透明质酸钠关节腔内注射治疗髋关节骨性关节炎的临床观察

目的 观察透明质酸钠关节腔内注射对髋关节骨性关节炎的治疗作用。方法 对20例髋关节骨性关节炎患者行透明质酸钠关节腔内注射,每周1次,连续5次。观察治疗前后关节疼痛、肿胀以及关节活动度等改善情况。结果 20例患者获得2～6月随访,临床缓解7例,显效8例,有效2例,无效3例。总有效率为85％。未见明显不良反应和感染发生。结论透明质酸钠关节腔内注射是一种安全、有效的髋关节骨性关节炎治疗方法。     

玻璃酸钠单独使用与联合使用复方倍他米松关节内注射治疗膝骨关节炎的疗效对比

目的:分别探讨玻璃酸钠及玻璃酸钠联合复方倍他米松关节内注射治疗膝关节骨关节炎的疗效。对比上述两种方法的疗效有无差异。探讨两种方法短期疗效与膝关节骨关节炎病情轻重有无关系。方法:选择膝关节骨关节炎病人80例,随机分为A组和B组,其中A组43个膝(双膝13例),治疗方法为玻璃酸钠(阿尔治)膝关节腔内注射,每次2.5mL,每周一次,5周为一疗程。B组62个膝(双膝12例),治疗方法为第一周膝关节内注射玻璃酸钠(阿尔治)2.5mL后,再注入复方倍他米松1mL。以后四周继续玻璃酸钠(阿尔治)膝关节腔内注射,每周一次,每次2.5mL。A组和B组治疗疗程结束后2周,根据L equesne等的有关膝关节OA病情严重性指数评估方法,制定相应观察表。对第一次治疗前及第5次治疗结束后2周膝关节进行评分,分别对A、B两组治疗前后评分进行配对t检验,之后对A、B两组治疗后评分进行两样本均数比较的t检验。计算改善率。根据治疗前评分分别将A、B组患者分为轻中度和重度两组,根据改善率将疗效分为有效和无效。使用组内分组的卡方检验对上述计数资料进行检验。结果:80例病人全部得到回访。A、B两组治疗前评分无显著性差异(P>0.05),A组治疗后评分与治疗前评分有显著性差异(P<0.01),B组治疗后评分与治疗前评分也有显著性差异(P<0.01)。A、B两组治疗后评分无显著性差异(P>0.05)。A组显效13例(缓解率≥75%),有效31例(缓解率<75%,≥30%),无效3例(缓解率<30%);B组显效16例,有效43例,无效3例。结果显示A、B两组治疗效果无显著性差异(P>0.05)。玻璃酸钠组(A组)对膝关节骨关节炎病情轻中度和重度的病人疗效无显著性差异(P>0.05)。玻璃酸钠组联合复方倍他米松组(B组)同样对膝关节骨关节炎病情轻中度和重度的病人疗效无显著性差异(P>0.05)。结论:关节腔内注射玻璃酸钠及复方倍他米松联合玻璃酸钠关节腔内注射具有较好的、相同的临床效能。两种方法的短期疗效与病情轻重无关。     

Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis

Osteoarthritis (OA) is the most common form of joint disease and a leading cause of physical disability, there is an urgent need to attenuate the progression of OA. Intra-articular (IA) injection is an effective treatment for joints diseases, however, the therapeutic effects mostly depend on the efficacy of drug duration in joints. Drug delivery system can provide drug-controlled release and reduce the number of IA injection. In this study, amphiphilic polyurethanes with pendant amino group were synthesized and amide bonds were formed between the amine group of polyurethane and the carboxyl group of kartogenin (KGN), a small molecular reported to show both regenerative and protective effects on cartilage. Our results showed that KGN-conjugated polyurethane nanoparticles (PN-KGN) were spherical and regular in shape with an average size of 25?nm and could sustained and controlled release of KGN in vitro. PN-KGN showed no cytotoxicity and pro-inflammatory effects on chondrocytes. The therapeutic effects in OA model showed that IA injection of KGN could attenuate the progress of OA, however, the cartilage degeneration became obviously at 12?weeks with matrix loss and vertical fissures. By contrast, IA injection of PN-KGN showed less cartilage degeneration with significant lower OARSI scores even at 12?weeks, indicating PN-KGN could further arrest the development of OA. Immunohistochemistry also validated that IA injection of PN-KGN retained the normal compositions of cartilage matrix, with much stronger Col II staining and less Col I staining. In conclusion, IA injection of PN-KGN is a better potential strategy to treat OA, with long-time cartilage protection and less IA injections.     

