The effects of Pluronic block copolymers on the aggregation state of nystatin.

The purpose of this work was to characterize the effect of block copolymer composition on the aggregation state of nystatin in the presence of Pluronic micelles. The critical aggregation concentrations (CACs) of nystatin were determined by dynamic light scattering (DLS). The CAC of nystatin in phosphate-buffered saline was 20 microM at 37 degrees C. Addition of Pluronics significantly increased the CAC of nystatin up to >350 microM at 37 degrees C at the concentrations studied. The CAC values corresponded directly to the size of the Pluronic hydrophobic blocks, and inversely with Pluronic critical micellization concentration (CMC). Predictably, increasing Pluronic concentration and temperature revealed increases in CACs. The micelle-water partition coefficient (P) of nystatin was determined by nystatin fluorescence. The P for nystatin at 37 degrees C was calculated in F68, F98, P105, and F127 to be 15, 21, 73, and 79, respectively. Pluronic micelle core polarity experiments, determined by pyrene fluorescence, revealed decreased polarity with increasing hydrophobic block length and temperature. Thus, nystatin CACs in the presence of Pluronics correlated directly with the partition coefficients, and inversely with core polarity. These results point to the number of micelles in solution as the primary factor responsible for nystatin solubilization by Pluronics.     

Pluronic F127 gel formulations of deslorelin and GnRH reduce drug degradation and sustain drug release and effect in cattle.

The objective of this study was to compare the effectiveness of intramuscular sustained release Pluronic F127 (PF127) gel formulations of deslorelin, a potent GnRH agonist, and GnRH to their solution formulations in inducing the release of luteinizing hormone and formation of luteal tissue in cattle. Injectable gel formulations of deslorelin and GnRH were prepared using Pluronic F127 (25%, w/w), a block copolymer. PF127 gels sustained the in vitro release of deslorelin as well as GnRH at similar rates and reduced drug degradation in muscle tissue when compared to the solution formulations. Deslorelin, as well as GnRH, elicited desirable elevations in plasma LH and progesterone concentrations in vivo. When compared to the solution formulations, the gel formulations of both drugs induced a broader peak of LH. Also, the peak LH levels were lower and the peak times were delayed with the gel formulations compared to the solution formulations. While the solution dosage form of deslorelin and GnRH elicited similar responses, the PF127 gel formulation of deslorelin induced peak LH levels at an earlier time (3 h for deslorelin versus 5.25 h for GnRH). The results indicate that, deslorelin exerts a pharmacological effect in cattle. The LH response to deslorelin as well as GnRH can be altered by controlling the input or the release rate of the drug. PF127 gel formulations can sustain peptide release and reduce peptide degradation.     

Optimization of a thermally reversible W/O/W multiple emulsion for shear-induced drug release.

PURPOSE: The present work aimed at improvement of the formulation of a previously developed thermo-reversible W/O/W multiple emulsion by increasing the emulsion stability and reaching a higher fraction of an encapsulated drug released under shear. The emulsion was based on high molecular weight graft-copolymers of poly(acrylic acid) and Pluronic F127 as stabilizing agents. METHODS: Once a stable W/O/W thermo-reversible multiple emulsion was obtained via a fine-tuning of the formulation, rheological, granulometric and conductometric tests were performed to assess the thermo-reversible behavior and the fragmentation-release characteristics of the new W/O/W multiple emulsion. RESULTS: The emulsion exhibited a 10(3) fold increase in viscosity over a range of temperatures from 20 to 40 degrees C. At moderate shearing, a complete release of the marker encapsulated in the internal aqueous phase was observed (99.6%) at 35 degrees C, whereas only 30% was released at 20 degrees C. Under similar conditions at 35 degrees C, slightly more than 50% was released for the initial formula. CONCLUSION: Additionally, the ease of fabrication of the thermo-reversible W/O/W multiple emulsion combined with the complete release under shear at body temperature and the superior emulsion stability suggest numerous applications in the controlled release of drugs.     

