Drug-eluting polymer implants in cancer therapy

Background: Drug-eluting polymer implants present a compelling parenteral route of administration for cancer chemotherapy. With potential for minimally invasive, image-guided placement and highly localized drug release, these delivery systems are playing an increasingly important role in cancer management. This is particularly true as the use of labile proteins and other bioactive molecules is likely to increase in the upcoming years. Objective: In this review, we present the current trends in the application of Pre-formed and in situ-forming systems as drug-eluting implants for cancer chemotherapy. Methods: We outline the clinically available options as well as up-and-coming technologies and their advantages and challenges. We also describe ongoing related innovations with image-guided drug delivery, mathematical modeling of implanted delivery systems and implanted drug delivery in combination with other therapies. Results/conclusion: Whether used alone or combined with other minimally invasive procedures, drug-eluting polymeric implants will play a significant role in the future of cancer management.     

Drug-eluting polymer implants in cancer therapy

BACKGROUND: Drug-eluting polymer implants present a compelling parenteral route of administration for cancer chemotherapy. With potential for minimally invasive, image-guided placement and highly localized drug release, these delivery systems are playing an increasingly important role in cancer management. This is particularly true as the use of labile proteins and other bioactive molecules is likely to increase in the upcoming years. Objective: In this review, we present the current trends in the application of Pre-formed and in situ-forming systems as drug-eluting implants for cancer chemotherapy. METHODS: We outline the clinically available options as well as up-and-coming technologies and their advantages and challenges. We also describe ongoing related innovations with image-guided drug delivery, mathematical modeling of implanted delivery systems and implanted drug delivery in combination with other therapies. RESULTS/CONCLUSION: Whether used alone or combined with other minimally invasive procedures, drug-eluting polymeric implants will play a significant role in the future of cancer management.     

Drug-eluting stents for acute myocardial infarction

This is a review of the literature comparing the efficacy and safety of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with acute myocardial infarction (MI). The present article reviews whether DES are beneficial in the setting of primary percutaneous coronary intervention (PCI), and this has been the subject of many recent publications and debate among clinicians. To the best of our knowledge there are limited registries and randomized trials about DES for acute MI in the English literature. Bare-metal stents have a higher incidence of instent restenosis whereas DES might have a slightly higher late thrombosis risk. With the current data DES might still have an advantage over BMS in the treatment of ST-segment elevation MI (STEMI) patients with the vastly improved target vessel revascularization rates. Despite the lack of well-designed head-to-head long-term prospective clinical trials, DES may not be effective in patients who are on short-term dual antiplatelet therapy owing to an increased risk of late stent thrombosis. In conclusion, DES use in STEMI patients continuing long-term dual antiplatelet therapy is safe and effective.     

Drug-eluting stents: beyond the hyperbole

Drug-eluting stents (DES) promised to reduce the clinical and economic cost of failed bare metal stents (BMS) by locally delivering a therapeutic agent to the injured artery, reducing or eliminating the development of neointimal hyperplasia and reducing the need for repeat interventions to re-open the obstructed artery. Data from initial large-scale, comparable, U.S. pivotal trials of the first two DES to reach the American market, CYPHER from J&J using the drug rapamycin (sirolimus) and TAXUS from Boston Scientific using the drug paclitaxel (taxol), seemed to warrant the enthusiasm. By reducing the failure rate of BMS by about 4-fold, DES have changed clinical practice, reduced the rate of coronary bypass surgery, had a significant economic impact, and triggered extensive research in the areas of stent design, restenosis biology, polymeric drug-delivery and local pharmacology and toxicology.     

Drug-eluting stents: present and future

In-stent restenosis (ISR) caused by neointimal hyperplasia is the major drawback after percutaneous coronary intervention (PCI) for obstructive coronary disease, occurring in up to 40% of lesions. Recently, one of the most intriguing new therapies developed is drug-eluting stents (DES) that target the central phenomenon of cellular proliferation that causes ISR. The benefits of stent-based drug delivery include maximizing the local tissue levels of therapeutic agents while minimizing systemic toxicity. Numerous DES using different thin-film polymeric drug carrier have been developed and tested, those eluting either antimitotic or antimicrotublar agents such as sirolimus and paclitaxel have been shown effective in clinical trials. Two DES, the J&J Cypher (sirolimus-eluting) and the Boston Scientific Taxus (paclitaxel-eluting) stents, are commercially available in the U.S. after a number of randomized trials demonstrated reductions in late lumen loss, binary restenosis rate, and need for repeat revascularization compared with bare-metal stents (BMS). Because ISR is multifactorial, ideal agents for DES should inhibit thrombus formation, inflammation and cellular proliferation as well as enhance re-endothelialization. The next generation of DES currently undergoing preclinical studies includes new technology, new stent designs and materials, biological polymers, bioabsorbable stents coated with new drugs including stent based gene, as well as cell delivery. The current paper will review and discuss the current and future status of DES.     

