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Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.
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Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.
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Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
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Cancer stem cells (CSCs) are a subpopulation of cancer cells with functions similar to those of normal stem cells. Although few in number, they are capable of self-renewal, unlimited proliferation, and multi-directional differentiation potential. In addition, CSCs have the ability to escape immune surveillance. Thus, they play an important role in the occurrence and development of tumors, and they are closely related to tumor invasion, metastasis, drug resistance, and recurrence after treatment. Therefore, specific targeting of CSCs may improve the efficiency of cancer therapy. A series of corresponding promising therapeutic strategies based on CSC targeting, such as the targeting of CSC niche, CSC signaling pathways, and CSC mitochondria, are currently under development. Given the rapid progression in this field and nanotechnology, drug delivery systems (DDSs) for CSC targeting are increasingly being developed. In this review, we summarize the advances in CSC-targeted DDSs. Furthermore, we highlight the latest developmental trends through the main line of CSC occurrence and development process; some considerations about the rationale, advantages, and limitations of different DDSs for CSC-targeted therapies were discussed.
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Exosomes are membranous vesicles that are actively secreted by cells. They can be isolated from various cell culture media and animal body fluids. Exosomes are mainly composed of lipids, proteins and nucleic acids. They have small molecular structure and high biocompatibility with size of 40-100 nm. In addition, exosomes are natural endogenous nanocarriers that can transport lipids, proteins, DNA and RNA. Studies have shown that exosomes play an important role in long-distance communication between cells, in physiological and pathological processes. This article introduces the composition and physiological functions of exosomes, and summarizes the relevant content of exosomes as drug delivery vehicles. The applications of exosomes in central nervous system diseases, especially brain diseases and tumors are summarized.
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In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability (less than 1%-2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.
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Objective To analyze the characteristics ofgastroesophageal reflux disease (GERD) under general gastroscope.Methods The detection rates of GERD related abnormalities such as esophagitis,Barrett esophagus and hiatal hernia under the first gastroscopy of the adult GERD patients from January 2013 to January 2017 in our center and the statistical relationship between the abnormal findings were analyzed retrospectively.Results A total of 4086 GERD patients,2004 males and 2082 females,were included in this study,and the age was 18-89(50.4 ± 13.3) years old.The detection rate of non erosive GERD was 78.7％,esophagitis 21.3％;non Barrett esophagus 87.7％,suspected Barrett esophagus 8.3％,Barrett esophagus 3.9％;generally normal cardia 61.4％,short segment hiatus hernia 20.4％,and long segment hiatal hernia 18.2％.The detection rates of esophagitis showed statistically significant differences (P＜0.001) between the three groups of generally normal cardia,short segment hiatal hernia and long segment hiatal hernia;The detection rate of Barrett esophagus was significantly higher in long segment hiatal hernia group than in generally normal cardia group and short segment hiatal hernia group (P＜0.001,P=0.012),but the difference between the later two groups was not statistically significant (P＞0.013).Comparing the three age groups of 18-39,40-59 and ≥60 years old,the detection rate of hiatal hernia was significantly higher in the group of≥60 years old than in the 18-39 and 40-59 years old groups (P=0.007),while there was no significant difference (P＞0.013) between the 18-39 and 40-59 years old groups.The detection rate of esophagitis was significantly higher in ≥60 years old group than in 18-39 and 40-59 years old groups (P=0.004,P=0.008),while no significant statistically difference (P＞0.013) was found between the later two groups.Conclusions Gastroscopy can be used as a basic examination means for GERD;short segment hiatal hernia can be regarded as an early form of hiatal hernia,and is of important reference value for the diagnosis and treatment of GERD;more serious hiatal hernia and esophagitis could be found in elderly GERD patients.
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Anti-tumor antibiotics exhibit great application potential in the anti-tumor therapy. Some drugs have become the first-line medication clinically. However, there are always various problems associated with anti-tumor antibiotics, such as poor solubility and instability as well as severe systemic side effects. It is important to choose suitable delivery carriers for a reasonable delivery system for a good targeting ability, enhanced anti-tumor efficacy and reduced adverse effects of the anti-tumor antibiotics, especially in the smart delivery systems. This review summarizes the carriers and the advances in the delivery systems of anti-tumor antibiotics, including anti-tumor antibiotic drugs currently on the market, in the clinical research stage and in the basic research stage.
