Cationic solid lipid nanoparticles (cSLN): structure, stability and DNA binding capacity correlation studies

Cationic solid lipid nanoparticles (cSLN) are promising lipid nanocarriers for intracellular gene delivery based on well-known and widely accepted materials. cSLN containing single-chained cationic lipid cetyltrimethylammonium bromide were produced by high pressure homogenization and characterized in terms of (a) particle size distribution by photon correlation spectroscopy (PCS) and laser diffractometry (LD), (b) thermal behaviour using differential scanning calorimetry (DSC) and (c) the presence of various polymorphic phases was confirmed by X-ray diffraction (WAXD). SLN composed of Imwitor 900P™ (IMW) showed different pDNA stability and binding capacity in comparison to those of Compritol 888 ATO™ (COM). IMW-SLN, having z-ave = 138-157 nm and d(0.5) = 0.15-0.158 μm could maintain this size for 14 days at room temperature. COM-SLN had z-ave = 334 nm and d(0.5) = 0.42 μm on the day of production and could maintain similar size during 90 days. IMW-SLN revealed improved pDNA binding capacity. We attempted to explain these differences by different interactions between the solid lipid and the tested cationic lipid.     

泊洛沙姆407修饰对聚乙烯亚胺的毒性和转染性质的影响

目的:考察泊洛沙姆407修饰对聚乙烯亚胺(PEI)的毒性和转染性质的影响.方法:使用琥珀酰亚胺碳酸脂法将P407连接在PEI的氨基上,得到新聚合物,通过1H-NMR确定新聚合物的结构,将该聚合物与DNA形成复合物,测定复合物的zeta电位,MTT法考察复合物的细胞毒性,使用质粒pGL3-lus作为报告基因,测定虫荧光素酶活性评价复合物对Hela细胞的转染效率.结果:1H-NMR结果表明合成的聚合物具有较高的纯度.复合物的Zeta电位随氮/磷比(N/P)值的增加而增高.复合物的细胞毒性随着N/P值的增加而增大,新聚合物其细胞毒性显著低于未修饰的PEI.新聚合物在高N/P值时仍能保持较高的转染效率.结论:泊洛沙姆407修饰的PEI可以作为一种有效的非病毒基因栽体.     

无膜释放模型考察直肠用温敏型原位凝胶的体外释放情况

目的:研究直肠用温敏型原位凝胶的体外释药考察方法。方法:采用无膜释放模型,以对乙酰氨基酚为模型药物、泊洛沙姆407为基质制备凝胶;分别采用《中国药典》桨法和常见的水浴振荡法,考察桨法转速(50、75、100r·min-1)、振荡器振荡频率(50、100、150r·min-1)对凝胶中药物释放行为的影响,并对释药数据采用不同的方程进行拟合。结果:桨法释药速率随桨速的增加而加快,但不同桨速间释药行为存在一定差异;振荡法释药速率也随振荡频率的增加而加快,但释药行为基本相似。各释药行为均符合零级方程,并以桨法75r·min-1和振荡法100r·min-1最符合。结论:本文建立的无膜释放模型可用于以泊洛沙姆407为基质的温敏型原位凝胶的释药研究,且桨法宜采用转速为75r·min-1,振荡法宜选用振荡频率为100r·min-1。     

Alginate-poloxamer microparticles for controlled drug delivery to mucosal tissue

Purpose: The aim of this study was to prepare and characterize novel hydrogel-based delivery systems allowing for the controlled release of drugs to mucosal surfaces. Methods: Terbutaline sulfate and bovine serum albumin (BSA)-loaded alginate-poloxamer microparticles were prepared by a w/o-emulsion- and external gelation method. The microparticles were characterized by optical and scanning electron microscopy, laser light diffraction, atomic absorption spectroscopy, energy-dispersive X-ray analysis, via complexation with 1,9-dimethyl methylene blue and using dialysis bags as well as modified Franz diffusion cells for in vitro drug-release measurements. Results: Using heptane as organic phase, homogeneous and almost spherical microparticles were obtained with a high-loading efficiency (>90%). The resulting drug-release patterns could effectively be adjusted by varying the “alginate:poloxamer” blend ratio. In addition, the particle size, morphology, calcium and chloride content as well as alginate-release rates could be altered. Erosion was the predominant release mechanism for BSA. Special attention needs to be paid to the microparticle recovery procedure, which can significantly affect key properties such as the resulting drug-release patterns. Conclusions: The novel hydrogel-based microparticles offering mild conditions for incorporated drugs (e.g., proteins) provide an interesting potential as controlled delivery systems for mucosal surfaces.     

