Suchergebnisse

Selvakani Prabakaran,1 Mariappan Rajan,1 Changwei Lv,2 Guolin Meng3 1Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India; 2Department of Orthopaedics, The Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an 710018, Mainland China; 3Orthopaedic Department of Xijing Hospital of the Fourth Military Medical University, Xi'an, Shaanxi, 710032, Mainland ChinaCorrespondence: Changwei Lv Department of OrthopaedicsThe Affiliated Hospital of Northwest University, Xi'an No.3 Hospital, Xi'an 710018, Mainland ChinaEmail lucwei76@sina.comPurpose: To develop the surface-treated metal implant with highly encouraged positive properties, including high anti-corrosiveness, bio-activeness and bio-compatibleness for orthopedic applications.Methods: In this work, the surface of commercially pure titanium (Ti) metal was treated with bio-compatible polydopamine (PD) by merely immersing the Ti plate in PD solution. The composite of trivalent lanthanide minerals (La3+, Ce3+ and Gd3+)-substituted hydroxyapatite (MHAP) with Aloe vera (AV) gel was prepared and coated on the PD-Ti plate by electrophoretic deposition (EPD) method. The choice of trivalent lanthanide ions is based on their bio-compatible nature and bone-seeking properties. The formation of the PD layer, composites, and composite coatings on Ti plate and PD-Ti surface was confirmed by FT-IR, XRD, SEM and HR-TEM observations. In-vitro assessments such as osteoblasts like MG-63 cell viability, alkaline phosphatase activity and mineralization ability of the MHAP/AV composite were tested, and the composite-coated plate was implanted into a rat bone defect model for in-vivo bone regeneration studies.Results: The coating ability of the MHAP/AV composite was highly preferred to PD-treated Ti plate than an untreated Ti plate due to the metal absorption ability of PD. This was confirmed by SEM analysis. The in-vitro and in-vivo studies show the better osteogenic ability of MHAP/AV composite at 14th day and 4th week of an experimental period, respectively.Conclusion: The osteoblast ability of the fabricated device without producing any adverse effect in the rat model recommends that the fabricated device would serve as a better platform on the hard tissue regeneration for load-bearing applications of orthopedics.Keywords: bio-compatible, electrophoretic deposition, hydroxyapatite, mussel adhesive protein, polydopamine, surface treatment

Lin Zhao, 1 Omer Mustapha, 2 Shumaila Shafique, 2 Talha Jamshaid, 3 Fakhar ud Din, 4 Yasir Mehmood, 5 Khaleeq Anwer, 6 Qurrat ul Ain Yousafi, 7 Talib Hussain, 8 Ikram Ullah Khan, 5 Muhammad Usman Ghori, 9 Yasser Shahzad, 8 Abid Mehmood Yousaf 8 1Department of Rheumatology of Traditional Chinese and Western Medicine, Xinxiang Central Hospital, Xinxiang 453000, People's Republic of China; 2Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 74200, Pakistan; 3Faculty of Pharmacy and Alternative Medicine, Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; 4Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38040, Pakistan; 6Office of Chief Executive Officer, District Health Authority, Pakpattan 57400, Pakistan; 7Department of Neurosurgery, District Headquarters Hospital, Rawalpindi 46000, Pakistan; 8Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan; 9Department of Pharmacy, School of Applied Science, University of Huddersfield, Huddersfield HD1 3DH, UKCorrespondence: Abid Mehmood Yousaf; Talib Hussain Tel +92-300-477-4147; +92-345-722-0536Email abid.ucp@hotmail.com Email talib.hussain@cuilahore.edu.pkBackground: Piroxicam exhibits low oral bioavailability, due to its meager solubility in water. The intent of this study was to ameliorate the bioavailability of the drug by employing a solubility-enhancing encapsulation technique.Methods: Seven samples were formulated with piroxicam and gelatin using both solvent evaporation and electrospraying together. Evaluation of solubility and release rate in water and assessment of bioavailability in rats were carried out in comparison with piroxicam plain drug powder (PPDP). Other in vitro explorations were accomplished using powder X-ray diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy.Results: All piroxicam-loaded gelatinnanocontainers (PLGNs) enhanced solubility and release of the payload in water. In particular, a PLGN formulation consisting of piroxicam and gelatin at a 1:8 (w:w) ratio presented about 600-fold