胰岛素肠溶PLGA纳米粒的制备及体内外性质的评价

目的制备肠溶胰岛素PLGA纳米粒,并对其理化性质、体外释药以及在正常大鼠体内的降血糖效果进行研究。方法采用改良的乳化溶剂扩散法分别制备了胰岛素PLGA纳米粒和肠溶胰岛素纳米粒(PLGA HP55 NP、PLGA HP50 NP)。通过激光粒度测定仪测定粒径大小,系统考察了肠溶材料HP55的用量及类型对纳米粒性质的影响,以及各种纳米粒在人工胃液、人工肠液中的释药行为和其在正常大鼠体内的降血糖作用,并与PLGA HP50 NP进行了比较。结果制得的最终处方的肠溶纳米粒(PLGA HP55)的粒径为(169±16)nm,胰岛素的载药量为(3.17±0.24)%。肠溶纳米粒在人工胃液中的释药速率明显低于PLGA纳米粒。PLGA纳米粒和肠溶PLGA HP50、PLGA HP55纳米粒均能显著降低正常大鼠的血糖浓度,其在正常大鼠体内24 h相对于皮下注射给药的相对生物利用度分别为(5.46±0.7)%、(6.31±0.64)%和(8.72±0.5)%。结论胰岛素肠溶纳米粒可以有效抑制胰岛素在人工胃液中的释放,与PLGA纳米粒相比显著降低正常大鼠的血糖浓度。其中PLGA HP55纳米粒的降糖作用显著高于PLGA HP50纳米粒。pH值高的纳米粒有望成为胰岛素口服给药的有效载体。     

Development of nanoparticles-in-microparticles system for improved local retention after intra-articular injection

Abstract

To increase the intra-articular (IA) retention time of osteoarthritis drugs in the synovial cavity and slow down the burst release of microspheres (MPs), we prepared a novel drug delivery system named nanoparticles-in-microspheres (NiMs). The system was constructed by dispersing the brucine-loaded nanoparticle, which was prepared by an emulsification method in the MPs. The NiMs were characterized by scanning electron microscope, Fourier transform infrared spectra and differential scanning calorimetry. After investigating the biocompatibility with synovium of NiMs in rats, the pharmacokinetics was studied and FX-imaging was used to visualize the transmission of nanoparticles after IA administration in rats. From the results, we know that the NiMs were spherical, there was no chemical bond between the drug and the polymer, and the drug was dispersed in the polymer in an amorphous form. Compared with MPs (41%), the burst release of NiMs could be slowed down to 9%. After that, the drug was released from NiMs by diffusion. The results of FX imaging in rats showed that the NiMs could stay in the articular cavity for over 11?d. The studies of pharmacokinetics revealed that the NiMs could slow down the burst release and improve retention in vivo. This study demonstrates the feasibility of using NiMs to slow down the burst release and increase the retention of therapeutic agents in articular joints.     