Pluronic F 127 liquid sensitizes mice to low doses of Escherichia coli lipopolysaccharide.

BACKGROUND AND METHODS: In murine models of endotoxemia, large amounts of lipopolysaccharide have to be administered to induce mortality. If mice are pretreated with D-galactosamine, the amount of lipopolysaccharide required to induce mortality is significantly lowered. Pluronic F 127 liquid is a relatively non-toxic copolymer that exhibits reverse gelation properties. Thus, it is a liquid at cold temperature and a gel at body temperature. The present studies were performed to ascertain whether the reverse gelation properties of Pluronic F 127 liquid could be used in devising a model of septic shock where a sustained delivery of lipopolysaccharide occurred. In evaluating this model, dose-response studies were conducted with lipopolysaccharide when a) it was administered intraperitoneally in saline or in Pluronic F 127 liquid, and b) it was administered intravenously to mice that had been pretreated with saline or Pluronic F 127 liquid. Mortality was followed for up to 72 hrs. RESULTS: Various doses of Escherichia coli lipopolysaccharide dissolved in saline or in Pluronic F 127 liquid were administered intraperitoneally to mice. The lethal dose of lipopolysaccharide required to kill 50% of the mice (LD50) administered in Pluronic F 127 liquid was approximately ten- to 15-fold less than the values obtained for lipopolysaccharide administered in saline. This decrease in the LD50 of lipopolysaccharide was also observed if the mice were treated intraperitoneally with Pluronic F 127 liquid and challenged 6 hrs later with iv lipopolysaccharide. The concentrations of tumor necrosis factor and interleukin-6 in the plasma were significantly higher when a low dose of lipopolysaccharide was administered to mice that had been pretreated with Pluronic F 127 liquid. While there was no effect on the liver enzymes, Pluronic F 127 liquid caused an increase in the plasma triglycerides. CONCLUSIONS: The data reported in this paper indicate that the LD50 of lipopolysaccharide is significantly decreased if it is administered in Pluronic F 127 liquid or administered to mice that have been pretreated with the Pluronic F 127 liquid. Thus, Pluronic F 127 liquid appears to sensitize mice to low levels of lipopolysaccharide. Unlike the D-galactosamine model, lipopolysaccharide can be administered as late as 6 hrs after treatment with Pluronic F 127 liquid. While the mechanisms by which Pluronic F 127 liquid sensitizes mice is not known, plasma triglycerides were increased in mice treated with this agent, suggesting that tissues responsible for the synthesis and/or degradation of triglycerides play a role in this sensitization process.     

Temperature-controlled content release from liposomes encapsulating Pluronic F127.

Temperature-dependent internal content release from liposomes was examined using di-oleoylphosphatidylcholine (DOPC)/cholesterol liposomes with encapsulated Pluronic F127 molecules. The interaction of Pluronic F127 with the lipid bilayer at elevated temperature causes the release of encapsulated contents. Content release was measured using fluorescent markers of two different sizes: small, carboxyfluorescein (CF), and large, bovine serum albumin-conjugated fluorescein iso-thiocyanate (BSA-FITC). Release of CF was studied using fluorescence de-quenching, while that of BSA-FITC was studied using fluorescence emission quenching due to fluorescence resonance energy transfer (FRET). Temperature-controlled complete internal content release was achieved at a precise temperature by controlling the concentration of the encapsulated Pluronic. Increasing cholesterol % in the liposome composition resulted in a sharper transition with temperature in content release. The onset temperature of content release increased with decrease in Pluronic concentration. For the same Pluronic concentration, the onset temperature also depended on the size of the encapsulated marker and was higher for larger markers. We have established that onset of content release is determined by the critical micellar temperature (CMT) of the Pluronic. Temperature-sensitive liposomes, made stealth using di-stearoyl(polyethylene glycol 5000) phosphatidylethanolamine (DSPEG5000PE) in conjunction with Pluronic F127, had similar temperature sensitivity and efficiency in content release compared to the non-stealth liposomes.     