the drug solubility of that shown by PPDP. Moreover, 85.12%± 10.96% of the payload was released from this formulation in 10 minutes which was significantly higher than that dissolved from PPDP in 10 minutes (11.81%± 5.34%). Drug content, drug loading, and encapsulation efficiency of this formulation were 93.41%± 0.56%, 10.45%± 0.06%, and 66.74%± 6.87%, respectively. The drug loaded in PLGNs existed in the amorphous state, as confirmed by X-ray diffraction and differential scanning–calorimetry analyses, and was more stable when analyzed by thermogravimetric analysis. Moreover, Fourier-transform infrared spectroscopy analysis suggested nonexistence of any piroxicam–gelatin interaction in the formulation. In the scanning electron–microscopy image, PLGNs appeared as round, smooth particles, with particle size of < 1,000 nm. Amelioration in bioavailability of piroxicam with the aforementioned PLGN formulation was fourfold that of PPDP.Conclusion: The PLGN formulation fabricated with piroxicam and gelatin at 1:8 (w:w) might be a promising system for enhanced biopharmaceutical performance of the drug.Keywords: aqueous solubility, electrospraying, gelatin encapsulation, nanocontainers, oral bioavailability, piroxicam

Yang Wang,1 Wen Song,2 Yi Cui,3 Yang Zhang,1 Shenglin Mei,4 Qintao Wang1 1State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Air Force Medical University, Xi'an, People's Republic of China; 2State Key Laboratory of Military Stomatology, Department of Prosthetic Dentistry, School of Stomatology, Air Force Medical University, Xi'an, People's Republic of China; 3Equipment Department, Xijing Hospital, Air Force Medical University, Xi'an, People's Republic of China; 4Department of Prosthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, People's Republic of ChinaCorrespondence: Qintao WangDepartment of Periodontology, School of Stomatology, Air Force Medical University, No. 145 West Changle Road, Xi'an 710032, People's Republic of ChinaTel +86 2984 776 096Fax +0086 2983 223 047Email yznmbk@fmmu.edu.cnPurpose: Reducing toxicity, immunogenicity, and costs of small interfering RNAs (siRNA) carrier materials are key goals for RNA interference (RNAi) technology transition from bench to bed. Recently, calcium ions (Ca2+) have garnered attention as a novel, alternative material for delivering siRNA to cells. However, the tolerance for Ca2+ concentration varies in different cell types, which has limited its applications in vivo. Bovine serum albumin (BSA) can bind to Ca2+ through chelation. Moreover, BSA is a favorable coating material for nanoparticles owing to its excellent biocompatibility. Therefore, we hypothesized that coating Ca2+-siRNA with BSA helps buffer Ca2+ toxicity in vivo.Methods: BSA-Ca2+-siRNA nanoparticles were prepared, and the size, shape, encapsulation, and release efficiency were characterized using atomic force microscopy, scanning electronic microcopy, and gel electrophoresis. Binding nanoparticles were evaluated using attenuated total reflection-Fourier-transform infrared spectroscopy. The cellular uptake, intracellular release, cytotoxicity, and gene knockdown of nanoparticles were evaluated in periodontal ligament stem cells (PDLSCs) using laser-scanning confocal microscope, flow cytometry, and real-time quantitative polymerase chain reaction.Results: BSA and Ca2+-siRNA could form a stable nano-scale complex (∼ 140 nm in diameter). The nanocomplexes could maintain siRNA release for more than 1 week in neutral phosphate-buffered saline (PBS) and could induce accelerated degradation in acidic PBS (pH 5.0). The nanoparticles were taken up by the cells, primarily through macropinocytosis, and were then released intracellularly through the acidification of endosomes/lysosomes. Importantly, the BSA-Ca2+ carrier had high transfection efficiency and biocompatibility both in vitro and in vivo. To demonstrate the therapeutic potential of our BSA coating-optimized Ca2+-siRNA technology, we showed that BSA-Ca2+-siWWP1 complexes strongly enhanced the osteogenic differentiation of inflammatory PDLSCs.Conclusion: BSA-Ca2+ could potentially be used for siRNA delivery, which is not only highly efficient and cost-effective but also biocompatible to host tissues owing to the BSA coating.Keywords: bovine serum albumin, calcium ions, osteogenic differentiation, small interfering RNA