透明质酸治疗膝关节骨性关节炎的研究进展

骨关节炎是指多种原因引起的一种以关节软骨退行性病变和继发性骨质增生为特征的慢性关节病变,是世界范围内最常见的关节性病变。目前对于膝关节骨性关节炎的最佳治疗方法仍存较多争议。该文通过对膝关节骨性关节炎的治疗现状、发病机制及透明质酸治疗骨性关节炎的作用机制及临床研究进展,详细全面阐述透明质酸在治疗膝关节骨性关节炎中的研究进展,为临床治疗方案的选择提供依据。     

以纳米颗粒为载体转染基因的发展概况

目的综述以纳米颗粒作为基因载体进行基因治疗的发展概况。方法依据国内外刊物公开发表的文献,对有关以纳米颗粒作为基因递送载体进行基因治疗的研究进行分类、归纳与整理。结果纳米颗粒转运系统能够保护被转运的基因,有较高的转染效率,具有良好的靶向性,并且提高了药物的生物利用度,显示出一定的缓控释作用。结论纳米颗粒作为基因递送载体具有广阔的发展前景。     

玻璃酸钠关节腔注射治疗膝关节骨关节炎临床疗效研究

目的观察关节腔内注射玻璃酸钠治疗膝关节骨关节炎的临床疗效。方法以在本院就诊的膝关节骨关节炎患者为研究对象,共202只膝关节,关节腔内注射玻璃酸钠,每周1次,共5次,采用Lequesne膝关节功能及活动范围量表进行评分。结果总有效率达96．53％,随访半年后,10例患者复发,再行上述治疗,仍然有效。结论关节腔内注射玻璃酸钠是治疗膝关节OA的较理想的方法,操作简单、不良反应少、费用低,易于临床应用。     

The safety of intra-articular injections for the treatment of knee osteoarthritis: a critical narrative review

Introduction: International guidelines recommend that the management of knee osteoarthritis (OA) combine both nonpharmacological and pharmacological interventions. Intra-articular (IA) therapies are considered part of this multimodal approach and are well-established Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved treatments.

Areas covered: Safety data for knee OA, including IA corticosteroids, hyaluronic acid, platelet-rich plasma and botulinum toxin are critically reviewed, and evidence- and pratice-based measures to improve safety of IA therapies are discussed.

Expert opinion: The incidence of AEs attributable to IA therapies across clinical trials in knee OA is very low, and barely reaches significance when compared to the incidence of AEs in the comparator group. These events are exceptionally serious. Mild differences between products have been inconsistently reported mainly for IA HA. One can distinguish self-limited AEs such as post-injection pain and swelling that are the most frequently reported AEs, from AEs that are not self-limited but rare such as septic arthritis. The safety of IA therapies can be improved by applying simple measures designed to prevent AEs. However, even though no specific safety concerns have been raised to date about IA therapies, the quality of evidence is low, and there is a need to improve the monitoring and reporting of safety data from clinical trials and post-marketing surveillance.     

Production and in vitro characterization of lisinopril-loaded nanoparticles for the treatment of restenosis in stented coronary arteries

Lisinopril, an angiotensin converting enzyme (ACE) inhibitor drug, was encapsulated in poly(lactide-co-glicolide) (PLGA) nanoparticles (NP) for site-specific delivery by catheters in prevention of restenosis. NP were prepared by emulsification–diffusion method. The PLGA type, stabilizing agent type and its concentration were studied as process variables. The z-average particle size varied between 265–412 nm. The highest zeta potential was seen in NP prepared with Pluronic F-68. None of the studied variables or their interactions had a significant effect on the particle size while all had main effect on the zeta potential. The highest entrapment efficiency was 93% and all studied variables and their interactions except PLGA type and its interaction with the stabilizer type had significant effects on the loading. Baker-Lonsdale model was the most appropriate model for release of lisinopril from NP. Five per cent PLGA 75 : 25 and 5% Pluronic F-68 showed promising results for 21 days release of lisinopril as an anti-restenotic agent.     