The effect of solutes and polymers on the gelation properties of pluronic F-127 solutions for controlled drug delivery

The effect of solutes (benzoic acid and para-hydroxybenzoate esters) and water-soluble polymers (poly(ethylene glycol) s, PEGs) on the gel-sol transition temperature of Pluronic F-127 solutions has been characterised. The solutes produced a decrease in aqueous PF-127 gelation temperature, an effect shown to be dependent upon solute concentration and physicochemical properties. PEG increased the gelation temperature of PF127 solutions, the extent of the increase depending on PEG chain length and concentration. Simultaneous addition of bemoic acid and PEG produced an intermediate gelation temperature. This enables the formulation of a PF-127 solution of which the gelation properties can be controlled, while increasing the solute loading capacity.     

Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization.

Here we investigated thermo-sensitive Pluronic(R) F127 (PF127) hydrogel for the controlled release of peptide and protein drugs after subcutaneous injection, using an antithrombotic polypeptide, recombinant hirudin variant-2 (rHV2), as the model drug. The in vitro release experiment performed with a membrane-less model at 37 degrees C showed that the release of antithrombotic activity of rHV2 from PF127 gel followed zero-order kinetics and correlated well with the weight percentage of PF127 dissolved, indicating a dissolution-controlled release mechanism. The in vivo result obtained after subcutaneous injection of rHV2-loaded PF127 gel in normal rats demonstrated that PF127 gel improved the bioavailability, prolonged the antithrombotic effect of rHV2, and induced detectable plasma rHV2 concentration for a longer time in comparison with rHV2 aqueous solution. Differential scanning calorimetry, dynamic light scattering and Fourier transform infrared spectroscopy provided evidence of the interaction between PF127 and rHV2, but such interaction was unlikely to interfere the feasibility of this drug delivery system. Our current in vitro and in vivo study suggested that PF127 gel may be useful as an injectable delivery vehicle for peptides and proteins with short half-lives to prolong their therapeutic effect, increase their bioavailability and improve the clinic outcome.     

Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles.

Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F127 block copolymers (PEO-PPO-PEO) to obtain amphiphilic PLA-F127-PLA block copolymers. The block composition and structure of PLA-F127-PLA block copolymers were studied by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetric (DSC) and wide angle X-ray diffraction (WXRD) techniques. Data from DSC and WXRD measurements indicated that Tg and Tm of PLA blocks in PLA-F127-PLA block polymers are lower than those of PLA homopolymer. Furthermore, Tm and crystallinity of PLA blocks decrease with decreasing PLA block length in PLA-F127-PLA block copolymers. The release behaviors of both hydrophobic 9-(methylaminomethyl)anthracene (MAMA) and hydrophilic procaine hydrochloride (PrHy) model drugs from PLA-F127-PLA nanoparticles with vesicular structure in PBS solution at 37 degrees C were examined by UV spectroscopy. The release kinetics of both MAMA and PrHy model drugs from PLA-F127-PLA nanoparticles exhibit burst release characteristics, which are believed to be controlled by concentration gradient resulting from the slow hydrolytic degradation of PLA segments.     

Experimental investigation and mathematical modeling of Pluronic F127 gel dissolution: drug release in stirred systems.

We have examined the dissolution of Pluronic F127 gels in a USP dissolution apparatus under stirred conditions, and simultaneously monitored the release of model drugs from these gels. The drugs selected were propranolol HCl, metronidazole and cephalexin. Our results show that drug release is zero-order and is controlled by the dissolution of the gel for all the drugs, under various conditions of temperature, F127 concentration, drug concentration, and for stirring speeds between 20 and 80 rpm. The addition of inorganic salts has no significant effect on dissolution rate or drug release. Increasing F127 concentration in the gel decreases gel dissolution and drug release rates. We have developed a predictive mathematical model based on the assumption that uptake of water into the gel and subsequent disentanglement of F127 micelles control gel dissolution. There is good agreement between experimental results and model predictions for stirring speeds above 20 rpm. As stirring speed is decreased to 20 rpm and below, there are discrepancies between actual and predicted values, presumably due to a significant diffusion component that contributes to drug release.     

Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic block copolymers.

Micelles formed by Pluronic block copolymers (PBC) have been studied in multiple applications as drug delivery systems. Hydrophobic PBC form lamellar aggregates with a higher solubilization capacity than spherical micelles formed by hydrophilic PBC. However, they also have a larger size and low stability. To overcome these limitations, binary mixtures from hydrophobic PBC (L121, L101, L81, and L61) and hydrophilic PBC (F127, P105, F87, P85, and F68) were prepared. In most cases, PBC mixtures were not stable, revealing formation of large aggregates and phase separation within 1-2 day(s). However, stable aqueous dispersions of the particles were obtained upon (1). sonication of the PBC mixtures for 1 or 2 min or (2). heating at 70 degrees C for 30 min. Among all combinations, L121/F127 mixtures (1:1% weight ratio) formed stable dispersions with a small particle size. The solubilizing capacity of this system was examined using a model water-insoluble dye, Sudan (III). Mixed L121/F127 aggregates exhibited approximately 10-fold higher solubilization capacity compared to that of F127 micelles. In conclusion, stable aqueous dispersions of nanoscale size were prepared from mixtures of hydrophobic and hydrophilic PBC by using the external input of energy. The prepared mixed aggregates can efficiently incorporate hydrophobic compounds.     

Temperature-responsive and degradable hyaluronic acid/Pluronic composite hydrogels for controlled release of human growth hormone

Temperature-sensitive hyaluronic acid (HA) hydrogels were synthesized by photopolymerization of vinyl group modified HA in combination with acrylate group end-capped poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) tri-block copolymer (Pluronic F127). The synthesized HA/Pluronic composite hydrogels gradually collapsed with increasing temperature over the range of 5–40 °C, suggesting that the Pluronic component formed self-associating micelles in the hydrogel structure. Upon prolonged incubation in a buffer medium, the micelles slowly degraded due to the hydrolytic scission of the ester linkage between the Pluronic and acrylate group. The mass erosion occurred much faster at 37 °C than at 13 °C, indicating that at the higher temperature, the ester linkage between the Pluronic and acrylate group might be more exposed to an aqueous environment and thus be more readily hydrolyzed due to Pluronic micellization. Incorporation of recombinant human growth hormone in the hydrogel resulted in a sustained release profile which followed a mass erosion pattern.     

Pluronic F127/聚乳酸纳米粒子的药物作用

背景:国内关于纳米粒子在水及磷酸盐缓冲液中稳定性的研究报道较少。目的:考察PluronicF127/聚乳酸纳米粒子在水及磷酸盐缓冲液中的稳定性及PluronicF127/聚乳酸聚合物作为药物载体的可行性。方法:采用透析法制备PluronicF127/聚乳酸纳米粒子,通过高效液相色谱研究该纳米粒子作为药物载体包埋紫杉醇及体外释放行为,同时采用MTT法考察该聚合物的细胞毒性。结果与结论:PluronicF127/聚乳酸纳米粒子在水中的稳定性优于磷酸盐缓冲液,其次,温度对于纳米粒子的稳定性影响较大,无论是磷酸盐缓冲液还是水中,37℃条件下粒径变化均较大,因此纳米粒子在低温下稳定性较好。包埋紫杉醇的PluronicF127/聚乳酸纳米粒子的释放曲线在前20h内呈现快速释放,此后表现为缓慢释放,约有20%的紫杉醇释放出来,MTT测试结果表明PluronicF127/聚乳酸嵌段共聚物具有很好的生物相容性。综合以上结果表明,PluronicF127/聚乳酸适合用作药物载体。     