Treatment options for diabetic foot osteomyelitis

Introduction: Diabetic foot osteomyelitis therapeutical options are based on antibiotic therapy and surgical resection of the infected bone(s). Surgical and medical approaches of patients suffering from a diabetic foot osteomyelitis do not oppose but are complementary and need to be discussed as a tailored manner.

Areas covered: The aim of the present article is to discuss data issued from the most recent guidelines of the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot on the management of the diabetic foot infection and from a search in the current literature using the terms diabetic foot osteomyelitis and treatment/therapy/therapeutical in both PubMed and Medline, restricted to the last five years.

Expert opinion: Surgical removal of the entire infected bone(s) has been considered in the past as the standard treatment but medical approach of these patients has now proven efficacy in selected situations. The current emergence of bacteria, especially among Gram negative rods, resistant to almost all the available antibiotics gradually augments the complexity of the management of these patients and is likely to decrease the place of the medical approach and to worsen the outcome of these infections in the next future.     

Drug-eluting stents: factors governing local pharmacokinetics

Stent-based drug delivery system is a revolutionary approach to mitigate the negative affects of balloon angioplasty, improve immune responsiveness and prevent hyperplastic growth of smooth muscle in the restenotic state. Its success is therefore empirically associated with effective delivery of potent therapeutics to the target site at a therapeutic concentration, for a sufficient time, and in a biologically active form. However, local delivery with drug-eluting stents imparts large dynamic concentration gradients across tissues that can be difficult to identify, characterize and control. This review explores the factors such as physiological transport forces, drug physicochemical properties, local biological tissue properties and stent design that governs the local pharmacokinetics within the arterial wall by drug-eluting stent. Rational design and optimization of drug-eluting stents for local delivery thus requires a careful consideration of all these factors.     

Drug-eluting stents: a multidisciplinary success story

Coronary stenting is the most common form of interventional treatment for symptomatic coronary artery disease. In-stent restenosis following bare metal stent (BMS) placement is the most common cause of procedural failure and occurs as a result of vessel wall trauma secondary to balloon angioplasty and stent deployment that results in an overly aggressive healing response (neointimal hyperplasia) that overgrows the stent lumen and causes vascular narrowing. Drug-eluting stents (DES) are specialized vascular stents capable of delivering drugs to the arterial wall in a controlled manner such that neointimal hyperplasia is reduced or prevented, luminal patency is preserved, coronary blood flow is maintained and the patient is spared a repeat procedure to re-open the vessel. The objectives of the review are to provide an overview of the major contributions that a broad range of disciplines have made to the design and development of drug-eluting stents and to summarize future directions of these fields of research. Engineers and biomaterials scientists have explored relationships between stent design and stent performance and work continues to optimize stent design and biocompatibility of stent biomaterials. Pharmaceutical scientists are continually expanding the range of candidate drugs for pharmacological intervention, and improving the technology using novel coatings to modulate drug release. Clinical scientists are investigating issues such as long-term safety and efficacy, new applications of drug-eluting stents and optimal deployment techniques.     

种植体表面处理相关研究

目的为选择可获得最佳骨结合效果的表面处理方式及条件。方法以TA1经机械加工后的螺旋柱状植体为标本(直径3.8mm长度10mm),分为机械加工组、喷砂处理组、喷砂酸蚀处理组,进行电镜观察以确定其形态。以扫描电镜,EDS-X射线能谱仪分析测试其表面成分,以XPS-X射线光电子能谱分析,测量其表面附着离子。结果以喷砂50%、60%酸蚀组各项指标提示其为最适宜骨结合条件。结论喷砂、酸蚀处理的植体表面的结果支持目前常用的种植体。清洁过程不足,导致表面离子改变,提示植体处理过程中环境的重要性。     

