Effects of Polyethyleneglycol Chain Length and Phospholipid Acyl Chain Composition on the Interaction of Polyethyleneglycol-phospholipid Conjugates with Phospholipid: Implications in Liposomal Drug Delivery

Purpose. The purpose of this study was to investigate polyethyleneglycol(PEG)-phosphatidylethanolamine(PE) conjugate interaction with phospholipid bilayers, in an attempt to explain the dependence of liposome circulation time on formulation. Methods. Differential scanning calorimetry, electron microscopy, dynamic light scattering and NMR were the major methods used in the study. Results. Mixtures of PEG-phospholipid conjugates and phosphatidylcholine existed in three different physical states: a lamellar phase with components exhibiting some miscibility, a lamellar phase with components phase separated, and mixed micelles. Beyond 7 mol% of PEG(l,000–3,000)-dipalmitoyl phosphatidylethanolamine (DPPE), and 11 mol% PEG(5,000)-DPPE in dipalmitoyl phosphatidylcholine (DPPC), a strong tendency towards mixed micelle formation was observed. All concentrations of PEG(12,000)-DPPE and PEG(5,000)-DPPE beyond 8 mol% formed phase separated lamellae with phosphatidylcholine. Decreasing the acyl chain length from C_16:0 to C_14:0 caused a decrease in tendency towards micelle formation and phase separation. These tendencies increased upon increasing acyl chain length to C_18:0. Phase separation was at least partly due to PEG chain-chain interaction. This was supported by an increased fraction of PEG chains exhibiting a fast NMR transverse relaxation in DPPC/PEG(5,000)-DPPE mixtures as compared to that in distearoyl phosphatidylcholine (DSPC)/PEG(5,000)-dioleoyl-PE (DOPE). Conclusions. These phenomena are discussed in relation to both bilayer and steric stabilization of liposomes, and the lack of prolonged circulation with certain formulations is discussed.     

Oral Controlled Release Technology for Peptides: Status and Future Prospects

In spite of significant efforts in academic and commercial laboratories, major breakthroughs in oral peptide and protein formulation have not been achieved. The major barriers to developing oral formulations for peptides and proteins include poor intrinsic permeability, lumenal and cellular enzymatic degradation, rapid clearance, and chemical and conformational stability. Pharmaceutical approaches to address these barriers, which have been successful with traditional, small, organic drug molecules, have not readily translated into effective peptide and protein formulations. The success achieved by Sandoz with cyclosporin formulations remains one clear example of what can be achieved, although it is likely that effective oral formulations for peptides and proteins will remain highly compound specific. Although the challenges are significant, the potential therapeutic benefit remains high, particularly with the increasing identification of potential peptide and protein drug candidates emerging from the biotechnology arena. Successful formulations will most likely require a systematic and careful merger of formulation and design delivery systems which maximize the potential for absorption across the epithelial cell layer.     

The use of locally-delivered chlorhexidine in the treatment of periodontitis. Clinical results*

Abstract. Since the advent of a nondegradable controlled local delivery of antibiotics in 1979, several second generation systems have been developed. Second generation systems have attempted to improve on the early system. Chlorhexidine has been used effectively for over 30 years as an antiseptic. In the early 1970s, chlorhexidine gluconate was incorporated at 0.2% into mouthrinses in Europe and in 1986 it was incorporated at 0.12%, in a mouthrinse in the United States. Since these mouthrinses were effective in reducing the supragingival flora, had a high safety margin, and had no reported bacterial resistance, chlorhexidine offered a therapeutic advantage for a local delivery system. This system was developed and studied. This report will discuss this new biodegradable system containing chlorhexidine gluconate as the active agent (PerioChip^®). Parmacokinetics of the system and a review of the multicenter studies in Europe and the United States are discussed. In these randomized clinical trials the chlorhexidine chip has been shown to enhance the effects of scaling and root planing. Chlorhexidine chip in conjunction with scaling and root planing, when compared to scaling and root planing alone, has shown significant improvement in probing pocket depth reduction, probing attachment level and bleeding on probing. This delivery system, in combination with scaling and root planing, has also resulted in significantly more probing depth reductions of 2 mm or more. The system is safe and efficacious. Placement of the chip is usually done in less than 1 min, it requires no retention system, biodegrades, and does not require a follow-up dental appointment.     