应用液态及凝胶态生物载体材料负载同种异体软骨细胞修复全厚关节软骨缺损

背景:应用固态载体作为细胞支架,修复关节软骨缺损,已有成功经验。尝试将液态载体或凝胶态载体材料复合细胞后注入动物体内,观察该方法的可行性。目的:探讨液态载体或凝胶态载体材料氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2负载同种异体软骨细胞修复全厚关节软骨的可行性。设计:对照实验。单位:威海市立医院骨科,山东省创伤骨科研究所。材料:实验于2001-11/2003-09在山东省创伤骨科研究所实验室进行。健康成年新西兰大白兔36只,体质量2.5～4.5kg,雌雄不限。编号后根据缺损处注入物质的成分随机数字法分成4组,即氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2软骨细胞组、氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2组、氧化聚乙烯和氧化聚丙烯复合物软骨细胞组、空白对照组,每组9只。方法:36只大白兔分组后造关节软骨缺损模型,取同种新西兰大白兔关节软骨细胞,体外培养扩增后与20%氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2混合,移植到缺损处进行修复。各移植组缺损处分别注入氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2负载软骨细胞、氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2、氧化聚乙烯和氧化聚丙烯复合物软骨细胞组。空白对照组:缺损处不做任何处理。移植后4,8,12周对缺损的修复情况进行大体、光镜组织学评估和电镜观察。据Wakitani评分标准,采用盲法对修复质量作出评价。主要观察指标:①软骨缺损修复程度。②软骨细胞的性质形态,基质中胶原性质、数量及排列方式。结果:①移植的氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2负载软骨细胞中的软骨细胞能很好地生长,4周时,缺损区完全填充。8,12周再生组织与周围正常软骨组织外观相似,界限模糊。组织学检查:形成透明软骨,缺损处被修复。②电镜下:8,12周,修复组织中可见多数成熟的透明软骨细胞及其周围排列不规则的、纤细的、均匀的和无周期性的Ⅱ型胶原。空白对照组仅见纤维修复,再生组织缺乏弹性,表面粗糙,不规则。③修复质量评分:氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2负载软骨细胞组和各组相比在各个时期差异均存在显著性,氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2组和氧化聚乙烯和氧化聚丙烯复合物软骨细胞组与对照组相比在各个时期差异均存在显著性[4周:(3.93±1.91),(4.56±1.07),(4.78±1.09),(8.44±1.13)分;8周:(2.80±1.45),(3.24±1.00),(3.33±1.00),(8.44±1.13)分;12周:(2.22±1.10),(3.01±0.69),(3.00±0.71),(9.00±0.87)分,P<0.001],但两组之间在各个时期无显著的差异(P>0.05)。结论:氧化聚乙烯和氧化聚丙烯复合物结合重组人骨形态蛋白2负载同种异体软骨细胞移植能以透明软骨的方式成功修复兔膝股骨髁软骨缺损,并优于单纯的氧化聚乙烯和氧化聚丙烯复合物负载重组人骨形态蛋白2或单纯的氧化聚乙烯和氧化聚丙烯复合物软骨细胞的移植。     

Preparation and properties of a stable intravenous lorazepam emulsion

Lorazepam is normally administered as a solution in organic solvents such as propylene glycol. This type of formulation is undesirable. This study describes the development of a parenteral emulsion formulation for lorazepam. The stability of lorazepam in the emulsion was examined. Ten per cent corn oil emulsions stabilized with egg lecithin, Pluronic F68 and Pluronic F88 were used. The incorporation of lorazepam does not appear to destabilize the emulsion, and lorazepam itself appears to be stable for at least 1 year in this liquid formulation.
Haemolysis caused by emulsion formulations containing lorazepam and different emulsifiers was evaluated using human and rabbit blood to assess their safety as parenteral drug carriers. The results show that the emulsions did not have any significant haemolytic activity whereas organic solvents and solutions of lorazepam in organic solvents caused substantial haemolysis.     