创伤性胫骨骨髓炎应用抗生素骨水泥治疗的临床疗效观察

目的 探讨创伤性胫骨骨髓炎应用抗生素骨水泥治疗的临床疗效.方法 收集2015年4月至2016年4月入院的100例创伤性胫骨骨髓炎患者,随机分为两组,对照组患者给予抗生素局部灌注,实验组患者则给予抗生素骨水泥治疗,比较两组患者疾病相关临床参数、总体治疗效果、抗感染指标、疼痛与功能水平.结果 实验组患者细菌培养转阴时间为(14.06±2.11)d、创面愈合时间为(26.33±4.75)d、换药次数为(5.71±0.96)次与住院时间为(29.30 ±4.14)d,均显著低于对照组[(17.13±2.32)d,(30.70±4.09)d,(7.66±1.12)次,(33.74±4.51)dl术后4周WBC计数为(8.71±0.68)×109,Hs-CRP水平为(2.03±0.54)mg/L,组间比较均显著低于对照组[(9.77±0.80)×109,(3.27±0.63)mg/L];末次随访VAS评分为(1.54±0.24)分,组间比较显著低于对照组的(1.94±0.31)分,HHS评分为(89.81±7.48)分与Baird-Jackson评分为(84.54±6.92)分,组间比较均显著高于对照组[(72.35±7.50)分,(71.09±6.74)分],差异均有显著统计学意义(均P＜ 0.01);创面感染控制率(100％)与总有效率(100％)明显高于对照组(90％,88％),复发率(6％)明显低于对照组(12％),差异有统计学意义(P＜0.05).结论 创伤性胫骨骨髓炎应用抗生素骨水泥治疗的临床疗效显著,具有借鉴意义.     

Polymeric implants for cancer chemotherapy

Cancer chemotherapy is not always effective. Difficulties in drug delivery to the tumor, drug toxicity to normal tissues, and drug stability in the body contribute to this problem. Polymeric materials provide an alternate means for delivering chemotherapeutic agents. When anticancer drugs are encapsulated in polymers, they can be protected from degradation. Implanted polymeric pellets or injected microspheres localize therapy to specific anatomic sites, providing a continuous sustained release of anticancer drugs while minimizing systemic exposure. In certain cases, polymeric microspheres delivered intravascularly can be targeted to specific organs or tumors. This article reviews the principles of chemotherapy using polymer implants and injectable microspheres, and summarizes recent preclinical and clinical studies of this new technology for treating cancer.     

药物洗脱支架时代的抗血小板治疗

药物洗脱支架降低了介入术后再狭窄的风险,但是也带来了对支架内血栓形成,特别是晚期和极晚期支架内血栓的担忧,这种担忧并不仅仅来自于长期随访得剑的流行病学数据,而是与DES的特定结构和作用机制密不可分的。     

Management of osteomyelitis

Early diagnosis and aggressive treatment, which includes thorough debridement and culture-directed antibiotic therapy, are essential for effective management of patients with osteomyelitis. Definitive diagnosis of osteomyelitis usually requires microbial culture of bone specimens obtained either by surgery or by percutaneous needle biopsy. The most common pathogen involved in osteomyelitis is Staphylococcus aureus; however, other organisms, including gram-negative pathogens and coagulase-negative staphylococci, may be found. Often, bone infections may be polymicrobial. Antimicrobial therapy, ideally initiated after complete surgical debridement and microbial confirmation of the diagnosis, is usually maintained for at least 6 weeks. Although therapy has traditionally been administered parenterally during an extended hospital stay, oral antibiotic therapy (often following initial parenteral therapy) and parenteral therapy on an outpatient basis are gaining acceptance for use in patients with osteomyelitis.     

Drug-eluting stents in peripheral vascular disease: eliminating restenosis

Transcatheter endovascular therapy for peripheral atherosclerotic disease has become more popular. In general, good results have been reported in focal aortoiliac disease. However, the long-term patency of angioplasty in longer, more distal lesions has been less satisfactory. Stenting has not been shown to improve long-term patency compared to angioplasty alone. Drug-eluting stents have shown promise in preventing coronary restenosis, and preliminary results in peripheral arterial disease are encouraging. This review article will discuss the current status of endovascular therapy of aortoiliac and femoropopliteal atherosclerotic disease, the theoretic and experimental basis for the use of drug-eluting stents, and the preliminary results in human studies.