反相HPLC法测定马钱子中士的宁和马钱子碱的含量

建立反相高效液相色谱法测定马钱子中士的宁和马钱子碱的方法.色谱柱为Diammsil C18柱,以10mmol·L-1庚烷磺酸钠与20mmol·L-1磷酸二氢钾等量混合溶液(用10%磷酸调节pH值为2.8)-乙腈(79∶21)作为流动相,检测波长260nm;马钱子样品采用碱化后以氯仿回流提取.线性范围士的宁为0.4392～2.196μg、马钱子碱为0.3936～1.9680μg,士的宁回收率为100.90%,RSD为2.32%,马钱子碱回收率为102.57%,RSD为2.48%.本方法快速、准确、重现性好,可用于马钱子的质量控制.     

马钱子碱液关节腔内注射对兔膝关节损伤软骨的影响

目的探讨马钱子碱液关节腔内注射对兔膝关节软骨损伤的治疗效果。方法制作兔双侧膝关节软骨损伤模型,将30只兔子后肢按左右分为L、R两组。R组以1.701mg/mL的剂量关节腔内注射马钱子碱,每周1次连续5周,L组设为对照组,注射生理盐水。于药物干预后2周、4周、8周各处死10只兔子,取双侧膝关节行大体、组织学观察,根据关节软骨组织学计分标准进行评分。结果对药物干预后2、4、8周膝关节软骨组织大体观察及组织学计分标准评分结果显示:R组与L组修复差别有统计学意义(P<005)。结论马钱子碱稀释液关节腔内注射可促进软骨损伤的修复。     

应用反相高效液相色谱法测定马钱子胶囊中马钱子碱的血药浓度

用反相高效液相色谱法测定了马钱子碱的血药浓度,流动相为甲醇与0.0125M磷酸二氢钠(pH=5.6)检测波长为266nm,色谱柱为UltrasphereTMODS柱,线性范围为01～10.0ug/ml,日内变异系数为1.9～2.5%,日间变异系数为3.9%～6.2%,最低检测限为0.02ug。     

硝酸毛果芸香碱温敏凝胶的研制及溶蚀性能研究

目的制备硝酸毛果芸香碱温敏凝胶,考察其载药凝胶溶蚀行为。方法以泊洛沙姆为温敏凝胶基质制备硝酸毛果芸香碱眼用凝胶,通过凝胶相变温度筛选最佳处方,采用无膜溶蚀实验研究凝胶释药特性。结果18%、19%、20%的泊洛沙姆407溶液在体温范围内发生相变形成凝胶,其pH≈7,凝胶中硝酸毛果芸香碱释放速度分别为0.462、0.393、0.294 mg.min-1。结论18%-20%泊洛沙姆407溶液适合作为眼部给药的温敏凝胶基质,凝胶中药物释放基本符合零级释放行为。     

注射用粉防己碱温敏型缓释原位凝胶的制备

目的 制备以泊洛沙姆407(P407)为基本材料的注射用粉防己碱温敏型缓释原位凝胶,并考察其体外溶出行为.方法 采用冷溶法制备凝胶,以胶凝温度为指标,考察单独使用P407和加入其他辅料F188、PEG1500、HPMC、MC对胶凝温度的影响;采用无膜溶出法考察凝胶的体外溶蚀和释放行为,并采用HPLC测定溶出液中药物的含量,筛选较优处方.结果 胶凝温度随P407浓度的增大而降低;且当P407浓度低于15％时不发生相转变,辅料F188、PEG1500、MC的加入不能制备出符合要求的凝胶;8.0％、8.5％ 、9.0％ HPMC分别与8.0％ P407 混昆合制备凝胶的胶凝温度符合要求;HPMC浓度越高,药物释放越快,8.0％ HPMC和8.0％ P407混合后,胶凝温度和缓释效果均符合实验要求.结论 筛选出的处方中大大降低了P407的浓度,同时胶凝温度和缓释效果均符合实验要求,该温敏性凝胶具有良好的温度敏感性,制备方法简单可行.     

马钱子碱脂质体制备工艺研究

目的优化制备马钱子碱脂质体的处方.方法采用乙醇注入式硫酸铵梯度法制备马钱子碱脂质体;并以马钱子碱脂质体的包封率为主要评价指标,采用正交设计法优化马钱子碱脂质体的配方.结果获得了马钱子碱脂质体的工艺处方:卵磷脂与胆固醇的重量比为6∶1,马钱子碱和卵磷脂的重量比为1∶30,当硫酸铵浓度达到0.15 mol·L-1,卵磷脂的重量与硫酸铵溶液的体积比为12∶1.按该处方工艺制备3批马钱子碱脂质体,包封率平均值为92.17%.结论按照优化处方,可制得包封率稳定,粒径较小且分布较窄的马钱子碱脂质体.     