A green approach to prepare hierarchical porous carbon nanofibers from coal for high-performance supercapacitors

A green method is designed to obtain hierarchical porous carbon nanofibers from coal. In the work, deionized water, coal, polyvinyl alcohol and Pluronic F127 are used as the aqueous solution, carbon source, spinning assistant and soft template for spinning, respectively. As electrode materials for supercapacitors, the obtained hierarchical porous carbon nanofibers exhibit a high specific capacitance of 265.2 F g⁻¹ at 1.0 A g⁻¹ in 6 M KOH, a good rate performance with a capacitance of 220.3 F g⁻¹ at 20.0 A g⁻¹ with the retention of 83.1% and a superior cycle stability without capacitance loss after 20 000 charge/discharge cycles at 10.0 A g⁻¹. Compared with the carbon nanofibers constructed without Pluronic F127, the enhanced electrochemical performance of the sample benefits from a larger contact surface area and the mesoporous structure formed by decomposition of Pluronic F127 and good structural stability. This work not only provides a green route for high-value utilization of coal in energy storage, but also paves a new way to make hierarchical porous carbon nanofibers from coal for supercapacitor electrodes with high specific capacitance and long cycle life.

A green method is designed to obtain hierarchical porous carbon nanofibers from coal for supercapacitor electrodes with high specific capacitance and long cycle life.     

Gene expression control by temperature with thermo-responsive polymeric gene carriers.

A thermo-responsive copolymer, poly(N-isopropylacrylamide (IPAAm)-co-2-(dimethylamino)ethyl methacrylate (DMAEMA)-co-butylmethacrylate (BMA)), was synthesized and its in vitro gene transfection efficiency at different incubation temperatures was evaluated. A copolymer containing 8 mol% DMAEMA and 11 mol% BMA (P(IP-8DA-11BM)) had a lower critical solution temperature (LCST) at 21 degrees C, therefore the copolymer was insoluble above 21 degrees C and soluble below 21 degrees C. The LCST of P(IP-8DA-11BM) solution was not affected by the presence of salmon DNA. This copolymer was complexed with plasmid DNA, and the stability of the complex was analyzed by gel electrophoresis. DNA was completely retained in the complex, which was observed in the gel loading slot at 37 degrees C. At 20 degrees C, DNA was found to be partially dissociated from the complex by the appearance of the same band as DNA in the control experiment. These results clearly show that complex formation/dissociation was modulated by temperature alteration. The transfection efficiency of polymer-plasmid complexes was evaluated in COS-1 cells using pCMV-lacZ plasmid, encoding for beta-galactosidase as a reporter gene. The transfection efficiency of PDMAEMA homopolymer incubated at 37 degrees C for 48 h was greater than that incubated at 20 degrees C for 3 h and 37 degrees C for 45 h. In contrast, the transfection efficiency of P(IP-8DA-11BM) incubated at 20 degrees C for 3 h and 37 degrees C for 45 h was much higher than that incubated at 37 degrees C for 48 h. Such an increased transfection efficiency on lowering the temperature is considered to be due to appropriate formation/dissociation control of P(IP-8DA-11BM)-DNA complexes.     

Dual responsive oligo(lysine)-modified Pluronic F127 hydrogels for drug release of 5-fluorouracil

Peptide-containing hydrogels have become a research hotspot due to their unique secondary structure and biocompatibility. Herein, we used amino-terminated F127 as a macroinitiator to initiate the ring-opening polymerization of l-lysine(z)-NCA, and the obtained oligo(lysine)-modified F127 (FL) had degrees of polymerization of lysine of 2, 5, and 8. The results showed that the FL hydrogels had reversible temperature-dependent sol–gel transitions, and the introduction of lysine increased the critical gel temperature. In the dilute solution of FL, the micelle size increased and aggregated as the pH increased; the micelle grew into a rod-like shape under alkaline conditions. Scanning electron micrographs showed that the interior of the FL hydrogel had a more complete porous structure. The FL-2 hydrogel loaded with 5-fluorouracil exhibited an approximately linear release trend within 12 h and has good biocompatibility. Therefore, FL hydrogels have potential applications in the field of biomedicine.