Qudsia Tabassam,1 Tahir Mehmood,1,2 Abdul Rauf Raza,1 Azmat Ullah,3 Farhan Saeed,4 Faqir Muhammad Anjum5 1Department of Chemistry, University of Sargodha, Sargodha, Pakistan; 2Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences-UVAS, Lahore, Pakistan; 3Department of Food Science and Human Nutrition, University of Veterinary and Animal Sciences-UVAS, Lahore, Pakistan; 4Institute of Home & Food Sciences, Government College University Faisalabad, Faisalabad, Pakistan; 5Vice Chancellor Secretariat, University of the Gambia, Banjul, The GambiaCorrespondence: Tahir Mehmood; Faqir Muhammad Anjum Email tahir.mehmoodbiochem@uvas.edu.pk; dranjum@utg.edu.gmBackground: Nanotechnology is gaining emerging interest in advanced drug discovery therapeutics due to their tremendous properties including enhanced delivery of therapeutic payload, extensive surface to volume ratio, high permeability, retention behaviors, etc. The gold nanoparticles (AuNPs) are favored due to their advanced features, such as biogenic, tunable physiochemical response, ease in synthesis, and wide range of biomedical applications. The phytochemicals have been focused to design Au nano-carrier-based conjugation for active-targeting drug delivery due to their nano conjugation ability.Aim: The present study describes the facile synthesis of 20nm spherical AuNPs and their conjugation with reported anti-cancer phytocompound Withanolide-A (1).Methods: The 20nm sAuNPs were synthesized chemically and characterized their phytochemical gold nanoconjugates through UV-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging techniques. The anti-cancer therapeutic potentials were tested with both nanoconjugates and pure WithanolideA (1) by using SKBR3 breast cancer cells line.Results: The synthesized sAuNPs showed significant conjugation with Withanolide-A and showed stability. Furthermore, these Au nanoconjugates with Withanolide-A (1) significantly induce blockage of SKBR3 cell growth at half maximal active concentration that compared to pure Withanolide-A (1).Conclusion: Our findings provide a foundation to further progress how they can overcome cancer drug resistance by conjugating active drugs in combination with AuNPs through optimizing the effective drug concentration and removing the surface barrier.Keywords: Withania somnifera, Withanolide-A, gold nanoparticle; AuNP, breast cancer, anti-cancer and incucyte

Jie Gao,1,2,* Xiaohan Chen,1,* Tianjun Ma,1,* Bin He,1 Peng Li,1 Yucheng Zhao,1 Yuejin Ma,1 Jianhua Zhuang,1 You Yin1 1Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People's Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai 200444, People's Republic of China*These authors contributed equally to this workCorrespondence: You Yin; Jianhua ZhuangDepartment of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People's Republic of ChinaTel/Fax +86-21-63586818Email yinyou179@163.com; jianhuazh11@126.comPurpose: Alzheimer's disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid β protein (Aβ) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line.Methods: Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10– 20 nm in size and had nearly neutral zeta potential.Results: The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy.Conclusion: In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.Keywords: Alzheimer's disease, autophagosomes, lysosome, nano-carrier, autophagic flux

Menka Khoobchandani, 1, 2 Kavita K Katti, 1, 2 Alice Raphael Karikachery, 1, 2 Velaphi C Thipe, 1, 2 Deepak Srisrimal, 3 Darsha Kumar Dhurvas Mohandoss, 3 Rashmi Dhurvas Darshakumar, 3 Chintamani M Joshi, 3 Kattesh V Katti 1, 2, 4 1Department of Radiology, University of Missouri, Columbia, MO 65212, USA; 2Institute of Green Nanotechnology, University of Missouri, Columbia, MO 65212, USA; 3Dhanvantari Nano Ayushadi Pvt Ltd, Chennai 600017, India; 4Department of Physics, Department of Pharmacology, Department of Biological Engineering, University of Missouri Research Reactor (MURR), University of Missouri, Columbia, MO 65212, USACorrespondence: Kattesh V KattiDepartment of Radiology, University of Missouri, One Hospital Drive, Columbia, MO 65212 USATel +1 573 882-5656Email KattiK@health.missouri.eduPurpose: The overarching objective of this investigation was to investigate the intervention of green nanotechnology to transform the ancient holistic Ayurvedic medicine scientifically credible through reproducible formulations and rigorous pre-clinical/clinical