瘤内注射用醋酸奥曲肽温敏凝胶的质量评价

目的:评价自制瘤内注射用醋酸奥曲肽(OA)温敏凝胶的质量。方法:测定醋酸奥曲肽温敏凝胶的胶凝温度、黏度,采用反相高效液相色谱法测定样品中OA含量并考察其体外释放情况。结果:醋酸奥曲肽温敏凝胶的胶凝温度为(37.1±0.2)℃,在此温度下黏度为(4750±13)mPa·s,含量为5.1mg·mL-1,96h在磷酸盐缓冲液释放介质(pH=7.2)中体外累积释药率为(85.7±1.67)%。结论:醋酸奥曲肽温敏凝胶质量合格。     

复合载药微球壳聚糖温敏凝胶的初步研究

【摘要】目的 制备复合载药微球壳聚糖温敏凝胶（T-responsive CG/CMS）,观察其对牛血清蛋白的缓释效果,为负载外源性生长因子应用于牙周组织再生提供参考。方法 以牛血清蛋白为模型药物,利用离子凝胶法制备的牛血清蛋白壳聚糖微球,用扫描电镜观察其表面形态,测定药物载药量及包封率。并将牛血清蛋白壳聚糖微球共混于壳聚糖/β-甘油磷酸钠温敏凝胶体系形成T-responsive CG/CMS-BSA,并利用紫外分光光度计检测其对牛血清蛋白的缓释效果。结果 壳聚糖质量浓度在0.6~2.0 g/L,多聚磷酸钠质量浓度在0.5~1.0 g/L时均可生成形态较好,粒径均匀的壳聚糖微球。利用优化配方制备T-responsive CG/CMS在体温37 ℃发生溶胶到凝胶的转变,具有良好的温敏性能。体外释放试验表明T-responsive CG/CMS对牛血清蛋白的释放速度明显减慢,24 h累计释放率仅为16%,而单纯的壳聚糖温敏凝胶24 h累计释放率高达70%。结论 T-responsive CG/CMS对蛋白类药物具有良好的缓释作用,有望应用于牙周组织工程中生长因子的缓释。     

壳聚糖季铵盐温敏凝胶的制备及性能考察

目的 研究壳聚糖季铵盐温敏凝胶及性质.方法 采用试管倾斜法测定胶凝时间,考察壳聚糖季铵盐的浓度、体积比、温度等对胶凝时间的影响,采用吸光度经时变化法测定相变动力学,并用透析法测定载药凝胶的体外释放.结果 56％ GPS/2％ HTCC体积配比1:5、温度37℃时,胶凝时间为3.53min,钙黄绿素载药凝胶具有良好的缓释...     

盐酸布替萘芬阴道用温敏水凝胶的制备及体外释放度的考察

目的:制备盐酸布替萘芬阴道用温敏水凝胶并考察其体外释放度。方法:以泊洛沙姆为基质,筛选最佳处方以达到合适胶凝温度,并利用高效液相色谱法(HPLC)建立含量测定方法考察体外释放度。结果:结果显示以1%盐酸布替萘芬、0.1%山梨酸钾、2%甘油、5%聚山梨酯80、12%泊洛沙姆407及5%泊洛沙姆188为配方制备的温敏水凝胶在35℃时产生胶凝,体外释放度考察结果显示8 h可释放超过90%的药物。结论:本研究制备的盐酸布替萘芬阴道用温敏水凝胶具有很好的温度敏感性及黏附性,具有缓释特性且给药方便,是一种值得开发的药物制剂。     

Alginate nanogels-based thermosensitive hydrogel to improve antidepressant-like effects of albiflorin via intranasal delivery

Depression is a primary public health problem. However, current antidepressants work slowly, and together with side effects. Herein, the alginate nanogels were constructed to load albiflorin (albiflorin nanogels), which further formed albiflorin nanogel loaded self-assembled thermosensitive hydrogel system (albiflorin-NGSTH) and were used to improve its antidepressant effects. The nanogel showed a nano-scaled particle size and stronger antioxidant activity. Rheological studies showed that albiflorin-NGSTH had a sol-gel transition at approximately 28 °C. Albiflorin-NGSTH quickly entered the brain by intranasal delivery, and had a continuously release for albiflorin. Preliminary results of mice behavioral despair tests found that albiflorin-NGSTH had no effects on independent exploratory behavior and anxiety of the mice, and significantly decreased immobility duration of the mice in tail suspension test (TST). Moreover, the intranasally administrated albiflorin-NGSTH at a low dose improved depressive behavior, decreased levels of proinflammatory cytokines, and repaired neuronal damage of chronic unpredictable mild stress (CUMS) rats, which indicated an excellent potential for depression therapy. The treatment of albiflorin-NGSTH on depressive disorder was achieved by regulating signal pathway related to depression. Therefore, albiflorin-NGSTH has an excellent potential for clinical application in intranasal drug delivery systems.     