国产与进口玻璃酸钠治疗膝关节骨关节炎疗效比较

目的 :比较进口与国产玻璃酸钠 (SH)治疗膝关节骨关节炎 (OA)的疗效。方法 :患OA病人 4 2例 ,分 2组 ,进口组 2 8例 ,男性 3例 ,女性 2 5例 ,年龄 58a±s 6a。国产组 14例 ,男性 3例 ,女性 11例 ;年龄 59a± 6a。进口与国产SH 2 5mg ,膝关节内注射 ,每周 1次 ,5次为一个疗程。结果 :按疼痛、炎症、活动障碍评估 ,进口组与国产组SH对OA均可改善上述症状 ,而进口组对疼痛改善优于国产组 ,P <0 .0 5。结论 :进口SH在治疗OA方面优于国产SH。     

Intra-articular drug delivery systems for osteoarthritis therapy: shifting from sustained release to enhancing penetration into cartilage

Osteoarthritis (OA) is a progressive chronic inflammation that leads to cartilage degeneration. OA Patients are commonly given pharmacological treatment, but the available treatments are not sufficiently effective. The development of sustained-release drug delivery systems (DDSs) for OA may be an attractive strategy to prevent rapid drug clearance and improve the half-life of a drug at the joint cavity. Such delivery systems will improve the therapeutic effects of anti-inflammatory effects in the joint cavity. Whereas, for disease-modifying OA drugs (DMOADs) which target chondrocytes or act on mesenchymal stem cells (MSCs), the cartilage-permeable DDSs are required to maximize their efficacy. This review provides an overview of joint structure in healthy and pathological conditions, introduces the advances of the sustained-release DDSs and the permeable DDSs, and discusses the rational design of the permeable DDSs for OA treatment. We hope that the ideas generated in this review will promote the development of effective OA drugs in the future.     

Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil

The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of ^99mTc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.     

玻璃酸钠关节腔注射治疗膝骨关节炎临床研究

目的：探讨玻璃酸钠关节腔注射治疗膝骨关节炎的临床疗效。方法：临床上符合膝骨关节炎诊断标准的60例患者。接受关节腔注射玻璃酸钠治疗,每周1次,5周为1个疗程。观察治疗前后患者的疼痛、膝关节活动情况。结果：60例中缓解18例（30％）,显效27例（45％）,有效9例（15％）,无效6例（10％）,有效率90％。治疗过程中未发现严重的毒副反应。结论：玻璃酸钠关节腔注射治疗膝骨关节炎的疗效确切,不良反应轻且少,值得推广应用。     

Formulation and evaluation of sustained release microspheres of poly-lactide-co-glycolide containing tamoxifen citrate

Tamoxifen citrate, a non-steroidal anti-oestrogen has potential applications in treatment of breast cancer. Biodegradable microspheres of' PLGA 65:35 were prepared by o/w emulsification solvent evaporation method. In this study, different batches of varying concentration of drug, polymer, polyvinyl alcohol and solvent were prepared. All the batches prepared were characterized by particle size distribution, encapsulation efficiency and in vitro release behaviour. Drug, polymer and PVA concentrations were varied to obtain optimum release profile for sustaining the action of drug.     

Formulation and optimization of celecoxib-loaded PLGA nanoparticles by the Taguchi design and their in vitro cytotoxicity for lung cancer therapy

Abstract

The objective of the present study was to develop, evaluate and optimize a polymeric nanoparticle (NP) system containing Cxb for pulmonary delivery of Cxb in the treatment of lung cancer. NPs were prepared by the emulsion solvent diffusion and evaporation method using poly(D, L lactideglycolide) (PLGA). The size of NPs ranged from 153 to 192?nm and was affected by PLGA content, surfactant concentration and organic phase volume. Zeta potential of NPs (?4.5 to ?8.6?mV) was more affected by PLGA content and organic phase volume. PLGA content was also the most effective factor on the entrapment efficiency and release rate of Cxb from NPs. The optimum formulation which obtained with 5?mg Cxb, 25?mg PLGA, 0.5% surfactant, 2.5% organic volume and 15?000?rpm showed release of Cxb within 30?h. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass medium aerodynamic diameter, geometric standard deviation of 70.3%, 1.46% and 3.38%, respectively. Our results provide evidence for the potential of PLGA NPs for delivery of Cxb through inhalation as means to alleviate the cardiovascular risk of Cxb administration.     