evaluations.Methods: We provide, herein, full details: (i) on the discovery and full characterization of gold nanoparticles-based Nano Swarna Bhasma (henceforth referred to as NSB drug); (ii) In vitro anti-tumor properties of NSB drug in breast tumor cells; (iii) pre-clinical therapeutic efficacy studies of NSB drug in breast tumor bearing SCID mice through oral delivery protocols and (iv) first results of clinical translation, from mice to human breast cancer patients, through pilot human clinical trials, conducted according to the Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (abbreviated as AYUSH) regulatory guidelines of the Government of India in metastatic breast cancer patients.Results: The preclinical in vitro and in vivo investigations, in breast tumor bearing mice, established unequivocally that the NSB Nano-Ayurvedic medicine-gold nanoparticles-based drug is highly effective in controlling the growth of breast tumors in a dose dependent fashion in vivo. These encouraging pre-clinical results prompted us to seek permission from the Indian Government's holistic medicine approval authority, AYUSH, for conducting clinical trials in human patients. Patients treated with the NSB drug capsules along with the "standard of care treatment" (Arm B) exhibited 100% clinical benefits when compared to patients in the treatment Arm A, thus indicating the tremendous clinical benefits of NSB drug in adjuvant therapy.Conclusion: We have succeeded in clinically translating, from mice to humans, in using proprietary combinations of gold nanoparticles and phytochemicals to develop the Nano-Ayurvedic drug: Nano Swarna Bhasma (NSB), through innovative green nanotechnology, for treating human metastatic breast cancer patients.Keywords: gold nanoparticles, mangiferin, mango peel, Nano Swarna Bhasma, NSB, triple negative breast tumor, pilot clinical

Jianbo Gao, 1 Bing Xia, 1 Shengyou Li, 1 Liangliang Huang, 2 Teng Ma, 1 Xiaowei Shi, 1 Kai Luo, 3 Yujie Yang, 1 Laihe Zhao, 1 Hao Zhang, 4 Beier Luo, 5 Jinghui Huang 1 1Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China; 2Department of Orthopaedics, The General Hospital of Central Theater Command of People's Liberation Army, Wuhan, People's Republic of China; 3Department of Orthopaedics, The 985th Hospital of the PLA Joint Logistics Support Force, Taiyuan, People's Republic of China; 4Department of Spinal Surgery, People's Hospital of Longhua District, Shenzhen, People's Republic of China; 5Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China*These authors contributed equally to this workCorrespondence: Beier LuoDepartment of Orthopaedics, Changhai Hospital, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of ChinaTel/Fax +862131161700Email bear_luo@126.comJinghui HuangDepartment of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 169 Changle West Road, Xi'an, Shaanxi 710032, People's Republic of ChinaTel/Fax +862984775275Email huangjh@fmmu.edu.cnPurpose: The clinical outcome of spinal cord injury is usually poor due to the lack of axonal regeneration and glia scar formation. As one of the most classical supporting cells in neural regeneration, Schwann cells (SCs) provide bioactive substrates for axonal migration and release molecules that regulate axonal growth. However, the effect of SC transplantation is limited by their poor migration capacity in the astrocyte-rich central nervous system.Methods: In this study, we first magnetofected SCs with chondroitinase ABC-polyethylenimine functionalized superparamagnetic iron oxide nanoparticles (ChABC/PEI-SPIONs) to induce overexpression of ChABC for the removal of chondroitin sulfate proteoglycans. These are inhibitory factors and forming a dense scar that acts as a barrier to the regenerating axons. In vitro, we observed the migration of SCs in the region of astrocytes after the application of a stable external magnetic field.Results: We found that magnetofection with ChABC/PEI-SPIONs significantly up-regulated the expression of ChABC in SCs. Under the driven effect of the directional magnetic field (MF), the migration of magnetofected SCs was enhanced in the direction of the magnetic force. The number of SCs with ChABC/PEI-SPIONs migrated and the distance of migration into the astrocyte region was significantly increased. The number of SCs with ChABC/PEI-SPIONs that migrated into the astrocyte region was 11.6- and 4.6-fold higher than those observed for the intact control and non-MF groups, respectively. Furthermore, it was found that SCs with ChABC/PEI-SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF.Conclusion: The mobility of the SCs with ChABC/PEI-SPIONs was enhanced along the axis of MF, holding the potential to promote nerve regeneration by providing a bioactive microenvironment and relieving glial obstruction to axonal regeneration in the treatment of spinal cord injury.Keywords: Schwann cells, astrocytes, magnetic field, superparamagnetic iron oxide nanoparticles, spinal cord injury, cell orientation

