盐酸小檗碱泊洛沙姆188固体分散体的制备

目的:制备盐酸小檗碱泊洛沙姆188固体分散体。方法:采用熔融法制备固体分散体,考察药物和载体的比例、熔融温度、冷却温度对溶出率的影响,比较固体分散体和物理混合物的溶出率的区别。结果:药物和载体比例达到1∶1时,载体的量足够使药物分散均匀;熔融温度对溶出率影响不大;冷却温度对溶出率影响较大,0℃时溶出率最快。与物理混合物相比,固体分散体将盐酸小檗碱的溶出率提高了近1倍。结论:盐酸小檗碱泊洛沙姆188固体分散体提高了盐酸小檗碱的体外溶出率。     

Cyclosporine a-nanosuspension: formulation, characterization and in vivo comparison with a marketed formulation

Cyclosporine A-nanosuspensions were prepared using zirconium oxide beads as a milling media, Poloxamer 407 as a stabilizer and distilled water as an aqueous medium using the Pearl Milling technique. The optimized formulation was characterized in terms of particle size distribution, surface morphology, drug-surfactant interaction, drug content, saturation solubility, osmolarity, and stability. The nanoparticles consisting of Poloxamer-bound cyclosporin A with a mean diameter of 213 nm revealed a spherical shape and 5.69 fold increased saturation solubility as compared to the parent drug. The formulation was found to be iso-osmolar with blood and stable up to 3 months at 2–8°C. In-vivo studies were carried out in albino rats and the pharmacokinetic parameters were compared with a marketed formulation, which indicated better results of the prepared formulation than the marketed one.     

Effect of Poloxamer-Based Thermo-Sensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial

PurposeRestricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND.MethodsWe designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period).ResultsA total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (−30.04 ± 27.76 vs. −42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (−3.92 ± 9.80 vs. −10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group.ConclusionWe suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02967146","term_id":"NCT02967146"}}NCT02967146     

Effect of various poloxamer coatings on in vitro adhesion of isohexylcyanoacrylate nanospheres to rat ileal segments under liquid flow

This work evaluates the bioadhesive properties of isohexylcyanoacrylate nanocapsules coated with poloxamers 407, 238, 403 and poloxamine 908 compared to nanoparticles coated with poloxamer 407. Nanocapsules (oil droplets surrounded by a polymeric wall) and nanoparticles (plain polymeric spheres) were prepared, labelled with covalently linked with tetraiodinated ¹²⁵I-phthalocyanine-Zn and laid on the rat ileal segment in vitro. After 0 and 10 min following transfer of nanospheres, a liquid flow was started. In all cases studied, a fraction of the nanospheres was not adherent when perfusion was initiated and was recovered in the first fraction. The other fraction, representing approx. 45% of the nanospheres, adhered firmly and was removed very slowly by the liquid flow. In addition, when nanocapsules were coated with poloxamers 238 and 407, the percentage adhesion increased between and 10 min. Our results demonstrate that the greatest extent of mucoadhesion was achieved with poloxamers possessing a short centra polyoxypropylene (POP) chain and long polyoxyethylene (POE) side chains. The results are discussed on the basis of diffusion of the POE groups into the mucin network and creation of secondary chemical adhesive bonds (Van der Waals type) between the nanosphere coating and mucus.     

Protein adsorption patterns on poloxamer- and poloxamine-stabilized solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) were produced using a full range of poloxamer polymers and poloxamine 908 for stabilization. The protein adsorption pattern acquired on the surface of these particles after intravenous injection is the key factor determining the organ distribution. Two-dimensional polyacrylamide gel electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. The objective of this study was to investigate changes in the plasma protein adsorption patterns in the course of variation of the polymers stabilizing the SLN. Considerable differences in the protein adsorption with regard to preferential adsorbed proteins were detected for the different stabilizers. Possible correlations between the polyethylene oxide (PEO) chain length and the adsorption of various proteins (first of all apolipoproteins) are shown and discussed. Besides the study of protein adsorption patterns, the total protein mass adsorbed to the SLN was also evaluated using the bicinchoninic acid (BCA)-protein assay. The knowledge concerning the interactions of proteins and nanoparticles can be used for a rational development of particulate drug carriers. Based on the findings presented in this paper, we anticipate that the in vivo well-tolerable SLN are a promising site-specific drug delivery system for intravenous injection.     