穴位注射联合中药综合疗法治疗膝骨性关节炎临床疗效观察

目的观察穴位注射联合中药综合疗法治疗膝骨性关节炎的临床疗效。方法将100例膝骨性关节炎患者随机分为治疗组和对照组各50例。治疗组采用穴位注射联合中药综合治疗,对照组口服氨基葡萄糖片、维生素C和美洛昔康片。2组均以1个月为1个疗程。治疗后比较2组临床疗效及症状总积分变化情况。结果治疗组治疗后X线分级Ⅰ级、Ⅱ级患者优良率高于对照组,差异有统计意义(P<0.05),2组总有效率比较差异无统计学意义(P>0.05)。治疗后2组症状总积分均较治疗前明显下降,治疗组X线分级Ⅰ级、Ⅱ级患者治疗后症状总积分低于对照组,差异均有统计学意义(P<0.05或P<0.01)。结论穴位注射联合中药综合疗法治疗膝骨性关节炎能有效改善临床症状。     

Targeted treatment for osteoarthritis: drugs and delivery system

The management of osteoarthritis (OA) is a clinical challenge due to the particular avascular, dense, and occluded tissue structure. Despite numerous clinical reports and animal studies, the pathogenesis and progression of OA are still not fully understood. On the basis of traditional drugs, a large number of new drugs have been continuously developed. Intra-articular (IA) administration for OA hastens the development of targeted drug delivery systems (DDS). OA drugs modification and the synthesis of bioadaptive carriers contribute to a qualitative leap in the efficacy of IA treatment. Nanoparticles (NPs) are demonstrated credible improvement of drug penetration and retention in OA. Targeted nanomaterial delivery systems show the prominent biocompatibility and drug loading-release ability. This article reviews different drugs and nanomaterial delivery systems for IA treatment of OA, in an attempt to resolve the inconsonance between in vitro and in vivo release, and explore more interactions between drugs and nanocarriers, so as to open up new horizons for the treatment of OA.     

New guidelines for topical NSAIDs in the osteoarthritis treatment paradigm

Abstract

Background:

Osteoarthritis (OA), the most common form of arthritis, often affects hands, hips, and knees and involves an estimated 26.9 million US adults. Women have a higher prevalence of OA, and the risk of developing OA increases with age, obesity, and joint malalignment. OA typically presents with pain and reduced function. Therapeutic programs are often multimodal and must take into account pharmaceutical toxicities and patient comorbidities. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with cardiovascular, gastrointestinal, and renal adverse events. Topical NSAIDs offer efficacy with reduced systemic drug exposure.     

臭氧联用透明质酸钠治疗膝关节骨性关节炎疗效

目的观察臭氧联用透明质酸钠(均外科用药)治疗膝关节骨性关节炎的临床疗效。方法住院病人178例,随机分为4组:单纯理疗组、单纯臭氧治疗组、单纯透明质酸钠治疗组和联合治疗组,同时给予补钙、保暖、适当功能锻炼等。其中联合治疗过程,先向关节腔内注射30μg.mL-1医用臭氧10～15 mL,每周注射1次,3次后使用透明质酸钠25 mg;5周为1个疗程。用SPSS13.0进行分析。结果研究人群有明显的功能改善;但治疗6,12个月比较无统计学意义(P>0.05)。经Womac评分与视觉模拟VAS评分,治疗后3个月后联合用药组效果最好。结论医用臭氧联合透明质酸钠注射剂可明显缓解膝关节骨性关节炎的疼痛症状、改善膝关节活动功能。