Ru Sun, 1 Chengwu Shen, 1 Shumaila Shafique, 2 Omer Mustapha, 2 Talib Hussain, 3 Ikram Ullah Khan, 4 Yasir Mehmood, 4 Khaleeq Anwer, 5 Yasser Shahzad, 3 Abid Mehmood Yousaf 3 1Department of Pharmacy, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250000, People's Republic of China; 2Faculty of Pharmaceutical Sciences, Dow College of Pharmacy, Dow University of Health Sciences, Karachi 74200, Pakistan; 3Department of Pharmacy, COMSATS University Islamabad, Lahore 54000, Pakistan; 4Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan; 5Office of Chief Executive Officer, District Health Authority, Pakpattan 57400, PakistanCorrespondence: Abid Mehmood Yousaf; Talib HussainDepartment of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54000, PakistanTel +92-300-4774147; +92-345-7220536Email abid.ucp@hotmail.com; talib.hussain@cuilahore.edu.pkBackground: Bezafibrate is a BCS class II drug as it presents very low solubility in water; therefore, its bioavailability after oral administration is very poor. The aim of this work was to enhance solubility and dissolution rate of bezafibrate in water in order to enhance its oral bioavailability.Methods: Several formulations were prepared using PVP K30 and Cremophor ELP employing the solvent-evaporation method and the electrospraying technique. Solubility, release rate, bioavailability in male Sprague Dawley rats, and lipid profile attributes in Wistar rats were assessed in comparison with bezafibrate plain powder. Solid-state characterization was carried out using X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM).Results: All the formulations exerted positive effect towards the desired goal. In particular, the optimized formulation furnished about 14-fold enhanced solubility and 85.48 ± 10.16% drug was released in 10 min as compared with bezafibrate alone (4.06 ± 2.59%). The drug existed in the amorphous state in the prepared sample as confirmed by XRD and DSC, whilst no drug-excipient interactions were observed through FTIR analysis. Moreover, SEM revealed smooth-surfaced spherical particles of the optimized formulation. A 5.5-fold higher oral bioavailability was achieved with the optimized formulation in comparison with bezafibrate plain powder. Also, TG, LDL and TC were decreased, and HDL was increased considerably in HFD-treated rats.Conclusion: The optimized formulation consisting of bezafibrate, PVP K30 and cremophor ELP (1/12/1.5, w/w/w) might be a capable drug delivery system for orally administering poorly water-soluble bezafibrate with improved bioavailability and antihyperlipidemic effects.Keywords: aqueous solubility, bezafibrate, electrospraying, lipid profile, oral bioavailability, solid dispersion

Zhong Wan1 ,* Fangyuan Xie2 ,* Liang Wang,3 Guoqing Zhang,2 Hai Zhang3 1Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, People's Republic of China; 2Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, Tong Ji University School of Medicine, Shanghai 201204, People's Republic of China*These authors contributed equally to this workCorrespondence: Guoqing ZhangDepartment of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of ChinaTel/ Fax +86-21-81875571Email guoqing_zhang91@126.comHai ZhangDepartment of Pharmacy, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, People's Republic of ChinaTel/ Fax +86 21-20261401Email zhxdks2005@126.comPurpose: Cabazitaxel (CBZ) is a new taxane-based antitumor drug approved by the FDA for the treatment of prostate cancer, especially for patients with advanced prostate cancer for whom docetaxel is ineffective or causes aggravation. However, Tween 80 injection can cause serious allergic reactions, and CBZ itself has strong toxicity, adverse reactions, and poor tumor selectivity, which greatly limits its clinical applications. Therefore, the CBZ-loaded bovine serum albumin nanoparticles (CBZ-BSA-Gd-NPs) were developed to overcome the allergenic response of Tween 80 and realize the integration of diagnosis and treatment.Methods: CBZ-BSA-Gd-NPs were prepared by the biomineralization method. The characterization, magnetic resonance imaging (MRI), safety, and antitumor activity of the nanoparticles were evaluated in vitro and in vivo.Results: The prepared nanoparticles were uniform in size (166 nm), with good MRI performance and stability over 24 h. Compared with CBZ-Tween 80 injection, CBZ-BSA-Gd-NPs showed much lower hemolysis, similar tumor inhibition, and enhanced cellular uptake in vitro. The pharmacokinetic behavior of CBZ-BSA-Gd-NPs in rats showed that the retention time of the nanoparticles was prolonged, the clearance rate decreased, and the area under the drug-time curve increased. The distribution of CBZ-BSA-Gd-NPs in nude mice was characterized by UPLC-MS/MS and MRI, and the results showed that CBZ-BSA-Gd-NPs could effectively target tumor tissues with reduced distribution in the heart, liver, spleen, lungs, and kidneys compared with CBZ-Tween 80, which indicated that CBZ-BSA-Gd-NPs not only had a passive targeting effect on tumor tissue but also achieved the integration of diagnosis and treatment. In vivo, CBZ-BSA-Gd-NPs showed improved tumor inhibitory effect with a safer profile.Conclusion: In summary, CBZ-BSA-Gd-NPs can serve as an effective therapeutic drug carrier to deliver CBZ into prostate cancer, and realize the integration of diagnosis and therapy.Keywords: cabazitaxel, bovine serum albumin, nanoparticles, prostate cancer, magnetic resonance imaging, gadolinium

Piotr Orlowski,1 Magdalena Zmigrodzka,2 Emilia Tomaszewska,3 Katarzyna Ranoszek-Soliwoda,3 Beata Pajak,4 Anna Slonska,5 Joanna Cymerys,5 Grzegorz Celichowski,3 Jaroslaw Grobelny,3 Malgorzata Krzyzowska1 1Laboratory of Nanobiology and Biomaterials, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; 2Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), Warsaw, Poland; 3Department of Materials Technology and Chemistry, Faculty of Chemistry, University of Lodz, Lodz, Poland; 4Laboratory of Genetics and Molecular Biology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; 5Division of Microbiology, Department of Preclinical Sciences, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw 02-786, PolandCorrespondence: Malgorzata Krzyzowska Email krzyzowskam@yahoo.comBackground: Polyphenols possess antioxidant, anti-inflammatory and antimicrobial properties and have been used in the treatment of skin wounds and burns. We previously showed that tannic acid-modified AgNPs sized > 26 nm promote wound healing, while tannic acid-modified AgNPs sized 13 nm can elicit strong local inflammatory response. In this study, we tested bimetallic Au@AgNPs sized 30 nm modified with selected flavonoid and non-flavonoid compounds for wound healing applications.Methods: Bimetallic Au@AgNPs were obtained by growing an Ag layer on AuNPs and further modified with selected polyphenols. After toxicity tests and in vitro scratch assay in HaCaT cells, modified lymph node assay as well as the mouse splint wound model were further used to access the wound healing potential of selected non-toxic modifications.Results: Tannic acid, gallic acid, polydatin, resveratrol, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and procyanidin B2 used to modify Au@AgNPs exhibited good toxicological profiles in HaCaT cells. Au@AgNPs modified with 15 μM tannic acid, 200 μM resveratrol, 200 μM epicatechin gallate, 1000 μM gallic acid and 200 μM procyanidin B2 induced wound healing in vivo and did not lead to the local irritation or inflammation. Tannic acid-modified Au@AgNPs induced epithelial-to-mesenchymal transition (EMT) – like re-epithelialization, while other polyphenol modifications of Au@AgNPs acted through proliferation and wound closure.Conclusion: Bimetallic Au@AgNPs can be used as a basis for modification with selected polyphenols for topical uses. In addition, we have demonstrated that particular polyphenols used to modify bimetallic nanoparticles may show different effects upon different stages of wound healing.Keywords: polyphenols, bimetallic nanoparticles, wound healing, mouse model