Favorable effects of epidural analgesia on hemodynamics,oxygenation and metabolic variables in the immediate post-anesthetic period

Fourteen adult patients undergoing elective major abdominal surgery were divided into two groups. One group received epidural and general anesthesia (epidural group), and 20 ml of 0.125% bupivacaine and 2 mg of morphine were administered epidurally about 30 min before the end of the operation for post-anesthetic analgesia. The other group (control group) received general anesthesia alone with nitrous oxide, oxygen and enfiurane. Flow-directed pulmonary arterial and radial arterial catheters were inserted preoperatively, and hemodynamic, respiratory, neuroendocrine and metabolic variables were measured serially. The data were compared during anesthesia and the immediate post-anesthetic recovery period. In the control group, the plasma epinephrine level in the post-anesthetic recovery period increased about four times over the anesthetic period. Oxygen consumption was increased and mixed venous oxygen saturation was decreased significantly. There was a close linear correlation between oxygen consumption (Y) and plasma epinephrine (X) level: Y = 285.7X + 90.5 (P < 0.01, r = 0.72). On the other hand, plasma epinephrine, oxygen consumption and mixed venous oxygen saturation did not change significantly in the epidural group in the post-anesthetic recovery period. There was also a close linear correlation between oxygen consumption (Y) and oxygen delivery (X): Y = 0.22X -32.0 (P < 0.01, r = 0.89). We conclude that the surgical stress and anesthetic reversal may seriously influence neuroendocrine responses and subsequently increase plasma epinephrine. Tissue oxygenation and metabolic imbalance may occur due to the rapid increase of epinephrine in the postanesthetic recovery period. Epidural analgesia at this period may play a more important role and have a more favorable effect on the tissue metabolism.     

硬膜外镇痛联合应用乙酰氨基酚在剖宫产术后的镇痛效果

目的：比较对乙酰氨基酚联合自控硬膜外镇痛的多模式术后镇痛与单纯自控硬膜外镇痛用于剖宫产产妇术后镇痛效果。方法：200名行剖宫产的产妇随机分为实验组（S组）和对照组（C组）,S组产妇在术前15min静脉注射对乙酰氨基酚1g,C组产妇在术前15min静脉注射安慰剂（生理盐水）。两组产妇均采用腰硬联合麻醉方案,缝合切口时启动自控硬膜外镇痛泵。术前、术后即刻、术后1天、术后2天观察疼痛强度和血清IL-6、IL -10水平;记录新生儿出生Apgar评分、术后阿片类药物使用量及术后不良反应、产妇满意度和对母乳喂养的影响程度。结果：术后1天疼痛评分S组显著低于C组。术后即刻、术后1天S组IL-6表达水平低于C组,而该时点S组IL-10表达水平高于C组（P＜0.05）。两组间不良反应、新生儿出生Apgar评分、产妇满意度和母乳喂养情况无统计学差异（P＞0.05）。结论：剖宫产术前静脉注射对乙酰氨基酚联合自控硬膜外镇痛比单独应用自控硬膜外镇痛能够为产妇提供更好的术后疼痛管理。     

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of -glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.     

骨内植入式药物缓释系统载体材料研究现状及进展

植入式药物缓释系统在治疗骨科感染、肿瘤等方面具有良好的作用。随着组织工程学的进展,研制了不同的材料作为骨内植入式药物缓释系统的载体,拟对骨内植入式药物缓释系统载体材料研究现况及进展进行综述。     

超声波介导的基因输送技术

近年来超声波介导的基因输送技术由于其相对安全性和操作上的简单得到关注。本文对超声波导致的声致穿孔的机制,空化核的作用——增强基因输送的效率,以及细胞和在体基因输送效率作了综述,讨论了超声波介导的基因输送效率的影响因素。此方法充满希望并且载药的空泡可以作为一种新型药物载体在超声作用下实现药物的靶向输送     

产妇抑郁对泌乳与产后流血的影响

目的：探讨产妇抑郁对泌乳与产后流血的影响。方法：对309例产妇采用自评抑郁量表评分，分成产后抑郁组和对照组，测评泌乳指标、产后流血的差异。结果：抑郁组产妇泌乳始动时间迟，产后24小时泌乳者仅13例；泌乳量少，产后72小时泌乳量多者仅13例；抑郁组产妇产后流血量多，与对照组相比差异有显著性。结论：产妇抑郁对泌乳与产后流血有不利影响，应加强对产妇进行心理健康指导。     

心理治疗在全程助产责任制中的应用

目的探村心理治疗封产科全程助产责任制分娩模式的影响。方法选择2002年3月至2004年9月在我院住院的初产妇1700例（均孕足月、单胎、无难产指征），随机分为治疗组和对照组两组，比较两组分娩方式、产程时间、产后出血。结果第一产程及总产程均短于对照组（P〈0．05），两组剖宫产率、阴道助产率、产后出血率比较均有显著差异（P〈0．05）。结论心理治疗应用于产科全程助产责任制，使产妇得到心理安慰和生理上的帮助，保障母婴健康，值得推广使用。