Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (T_m), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the T_m shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model.     

磷脂酰胆碱抗氧化效应及对遗传损伤的保护作用

磷脂酰胆碱５００ｍｇ／ｋｇ灌胃２０日可使Ｏ_３环境中的小鼠超氧化物歧化酶（ＳＯＤ）活性显著增强，血浆丙二醛（ＭＤＡ）含量及外周血正染红细胞（ＮＣＥ）微核率明显下降。结果提示：磷脂酰胆碱具有抗氧化作用及拮抗自由基造成遗传的损伤。进一步证实了自由基在微核形成中具有重要意义。     

Major phospholipids and phosphatidylcholine synthesis in adult Schistosoma mansoni

The major phospholipids present in the phospholipid extract of Schistosoma mansoni were phosphatidylcholine (28%), phosphatidylethanolamine (25%), phosphatidylserine (15%) and phosphatidylglycerol (8%). The synthesis of phosphatidylcholine in S. mansoni adults occurred by the choline to phosphatidylcholine or Kennedy pathway. Incorporation of CDPcholine and choline into the phosphatidylcholine of worm slices appeared linear over time with no demonstrable sex differences in choline incorporation. A slight difference in the incorporation of CDPcholine by separate sexes was evident. Methylation of phosphatidylethanolamine to phosphatidylcholine could not be demonstrated.     

Phospholipase-resistant phosphatidylcholine reduces intra-abdominal adhesions induced by bacterial peritonitis

The majority of intra-abdominal adhesions develop postoperatively or following peritonitis. We have previously shown thatl-phosphatidylcholine reduces postoperative peritoneal adhesions in rats. In the present study, we examined whether adhesion formation after bacterial peritonitis is also reduced byl-phosphatidylcholine or bydl-α-phosphatidylcholine, which is degraded only 50% by phospholipase A₂. Peritonitis was induced in the rat by caecal ligation and double puncture; cecotomy was performed 12, 15, or 18h later. Adhesions were assessed blindly by a scoring system 7 days after cecotomy. When cecotomy was scheduled for 18h after caecal ligation and puncture, the 7-day mortality was 90% (n=20). When cecotomy was performed at 12h, no mortality was seen; however, the adhesion score was low (2.3±0.7). When cecotomy was performed 15h after caecal ligation and puncture, the mortality was 25% and the adhesion score was 4.3±0.9. This figure was reduced significantly by intraperitoneal instillation ofl-phosphatidylcholine ordl-α-phosphatidylcholine for 3 subsequent days. However, the mortality increased byl-phosphatidylcholine (P<0.01), whereas mortality afterdl-α-phosphatidylcholine remained at 30%. We conclude that administration of bothl-phosphatidylcholine anddl-α-phosphatidylcholine decrease adhesion formation after bacterial peritonitis.     

Combined Effects of Phosphatidylcholine and Demineralized Bone Matrix on Bone Induction

The osteoinductivity of demineralized bone matrix (DBM) becomes significantly reduced if the specimens are further delipidated with chloroform-methanol. The addition of phosphatidylcholine (PC), a major constituent of the lipid fraction present in the calcification front during normal bone formation, can restore the biological activity. Active endochondral bone formation is observed in the DBM/PC implants placed in the anterior abdominal wall musculature or subcutaneously for 28 days. When PC is added to generate a putty containing 60% PC and 40% DBM, biochemical parameters associated with osteoinductivity are significantly enhanced. Biological responses evaluated histologically and by determination of alkaline phosphatase activity are in very good agreement. The DBM/PC putty has good handling properties, can be molded into different shapes, and does not wash away from the application site. An advantage of adding PC is that it not only enhances the handling properties, but also boosts the osteoinductivity of the preparation.     

An in vitro assessment and comparative effectiveness of silanized-glutaraldehyde functionalized titanium surfaces with phosphatidylcholine and type I collagen grafts

ObjectiveThis study aims to evaluate sequence-modified Ti surfaces functionalized with silanized glutaraldehyde and further grafted with the active biomolecules of phosphatidylcholine and type I collagen (COL I).MethodsThe properties of the functional surfaces were investigated by various surface analysis techniques and characterized their capability in osteogenic cell attachment, differentiation, and mineralization in vitro.ResultsThe Ti surfaces grafted with phosphatidylcholine and COL I effectively improved the hydrophilicity. In addition, an effect of COL I concentrations (higher than 2.5 μg/mL) do not stimulate subsequent alkaline phosphatase (ALP) activity during osteogenesis in vitro. However, the result is different in phosphatidylcholine, that is, as the concentration of phosphatidylcholine increased enhances subsequent osteogenetic properties. The Ti groups with bioactive molecules affected cell characteristics in vitro in contrast to the controlled Ti group. The proliferation and differentiation levels of osteoprogenetor cells were enhanced and ALP was strongly expressed in the groups grafted with phosphatidylcholine and COL I.SignificanceThis modification promotes progenitor bone cell adhesion, proliferation, and differentiation and thus drastically improves the success rate for implant modification by accelerating surface osseointegration.     

