10):e40-7
Abstract
BACKGROUND Chemical and physical properties of an implant surface have a major influence on the structure of peri-implant bone and thus may influence the clinical performance of the implant. This study aims to evaluate the bone microstructure around implants with and without added nanometer-sized calcium phosphate particles. METHODS An implant with dual acid-etched surface (control) and an implant with dual acid-etched surface and CaP nanoparticles (test) were placed in the posterior maxilla of 15 patients. Bone microstructure was evaluated for osteocyte density (OD), bone vessel volume density (BVVD), and bone mineral density (BMD). RESULTS BVVD was 1.806 ± 0.05 for test implants and 1.533 ± 0.10 for control implants (P <0.001). BMDlow was 17.4 × 10(4) µm(2) for test implants and 15.0 × 10(4) µm(2) for control implants (P = 0.025). Results from the BMDhigh comparison, test versus control, were not statistically significant (P >0.05). OD was 575.6 ± 63.7 mm(2) for test implants and 471.2 ± 61.9 mm(2) for control implants (P <0.001). CONCLUSIONS After 8 weeks of healing, the bone microstructure around test implants appeared to be significantly more organized. Clinical implications of these results include shortened healing time and indication for earlier loading protocols.