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Objective To evaluated the safety and feasibility of excimer laser atherectomy (ELA) combined with drug-eluting balloon angioplasty in treating chronic ischemia of lower limbs.Methods ELA combined with paclitaxel-eluting balloon angioplasty was adopted to treat chronic ischemia of lower limbs caused by arteriosclerosis occlusive disease of lower extremity in three patients.All three patients had arteriosclerosis occlusive disease of superficial femoral artery;in two of them the disease was primary occlusive lesion and in another patient the disease was in-stent re-occlusion lesion after sten implantation.Results After the treatment,the blood flow in the diseased arteries was unobstructed,the blood supply of the lower limbs was obviously improved.No procedure-related complications occurred.Two weeks after the treatment,no recurrence of ischemic symptoms was observed,the blood flow in superficial femoral artery kept unobstructed.The patients recovered smoothly.Conclusion For the treatment of chronic ischemia of lower limbs,which are caused by the primary arteriosclerosis occlusive disease of lower extremity or by the in-stent re-occlusion lesion after sten implantation,ELA combined with paclitaxel-eluting balloon angioplasty is clinically safe and feasible,although its long-term effect needs to be clarified with more studies.
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Cell membrane serves as the natural barrier. Cell-penetrating peptides (CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticu-late pharmaceutical carriers (e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demon-strated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.
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Central nervous system(CNS)diseases are serious threats to human health. Blood-brain barrier(BBB)plays an im?portant role in protecting the CNS. However,it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article,we introduce the phys?iological structure and functions of BBB,and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.
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Objective To discuss the key points of endovascular therapy for complex subclavian artery occlusive diseases. Methods During the period from January 2012 to December 2013, a total of 92 patients with complex subclavian artery occlusive disease were admitted to Xuanwu Hospital of Capital Medical University, Beijing, China. The clinical data were retrospectively analyzed. The features of the lesions, the success rate of endovascular therapy, the use of combined approaches, the relief of symptoms after treatment, etc. were evaluated. Results The complex subclavian artery occlusive diseases could be divided into three types. Type Ⅰ: long segment of the left subclavian artery was occluded; type Ⅱ: ostial stenosis or occlusion of the right subclavian artery; and type Ⅲ: subclavian artery stenosis or occlusion was associated with the ostial disorder of the vertebral artery, or the opening of vertebral artery was affected by the subclavian artery stenosis or occlusion. The technical success rate was 82.6%. Combination use of femoral artery and brachial artery approach was employed in 27.2% of patients, which had improved the technical success rate. After the treatment the symptom improvement rate was 81.6%. Conclusion Upper limb artery approach can improve the re-canalization rate of left subclavian artery with long segment occlusion, and can ensure the accurate positioning of stent at the site of right subclavian artery opening. During the procedure of endovascular intervention for subclavian artery occlusion disease, attention should be paid to the protection of the vertebral artery.
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Traditional treatments for malignant tumor are far from meeting the clinical demands.Recently,research on anti-tumor targeted drugs has made a significant breakthrough,which brings new hope for the treatment of malignant tumor.Anti-tumor targe-ted drugs can specifically target malignant tumor and directly in-hibit the growth of tumor cells,showing no toxicity to the normal tissues and organs.Herein we reviewed the research progress of small molecular targeted drugs and antibody targeting new drugs.
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The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.
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This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
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Objective This study aimed to optimize the preparation condition of DNA-chitosan nanoparticles with high transfec-tion efficency through a central composition design .Methods The DNA-chitosan nanoparticles were prepared by complex coacervation between pEGFP and chitosan .We selected the concentrations of chitosan and plasmid as two experimental factors , and a central compos-ite design with two factors and five levels was used to optimize the preparation condition of DNA-chitosan nanoparticles for high transfec-tion efficency .The concentrations of chitosan and plasmid were selected as the independent variables , respectively .The dependent varia-bles included average particle size and transfection efficiency .The morphology of DNA-chitosan nanoparticles was observed using a trans-mission electron microscope .The size and zeta potential of nanoparticles were measured by dynamic light scattering ( DLS) and electro-phoretic light scattering ( ELS ) , respectively .The stability of plasmids in the process of nanoparticles preparation was investigated through the agrose gel electrophoresis .The expression of plasmids delivered by nanoparticles was observed under an inverted fluorescence microscope .The transfection efficiency of DNA-chitosan nanoparticles was assayed by flow cytometry .Results The preparation condition of DNA-chitosan nanoparticles with high transfection efficency was optimized successfully .Under the optimum preparative conditions , the DNA-chitosan nanoparticles were almost spherical .The average size of nanoparticles was 217.6nm, and distributed in a narrow range with a polydispersity index of 0.241.The zeta potential was +22.4 mV, which suggested that a den-sity of positive charge exist onto the surface of nanoparticles and consequently enhanced the stability of nanoparticles suspension .The results of gel electrophoresis showed that plasmids were not destroyed in the process of nanoparticles preparation .The cell transfection of nanoparticles was very highly efficient .The nanoparticles could effectively deliver the pEGFP plasmids into cells to express the green fluorescent protein at a high level.Conclusion The established mathematic models have the good predictive function .Under the optimum preparative condi-tions, the DNA-chitosan nanoparticles have the high potential of cell transfection .