Oligo(lysine)-F127 hydrogels have a temperature-responsive sol–gel transition and pH-responsive micelle morphology.     

Porcine feasibility and safety study of a new paclitaxel-eluting biliary stent with a Pluronic-containing membrane

Background and study aim: Metal stents for malignant biliary obstruction are susceptible to occlusion by tumor ingrowth or overgrowth. Therefore, we previously reported our use of a metal stent covered with a paclitaxel-incorporated membrane giving an antitumor effect to prevent occlusion from tumor ingrowth. We have also developed a new generation of paclitaxel-eluting biliary stent using a membrane containing Pluronic F-127 for effective drug delivery. The aim of this study was to investigate the safety and efficacy of drug delivery for this newly developed stent in the biliary tract. Methods: Metal stents were coated with paclitaxel and various concentrations of Pluronic F-127 in phosphate-buffered saline solution. Stents containing varying concentrations were placed in the bile ducts of eight pigs divided as follows: group I, 0 % Pluronic + 0 % paclitaxel; group II, 0 % Pluronic + 10 % paclitaxel; group III, 10 % Pluronic + 10 % paclitaxel; group IV, 20 % Pluronic + 10 % paclitaxel. The histology of the porcine bile duct and the amount of paclitaxel in the porcine serum were examined. The amount of paclitaxel released was also measured in vitro.Results: Histologic changes in the porcine biliary epithelium were acceptable in terms of safety, based on inflammatory cell infiltration and fibrotic reaction. No significant differences in histology were observed between the groups. In the porcine serum analysis, released paclitaxel was detected for 28 days with the 10 % Pluronic concentration (group III). However, released paclitaxel was observed for only 7 days in groups II and IV. In the in vitro experiments, long-lasting release of paclitaxel was also noted from the stent with 10 % Pluronic.Conclusions: The new paclitaxel-eluting stent with 10 % Pluronic F-127 is safe and provides enhanced local drug delivery.     

Effect of enzymatic degradation on the release kinetics of model drug from Pluronic F127/poly(lactic acid) nano-particles.

Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F127 block copolymer (PEO-PPO-PEO) to obtain amphiphilic PLA-F127-PLA block copolymers. The effect of enzymatic degradation on the release behaviors of hydrophobic model drug 9-(methylaminomethyl)anthracene (MAMA) from PLA-F127-PLA nano-particles with vesicular structure was studied by UV-Vis spectroscopy. It was observed that the release rate of MAMA from PLA-F127-PLA nano-particles with the enzymatic degradation varied with temperature due to the activity of the enzyme with temperature. However, the enzyme concentration has negligible effect on the release rates of MAMA.     

Effects of lipid segregation and lysolipid dissociation on drug release from thermosensitive liposomes.

Lysolipid-containing thermosensitive liposomes (LTSL) release their contents instantly when heated to temperatures close to their gel to liquid-crystalline phase transition temperature (TC). We have recently shown that during the melting transition these liposomes undergo major morphology changes, including the formation of open liposomes, bilayer discs, and pore-like defects. The hyperthermia-induced release of liposomal contents appears to depend on the presence and accumulation of membrane additives in grain boundaries, which enhance packing defects and, in the case of micelle-forming membrane additives, stabilize the bilayer rim of open liposome structures and transient membrane pores. In the present study, we used the fluorescent label 1-pyrenehexadecanoicacid (PHDA) and a radiolabelled lysolipid as markers for lysolipid membrane distribution and retention, respectively. PHDA dimer formation indicated local PHDA accumulation in cholesterol-free liposomes but not in cholesterol-containing liposomes. When LTSL were incubated at a temperature of 37 degrees C together with egg-phosphatidylcholine (EPC) multilamellar vesicles (MLVs) approximately 50% of the lysolipids transferred rapidly from LTSL to EPC MLVs. This transfer led to a significant reduction in the amount of carboxyfluorescein released from LTSL upon heating. Our results imply that poor retention of lysolipids in the LTSL membrane could also affect drug release characteristics of LTSL in vivo.