Different metabolic profiles of K1 serotype and non-serotype K1 and K2 Klebsiella pneumoniae isolates in oral infection mice model

K1 or K2 serotype Klebsiella pneumoniae isolate caused clinical pyogenic liver abscess (KLA) infection is prevalent in many areas. It has been identified that K1 or K2 serotype K. pneumoniae isolates caused KLA infection in mice by oral inoculation. In our study, K1 serotype K. pneumoniae isolate Kp1002 with hypermucoviscosity (HV)-positive phenotype caused KLA infection in C57BL/6 mice by oral inoculation. Simultaneously, non-serotype K1 and K2 isolate Kp1014 with HV-negative phenotype failed to cause KLA infection in the same manner. It seems that gastrointestinal tract translocation is the pathway by which K1 or K2 serotype K. pneumoniae caused KLA infection. Liquid chromatography-tandem mass spectrometry was used to further analyze metabolic profile changes in mice with KLA infection. Data showed that after Kp1002 or Kp1014 oral inoculation, serum Phosphatidylcholine (PC) and Lysophosphatidylcholine (LPC) levels significantly changed in mice. Some PC and LPC molecules showed changes both in the Kp1002 KLA group and the Kp1014 no-KLA group compared with the control group. The level of 18:1/18:2-PC significantly changed in the Kp1002 KLA group compared with the control group, but showed no change between the Kp1014 no-KLA group and the control group. The level of 18:1/18:2-PC might have been particularly affected by KLA infection caused by K1 serotype K. pneumoniae Kp1002. It may be a potential biomarker for KLA infection.     

胆宁片联合多烯磷脂酰胆碱胶囊治疗非酒精性脂肪肝的疗效观察

目的探讨胆宁片联合多烯磷脂酰胆碱胶囊治疗非酒精性脂肪肝的临床疗效。方法收集2015年4月—2016年4月在上海杨浦区五角场街道社区卫生服务中心进行治疗的非酒精性脂肪肝病患者88例,随机分为对照组(44例)和治疗组(44例)。对照组口服多烯磷脂酰胆碱胶囊,2粒/次,3次/d。治疗组在对照组的基础上口服胆宁片,5片/次,3次/d。两组患者均连续治疗6个月。评价两组患者临床疗效,同时比较两组治疗前后血脂水平和肝功能改变。结果治疗后,对照组和治疗组总有效率分别为81.82%、97.73%,两组总有效率比较差异有统计学意义(P0.05)。治疗后,两组患者三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)水平均显著降低,而高密度脂蛋白(HDL-C)则明显升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组患者上述血脂水平改善程度优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和γ-谷氨酰转移酶(γ-GT)水平均比同组治疗前显著降低,同组比较差异具有统计学意义(P0.05);且治疗组患者肝功能改善程度显著优于对照组,两组比较差异具有统计学意义(P0.05)。结论胆宁片联合多烯磷脂酰胆碱胶囊治疗非酒精性脂肪肝效果显著,可明显降低患者血脂水平,具有一定的临床推广应用价值。     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.     

强肝胶囊联合多烯磷脂酰胆碱胶囊治疗NAFLD的疗效和机制研究

目的研究强肝胶囊联合多烯磷脂酰胆碱胶囊治疗非酒精性脂肪肝的疗效和机制。方法2008年1月～2010年12月本院感染科就诊的150例非酒精性脂肪性肝病患者随机分为对照组和治疗组各75例。两组患者均进行饮食控制和体育锻炼。对照组患者服用多烯磷脂酰胆碱胶囊,治疗组患者服用多烯磷脂酰胆碱胶囊和强肝胶囊,两组疗程均为3个月。观察治疗前及3个月后两组患者的临床症状、肝功能参数、血脂水平的变化,并对血清肝纤维化指标、氧化应激指标进行检测。结果治疗组总有效率显著高于对照组（P〈0．01）。治疗后治疗组肝功能参数、血脂、血清肝纤维化指标和氧化应激指标与对照组比较差异有统计学意义（P〈0．01）。结论强肝胶囊联合多烯磷脂酰胆碱胶囊对非酒精性脂肪肝具有显著的治疗效果,其作用机制可能与降低血脂水平、抑制肝脏纤维化以及降低氧化应激反应等有关。