利巴韦林鼻用温敏凝胶热力学和流变学性质研究

考察了不同浓度泊洛沙姆407、PEG6000和泊洛沙姆188及处方量利巴韦林对鼻用温敏凝胶的热力学[胶凝温度（T1）、胶融温度（T2）]和流变学性质（黏度）的影响。结果表明，凝胶的T1和黏度均与泊洛沙姆407浓度呈负相关，而T2则与其呈正相关；利巴韦林和相应辅料对凝胶的T1、T2和黏度都有不同程度的影响。     

Determination of poloxamer 188 and poloxamer 407 using high-performance thin-layer chromatography in pharmaceutical formulations

Poloxamers (PXMs) are amphiphilic non-ionic block polymers commonly used in the cosmetic and pharmaceutical industries. In spite of the wide use of PXMs, few studies have dealt with the analysis of these polymers in pharmaceutical preparations. In this work, high-performance thin-layer chromatography (HPTLC) has been used to quantify both PXM-188 and PXM-407 in pharmaceutical preparations. The separation of these compounds was carried out using reverse phase HPTLC plates with a chloroform-methanol mixture as the mobile phase. Detection was performed densitometrically using the Dragendorff's reagent for the visualization of PXMs. Quality parameters were established, and the detection limits ranged from 24 to 47ng/spot. A good precision (day to day and run to run), with relative standard deviations <11.18%, was obtained. The proposed method was satisfactorily applied to the analysis of laboratory-made and commercial pharmaceutical products.     

三氧化二砷-泊洛沙姆４０７缓释剂瘤内注射治疗裸鼠人肝癌移植瘤的实验研究

目的：观察三氧化二砷-泊洛沙姆４０７（Ａｓ_２Ｏ_３-Ｐ４０７）缓释剂对裸鼠皮下人肝癌移植瘤的有效性。方法：以人肝癌ＨｅｐＧ２细胞为来源建立裸鼠皮下移植瘤模型,实验共分３组：Ａｓ_２Ｏ_３-Ｐ４０７缓释剂治疗组、Ａｓ_２Ｏ_３治疗组和生理盐水（ＮＳ）对照组,于造模成功后６～８天行瘤体注射,每４天１次,共４次。比较各组抗癌疗效,观察裸鼠体重、肿瘤体积变化、抑瘤率、肿瘤组织病理及骨髓涂片以及裸鼠的存活情况、生存质量。结果：Ａｓ２Ｏ３ Ｐ４０７缓释剂治疗组肿瘤生长受到显著抑制,肿瘤体积较Ａｓ_２Ｏ_３组小（Ｐ＜０.０５）,瘤重分别为（０.２５７±０.０８０）ｇ和（０.６４１±０.１０９）ｇ,差异有统计学意义（Ｐ＜０.０５）;两组与ＮＳ对照组瘤重（１.０９４±０.１４７）ｇ相比,差异有统计学意义（Ｐ＜０.０５）。治疗后Ａｓ_２Ｏ_３-Ｐ４０７缓释剂组裸鼠体重大于Ａｓ_２Ｏ_３组和ＮＳ对照组,差异有统计学意义（Ｐ＜０.０５）。各组均未见骨髓抑制现象。结论：Ａｓ_２Ｏ_３-Ｐ４０７缓释剂瘤内注射,使用安全,可维持局部有效药物浓度、延长作用时间,疗效优于Ａｓ_２Ｏ_３注射液。     

穿心莲有效部位Poloxamer188聚合物胶束的制备工艺

目的制备Poloxamer188穿心莲有效部位的聚合物胶束。方法薄膜水化法制备穿心莲有效部位聚合物胶束,正交设计优化处方工艺。HPLC法测定其载药量和包封率,激光粒度仪测定粒径。结果载药胶束包封率为(85.7+2.1)%,载药量为(1.11+0.09)%,粒径为(198.32+3.35)nm。结论载药Poloxamer188胶束制备工艺简便易行,为中药制剂提供了新剂型。     

In Vitro Antileishmanial Activity of Amphotericin B Loaded in Poly(ε-Caprolactone) Nanospheres

The activity of formulations for amphotericin B (AmB) associated with poly (ε -caprolactone) nanospheres and coated with variable amounts of a non ionic surfactant poloxamer 188, was evaluated against AmB-susceptible (WT) and AmB-resistant (AmB r) strains of Leishmania donovani amastigotes in thioglycolate-elicited peritoneal macrophages. AmB-nanospheres were more actives than free AmB only against amastigotes of wild strain. The activity was not influenced by the concentration of poloxamer 188 used to stabilize the nanospheres in spite of this surfactant was previously reported to synergy with AmB on the membrane of the resistant parasite. Similarly, this improvement was not mediated through macrophage activation. In fact, these nanoparticle formulations appeared to inhibit both NO and TNF- α production induced by the free drug. Therefore, we suggest that the association of AmB with nanospheres may improve the capability of the drug to interact with ergosterol. This hypothesis appears to be supported by the fact that nanospheres did not show any improvement of the AmB activity against the resistant strain (characterized by the absence of ergosterol).