Weizong Weng,1,2,* Xiaoqun Li,1,* Wei Nie,3 Haoyuan Liu,2 Shanshan Liu,2 Jianming Huang,2 Qirong Zhou,1 Jia He,1 Jiacan Su,1 Zhifeng Dong,4 Dongliang Wang5 1Department of Orthopeadics, Changhai Hospital affiliated to the Second Military Medical University, Shanghai 200433, People's Republic of China; 2Orthopaedics Department, Chenggong Hospital Affilaited to Xiamen University, Xiamen 361000, People's Republic of China; 3College of Chemistry, Chemical Engineering and Biotechnology, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China; 4Department of Cardiology, Shanghai Sixth Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200233, People's Republic of China; 5Orthopeadics Department, Xinhua Hospital Affiliated to the Shanghai Jiaotong University, Shanghai 200433, People's Republic of China*These authors contributed equally to this workCorrespondence: Dongliang Wang; Weizong Weng Email wangdongliang@xinhuanmed.com.cn; drwengweizong@163.comBackground: Bactericidal capacity, durable inhibition of biofilm formation, and a three-dimensional (3D) porous structure are the emphases of infected bone defect (IBD) treatment via local scaffold implantation strategy.Purpose: In this study, silver nanoparticle (AgNP)-loaded nano-hydroxyapatite (nHA)@ reduced graphene oxide (RGO) 3D scaffolds (AHRG scaffolds) were designed to alleviate bone infection, inhibit biofilm formation, and promote bone repair through the synergistic effects of AgNPs, RGO, and nHA.Materials and Methods: AHRGs were prepared using a one-step preparation method, to create a 3D porous scaffold to facilitate a uniform distribution of AgNPs and nHA. Methicillin-resistant Staphylococcus aureus (MRSA) was used as a model-resistant bacterium, and the effects of different silver loadings on the antimicrobial activity and cytocompatibility of materials were evaluated. Finally, a rabbit IBD model was used to evaluate the therapeutic effect of the AHRG scaffold in vivo.Results: The results showed successful synthesis of the AHRG scaffold. The ideal 3D porous structure was verified using scanning electron microscopy and transmission electron microscopy, and X-ray photoelectron spectroscopy and selected area electron diffraction measurements revealed uniform distributions of AgNP and nHA. In vitro antibacterial and cytocompatibility indicated that the 4% AHRG scaffolds possessed the most favorable balance of bactericidal properties and cytocompatibility. In vivo evaluation of the IBD model showed promising treatment efficacy of AHRG scaffolds.Conclusion: The as-fabricated AHRG scaffolds effectively eliminated infection and inhibited biofilm formation. IBD repair was facilitated by the bactericidal properties and 3D porous structure of the AHRG scaffold, suggesting its potential in the treatment of IBDs.Keywords: biofilm, graphene oxide, hydroxyapatite, infected bone defect, scaffold, silver nanoparticles, three-dimensional

Yujie Li,1,2 Fengxiang Li,2 Lincong Zhang,2 Chi Zhang,2 Hui Peng,2 Feng Lan,3 Shuangqing Peng,2 Chao Liu,1,2 Jiabin Guo1,2 1Graduate School, Academy of Military Medical Sciences, Beijing, People's Republic of China; 2Department of Operational Medical Protection, PLA Center for Disease Control and Prevention, Beijing, People's Republic of China; 3Beijing Key Laboratory for Cardiovascular Precision Medicines, Anzhen Hospital, Capital Medical University, Beijing, People's Republic of ChinaCorrespondence: Chao Liu Tel +86-10-66948389Email liuchao9588@aliyun.comJiabin Guo Tel +86-10-66948463Email gjb321@163.comBackground: Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in a variety of fields such as industrial, pharmaceutical, and household applications. Increasing evidence suggests that ZnO NPs could elicit unignorable harmful effect to the cardiovascular system, but the potential deleterious effects to human cardiomyocytes remain to be elucidated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been increasingly used as a promising in vitro model of cardiomyocyte in various fields such as drug cardiac safety evaluation. Herein, the present study was designed to elucidate the cardiac adverse effects of ZnO NPs and explore the possible underlying mechanism using hiPSC-CMs.Methods: ZnO NPs were characterized by transmission electron microscopy and dynamic light scattering. The cytotoxicity induced by ZnO NPs in hiPSC-CMs was evaluated by determination of cell viability and lactate dehydrogenase release. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by high-content analysis (HCA). Mitochondrial biogenesis was assayed by detection of mtDNA copy number and PGC-1α pathway. Moreover, microelectrode array techniques were used to investigate cardiac electrophysiological alterations.Results: We demonstrated that ZnO NPs concentration- and time-dependently elicited cytotoxicity in hiPSC-CMs. The results from HCA revealed that ZnO NPs exposure at low-cytotoxic concentrations significantly promoted ROS generation and induced mitochondrial dysfunction. We further demonstrated that ZnO NPs could impair mitochondrial biogenesis and inhibit PGC-1α pathway. In addition, ZnO NPs at insignificantly cytotoxic concentrations were found to trigger cardiac electrophysiological alterations as evidenced by decreases of beat rate and spike amplitude.Conclusion: Our findings unveiled the potential harmful effects of ZnO NPs to human cardiomyocytes that involve mitochondrial biogenesis and the PGC-1α pathway that could affect cardiac electrophysiological function.Keywords: Zinc oxide nanoparticles, ZnO NPs, human induced pluripotent stem cells-derived cardiomyocytes, hiPSC-CMs, cardiac dysfunction, mitochondrial biogenesis, PGC-1α

Indonesia's border region to Phillippines, especially to the Sangihe Islands which borders to southern, is mostly a less developed area. To accelerate development of this border region, Indonesia and the Philippines need to exercise a strategy which optimize social connectivity which has been existed since centuries by the Indonesian Sangihe people known as Sangir-Philippines ("Sapi") or the Philippines-Sangir ("Pisang"). Although they are sovereign states now with their sovereign territorial rights, these facts do not prevent these peoples to continue their traditional cross border for the purpose of social, culture and economic activities. This paper examines how their social connectivity could be utilized to develop border area between Indonesia and the Philippine. By using qualitative methods, the data for this paper is collected from interviews, focus group discussions, field research and literature reviews.This paper concludes that social connectivity among Sapi/Pisang people on the Indonesian and the Philippines respective side raises some challenges such as problems of stateless people, illegal cross-border activities, and terrorism-related activities. However, this paper also found out some positive impacts from their social connectivities, such as the establishment of traditional cross-border cooperation and trade, the opening of the Davao-Bitung ferry line, and cooperation between regional governments. As a step forward, this research emphasizes the importance of strong political will and active participation from both countries in utilizing social connectivity to build a shared border region.Keywords: "Sapi", "Pisang", Border, Social Connectivity, Development, Indonesia, Philippine AbstrakKawasan Perbatasan Indonesia di Kepulauan Sangihe yang berbatasan dengan Filipina bagian selatan, tergolong sebagai daerah tertinggal. Untuk mempercepat pembangunan kawasan tersebut, Indonesia dan Filipina dapat melaksanakan strategi yang memanfaatkan konektivitas sosial yang sudah dibangun oleh masyarakat perbatasan yang dikenal dengan istilah Sangir-Philipina (Sapi) atau Philipina-Sangir (Pisang). Berdirinya Indonesia dan Filipina sebagai dua negara yang berdaulat sejak berakhirnya Perang Dunia II ternyata tidak menghentikan orang Sapi/Pisang untuk melakukan kegiatan lintas batas tradisional untuk tujuan sosial, budaya, dan ekonomi. Tulisan ini menganalisis bagaimana dampak negatif dan dampak positif dari konektivitas sosial di atas dalam membangun kawasan perbatasan Indonesia-Filipina. Dengan menggunakan pendekatan kualitatif, pengumpulan data dilakukan melalui wawancara, diskusi kelompok terpimpin, penelitian lapangan dan studi pustaka. Tulisan ini menyimpulkan bahwa konektivitas sosial antar orang-orang Sapi/Pisang di sisi Indonesia dan di sisi Filipina menimbulkan masalah berupa orang-orang tanpa kewarganegaraan, kegiatan lintas batas ilegal, dan aktivitas terkait terorisme. Namun demikian, Tulisan ini juga menemukan dampak positif dari konektivitas sosial di atas berupa terjalinnya kerja sama lintas batas tradisional dan perdagangan, pembukaan jalur kapal feri Davao-Bitung, dan kerja sama antar pemerintah daerah. Sebagai langkah ke depan, penelitian ini menekankan pentingnya kehendak politik yang kuat dan partisipasi aktif dari kedua negara dalam memanfaatkan konektivitas sosial untuk membangun kawasan perbatasan bersama.