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This study primarily focused on the systematic assessment of both in vitro and in vivo anti-tumor effects of docetaxel-loaded polyethylene glycol (PEG)2000-polycaprolactone (PCL)2600 micelles on hormone-refractory prostate cancer (HRPC). By using solvent evaporation method, PEG-PCL was chosen to prepare doxetaxel (DTX)-loaded mPEG-PCL micelles (DTX-PMs), with the purpose of eliminating side effects of the commercial formulation (Tween 80) and prolonging the blood circulation time. The prepared DTX-PMs had an average particle size of 25.19±2.36 nm, a zeta potential of 0.64±0.15 mV, a polydispersity index of 0.56±0.03, a drug loading of (8.72±1.05)%, and an encapsulation efficiency of (98.1±8.4)%. In vitro cytotoxicity studies indicated that DTX-PMs could effectively kill LNCap-C4-2B cells and show a dose- and time-dependent efficacy. The hemolysis test showed that DTX-PMs had less hemocytolysis than the commercial product of Duopafei®. A sustained in vitro release behavior and prolonged circulation time in blood vessels were observed in the DTX-PMs. Furthermore, when compared with Duopafei®, the DTX-PMs dramatically reduced the prostate specific antigen (PSA) level and tumor growth of prostate tumor-bearing nude mice in vivo. In conclusion, the DTX-PMs can lower systemic side effects, improve anti-tumor activity with prolonged blood circulation time, and will bring an alternative to patients with HRPC.
Subject(s)
Animals , Humans , Male , Mice , Rats , Antineoplastic Agents , Pharmacokinetics , Pharmacology , Area Under Curve , Cell Line, Tumor , Cell Survival , Dose-Response Relationship, Drug , Guinea Pigs , Hemolysis , Mice, Nude , Micelles , Particle Size , Polyesters , Chemistry , Polyethylene Glycols , Chemistry , Prostatic Neoplasms , Drug Therapy , Pathology , Rats, Sprague-Dawley , Taxoids , Chemistry , Pharmacokinetics , Pharmacology , Treatment Outcome , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
Objective To establish a simple and efficient method for developing a keloid model in nude mice with human keloid-derived fibroblasts.Methods Twenty-seven female BALB/c nude mice were randomly divided into five groups with 5,5,5,8 and 4 mice in group A,B,C,D and E respectively.The mice in group A,B and C were inoculated with 0.1 ml of suspension containing human keloid-derived fibroblasts at concentrations of 1.0 × 104,3.0 × 104 and 5.0 × 104 per microliter Matrigel,respectively,at the right axillary fossa.The tumors that formed in one mouse in group C were taken out,and cut into several parts measuring 5 mm × 5 mm × 5 mm in size,which were then subcutaneously transplanted into the right axillary fossa of mice in group D.The mice in group E were subcutaneously injected with 100 μl of Matrigel and served as the control group.The formation of tumor in mice was observed by naked eyes,and the size of tumors was measured until day 30 after tumor formation in group A,B and C as well as after tumor transplantation in group D.Mice were sacrificed on day 30 after tumor formation,and histopathologic examination was performed to analyze histological features of transplanted tumors and pathological changes in visceral organs such as heart,liver,spleen,lung and kidney.Results The tumor formation rate was consistently 100％ in group A,B and C,and the time required for tumor formation was (90.20 ± 3.96),(61.00 ± 2.92) and (39.60 ± 3.20) days in group A,B and C respectively.There was a significant difference in tumor volume on the 30th day after tumor formation between group A,B and C ((288.34 ± 25.29) vs.(1 370.63 ± 105.24) vs.(1 940.98 ± 184.37) mm3,F =138.74,P ＜ 0.05).The size of implanted tumor mass in group D firstly increased,then gradually decreased,but began to continuously increase since the 14~ day,and tumor finally formed in 7 out of 8 mice.There was no evidence of tumor formation in group E.Histopathologic examination showed uniform histological manifestations,which were similar to those of human scar,in tumor tissues from mice in group A,B,C and D.Neither pathological changes nor metastases were observed in visceral organs of these mice.Conclusion Keloid-bearing nude mouse model can be established by subcutaneous inoculation with human keloidderived fibroblasts,or by subcutaneous transplantation of tumor masses of a certain size that have formed in nude mice.