醋酸曲安奈德温敏凝胶药效学及滞留性

目的：制备关节腔注射用醋酸曲安奈德TAA温敏凝胶,考察其药效学和滞留性。方法：采用物理混合法制得TAA温敏凝胶,建立老鼠皮下气囊炎症模型,给予不同组分药物治疗后,通过对比皮下囊物理特征、组织切片的相关评价以及elisa试剂盒检测炎性因子TNF-α水平等来考察所制备的TAA温敏凝胶药效学及缓释性能,并通过小动物活体成像实验评价其滞留性。结果：药效学结果显示制备的TAA温敏凝胶相比于市售TAA混悬液对于气囊滑膜炎模型的炎症抑制作用更强、作用时间更持久。小动物活体成像实验结果显示制备的TAA温敏凝胶在体内滞留时间能达到9 d以上,能够达到缓释药物的目的,适用于关节腔局部用药的要求。结论：所制备的TAA温敏凝胶的炎症抑制作用强且持久,缓释效果及滞留性良好,有望成为新的关节腔给药传递系统。     

Smart thermosensitive chitosan hydrogel for nasal delivery of ibuprofen to treat neurological disorders

Background: The in-situ gelation of thermosensitive nasal formulations with desirable spray characteristics at room temperature and ability to undergo a phase change to a semi-solid state with mucoadhesive behavior at physiological temperature has the potential to efficiently deliver therapeutics to brain. However, their application in nasal spray generation with favorable characteristics has not been investigated.

Methods: Thermosensitive chitosan (CS)-based formulations with different viscosities were prepared for intranasal delivery of ibuprofen using CS of various molecular weights. The formulation developed was optimized with regards to its physicochemical, rheological, biological properties and the generated aerosol characteristics.

Results: The formulations showed rapid gelation (4–7 min) at 30–35°C, which lies in the human nasal cavity temperature spectrum. The decrease in CS molecular weight to 110–150 kDa led to generation of optimum spray with lower Dv₅₀, wider spray area, and higher surface area coverage. This formulation also showed improved ibuprofen solubility that is approximately 100× higher than its intrinsic aqueous solubility, accelerated ibuprofen transport across human nasal epithelial cells and transient modulation of tight junctions.

Conclusions: A thermosensitive CS-based formulation has been successfully developed with suitable rheological properties, aerosol performance and biological properties that is beneficial for nose-to-brain drug delivery.     

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.     

Vaginal delivery of carboplatin-loaded thermosensitive hydrogel to prevent local cervical cancer recurrence in mice

Local tumor recurrence after cervical cancer surgery remains a clinical problem. Vaginal delivery of thermosensitive hydrogel may be suited to reduce tumor relapse rate with more efficacy and safety. A pilot study was carried out to evaluate the efficacy of carboplatin-loaded poloxamer hydrogel to prevent local recurrence of cervical cancer after surgery. In vivo vaginal retention evaluation of 27% poloxamer hydrogel in mice was proven to be a suitable vaginal drug delivery formulation due to its low gelation temperature. A mimic orthotopic cervical/vaginal cancer recurrence model after surgery was established by injecting murine cervical cancer cell line U14 into the vaginal submucosa to simulate the residual tumor cells infiltrated in the surgical site, followed by drug administration 24?h later to interfere with the formation/recurrence of the tumor. By infusing fluorescein sodium-loaded hydrogel into the vagina of mice, a maximized accumulation of fluorescein sodium (Flu) in the vagina was achieved and few signals were observed in other organs. When used in the prevention of the cervical cancer formation/recurrence in mice, the carboplatin-loaded poloxamer hydrogel exhibited great efficacy and systemic safety. In conclusion, thermosensitive hydrogel presents a simple, practical approach for the local drug delivery via vagina against cervical cancer recurrence.     

Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect

The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32 °C. This SLN gave the mean particle size of about 190 nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25 °C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35 °C existed as liquid at room temperature, but gelled at 30–36 °C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and C_max value compared to the hydrogel due to reduced initial burst effect. No damage in rectal mucosa was observed after the application of DRTH. Thus, this DRTH system with improved bioavailability and reduced initial burst effect would be recommended as an alternative for the flurbiprofen-loaded rectal pharmaceutical products.     

Biodegradable thermosensitive copolymer hydrogels for drug delivery

Biodegradable thermogelling copolymer hydrogels have great applicative potential in areas such as sustained drug release, gene delivery and tissue engineering. These injectable materials can be implanted in the human body with minimal surgical intervention. The thermosensitive copolymers have been incorporated with a variety of biocompatible and biodegradable components such as poly(D,L-lactic acid-co-glycolic acid), poly(L-lactic acid), poly (L-carprolactone), poly([R]-3-hydroxybutyrate), poly(organophosphazene), poly(peptide), poly(propylene fumarate), poly(propylene phosphate), polyacetal and poly(ortho ester). Various formulations consisting of the copolymers and therapeutic agents have been developed and the sustained release of these agents has been demonstrated. This review aims to provide a comprehensive summary of the recent developments in this field of study and highlights the most recent intellectual property and research papers.