缓释载药体泊洛沙姆407圆窗灌注对耳蜗结构与听觉功能的影响

目的观察圆窗局部灌注泊洛沙姆407对耳蜗功能和结构的影响。方法16只健康豚鼠右耳圆窗灌注100μl20％泊洛沙姆407溶液作为实验组,左耳灌注生理盐水作为对照组,另取4只动物不予处理作为阴性对照组。于灌注前、后及灌注后第7、14、28及49d行听性脑干诱发电位（auditorybrainstemresponse,ABR）检测,并于检测后分别处死4只动物,行耳蜗基底膜铺片并计数。结果泊洛沙姆407灌注后ABR阈值较灌注前均有所提高,但在49d时恢复至灌注前水平;耳蜗毛细胞计数显示泊洛沙姆407圆窗灌注后无明显毛细胞缺失。结论泊洛沙姆407圆窗灌注对ABR阈值有暂时性影响,但未对耳蜗功能和结构起到持久性不可逆性损伤,符合中、内耳疾病的缓释给药治疗的条件。     

A Novel Mucoadhesive Polymer Film Composed of Carbopol,Poloxamer and Hydroxypropylmethylcellulose

Using the casting method novel mucoadhesive polymer blend film consisting of Carbopol, poloxamer, and hydroxypropylmethylcellulose (HPMC) was prepared and characterized. Triamcinolone acetonide (TAA) was loaded into Carbopol/poloxamer/HPMC polymer blend film. Carbonyl band of Carbopol in Carbopol/poloxamer/HPMC shifted to longer wavenumber than that of Carbopol in Carbopol/poloxamer due to the hydrogen bonding among Carbopol, poloxamer, and HPMC. Tan delta peak assigned to glass transition temperature (Tg) of HPMC shifted to low temperature due to increased flexibility caused by increased poloxamer content in polymer blend films. Swelling ratio of Carbopol/poloxamer/HPMC films was lowest in Carbopoll poloxamer/HPMC at mixing ratio of 35/30/35 (wt/wt/wt). Adhesive force of Carbopol/poloxamer/HPMC films increased with increasing HPMC content in Carbopol/poloxamer/HPMC polymer blend film and increasing hydroxypropyl group content in HPMC due to hydrophobic property of HPMC although bioadhesive force was highest at mixing ratio of 35/30/35 (wt/wt/ wt). Release of TAA from TAA-loaded Carbopol/poloxamer/HPMC polymer blend film in vitro increased with increasing loading content of drug.     

pH值对蔗糖酯类声学造影剂制备的影响

目的研究不同pH值PBS缓冲液对蔗糖酯-泊洛沙姆声学造影剂制备的影响。方法将蔗糖酯SE-5和泊洛沙姆188按1：1质量比,先后混溶于不同pH值的PBS缓冲液中。对不同pH值溶液均以400w声振功率及60s声振时间进行声振处理。光学显微镜下观察并记录声振后溶液内生成微泡的浓度及粒径大小。结果微泡数量随PBS缓冲液pH值增大而增多,微泡粒径随pH值增大而减小,pH值7．6时为微泡较佳生成条件。结论pH值对蔗糖酯类声学造影剂微泡数量及粒径整体有显著影响,以pH值7．6为较佳制备条件。     

Evaluation of Selected Micronized Poloxamers as Tablet Lubricants

The primary objective of this study was to compare the lubrication properties of micronized poloxamer 188 (Lμ trol micro 68®) and micronized poloxamer 407 (Lμ trol micro 127®) with certain conventional lubricants such as magnesium stearate and stearic acid. The secondary objective was to use these micronized poloxamers as water-soluble tablet lubricants in preparation of effervecsent tablets. The results showed that these micronized poloxamers have superior lubrication properties compared with stearic acid, with no negative effect on tablet hardness, friability, disintegration, or dissolution. Moreover, lubricant mixing time had no significant effect on tablet properties when poloxamers were used as lubricants. Effervescent tablets also were produced successfully using micronized poloxamers as lubricants. The micronized poloxamers had a better lubrication effect in compariason with that of water-soluble lubricant l-leucine.     

A comparison of different surfactants on foam stability in foam sclerotherapy in vitro

Objective

This article compares the effect of different surfactants on foam stability and determines the foam decay relationship, so that the suitability of surfactants in a clinical setting can be evaluated.

Effect of poloxamer on the dissolution of felodipine and preparation of controlled release matrix tablets containing felodipine

The effects of poloxamer and HPMC on the dissolution rate of felodipine were investigated and a felodipine controlled release tablet was developed by increasing the water solubility of felodipine and using swelling polymer to control release rate. Milling of felodipine slightly increased the dissolution rate of felodipine when compared with physical mixture. XRD results indicated that felodipine remained in the crystalline form even after co-milling with poloxamer. Improved dissolution rates after co-milling with HPMC and poloxamer were due to both solubilization effect of polymer and milling. The effect of poloxamer on dissolution rate was more significant than that of HPMC. Based on increased solubility of felodipine in the presence of poloxamer, it was concluded that the improved dissolution rate of felodipine was mainly due to a high local concentration of poloxamer around felodipine. Controlled release felodipine tablets were prepared using poloxamer as a solubilizing agent and Carbopol as a controlled release matrix.