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<p><b>BACKGROUND</b>Totally laparoscopic aortic surgery is still in its infancy in China. One of the factors preventing adoption of this technique is its steep learning curve. The objective of this study was to evaluate the feasibility and safety of laparoscopic surgery for aortoiliac occlusive disease (AIOD).</p><p><b>METHODS</b>From November 2008 to November 2012, 12 patients were treated for severe AIOD with a totally laparoscopic bypass surgery at our university hospital. The demographic data, operative data, postoperative recovery data, morbidity and mortality were analyzed and compared with those of conventional open approach.</p><p><b>RESULTS</b>Twelve totally laparoscopic aortic surgery procedures, including two iliofemoral bypasses (IFB), three unilateral aortofemoral bypasses (UAFB), and seven aortobifemoral bypasses (ABFB), were performed. Conversion to open procedures was required in three patients. The mean operation time was 518 (range, 325-840) minutes, mean blood loss was 962 (range, 400-2500) ml, and mean aortic anastomosis time was 75 (range, 40-150) minutes. Compared with conventional open approach for aortofemoral bypasses performed concomitantly during this period, laparoscopic patients required fewer narcotics and a shorter in-hospital stay and earlier recovery. Postoperative complications developed in four patients, including a single patient with transient left hydronephrosis, ischemic colonic fistula and pneumonia, residual aortic stenosis proximal to the anastomotic site, and asymptomatic partial left renal infarction. All patients recovered and were discharged on postoperative Days 7-14 except one patient that died of respiratory failure on Day 46. All grafts were patent with follow-up imaging performed by Duplex examination, with a mean follow-up time of 10.7 (range, 2-61) months.</p><p><b>CONCLUSION</b>Totally laparoscopic bypass surgery is a feasible and safe procedure for AIOD, but attention needs to be paid to improve laparoscopic skills of vascular surgery in order to minimize morbidity during the learning curve of this advanced procedure.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Aortic Diseases , General Surgery , Arterial Occlusive Diseases , General Surgery , Iliac Artery , General Surgery , Laparoscopy , Methods , Postoperative ComplicationsABSTRACT
<p><b>BACKGROUND</b>Percutaneous transluminal renal angioplasty with stent is an effective procedure for atherosclerotic renal artery stenosis. However, the decision to perform this procedure has recently raised considerable debate. The aim of this study was to assess the effects of percutaneous transluminal renal angioplasty with stent in atherosclerotic renal artery stenosis patients, especially as it relates to blood pressure control and renal function improvement.</p><p><b>METHODS</b>A retrospective analysis was made of the clinical data from 125 atherosclerotic renal artery stenosis patients who underwent percutaneous transluminal renal angioplasty from July 2004 to June 2008 in the Department of Vascular Surgery of Beijing Chaoyang Hospital. We compared blood pressure, number of oral antihypertensive medications, and renal function changes pre and post-procedure at 24 months follow-up.</p><p><b>RESULTS</b>A total of 125 atherosclerotic renal artery stenosis patients underwent percutaneous transluminal renal angioplasty and 143 stents were placed. At 24 months follow-up, both systolic and diastolic blood pressure and the number of oral antihypertensive medications were significantly reduced (P < 0.05). Overall, the estimated glomerular filtration rate did not change significantly (P > 0.05); however, a significant increase in estimated glomerular filtration rate was observed in the subgroup of patients with a lower baseline estimated glomerular filtration rate and in the subgroup of patients with bilateral renal artery stenosis (P < 0.05).</p><p><b>CONCLUSION</b>Percutaneous transluminal renal angioplasty is a safe procedure for atherosclerotic renal artery stenosis patients, providing a significant improvement in blood pressure control and reduction in the number of oral antihypertensive medications.</p>