BACKGROUND & AIMS: :For folate receptor (FR) targeted anticancer therapy, novel folic acid (FA) conjugated cholesterol-modified glycol chitosan (FCHGC) micelles were synthesized and characterized by (1)H NMR, dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The degree of substitution was 1.4 FA groups and 7.7 cholesterol groups per 100 sugar residues of glycol chitosan. The critical aggregation concentration of FCHGC micelles in aqueous solution was 0.0169 mg/ml. The doxorubicin (DOX)-loaded FCHGC (DFCHGC) micelles were prepared by an emulsion/solvent evaporation method. The DFCHGC micelles were almost spherical in shape and their size increased from 282 to 320 nm with the DOX-loading content increasing from 4.53 to 11.4%. DOX released from DOX-loaded micelles displayed sustained release behavior. The targeted micelles encapsulated DOX showed significantly greater cytotoxicity against FR-positive HeLa cells than the nontargeted DOX-loaded micelles and free DOX. These results suggested that FCHGC micelles could be a potential carrier for targeted drug delivery.

背景与目标： 针对叶酸受体 (FR) 靶向抗癌治疗，合成了新型叶酸 (FA) 共轭胆固醇修饰的乙二醇壳聚糖 (FCHGC) 胶束，并通过 (1)H NMR，动态光散射，透射电子显微镜和荧光光谱对其进行了表征。取代度为1.4 FA组和7.7胆固醇组，每100糖残基乙二醇壳聚糖。FCHGC胶束在水溶液中的临界聚集浓度为0.0169 mg/ml。通过乳液/溶剂蒸发法制备了载有阿霉素 (DOX) 的FCHGC (DFCHGC) 胶束。DFCHGC胶束的形状几乎是球形的，并且它们的尺寸从282增加到320 nm，而DOX负载含量从4.53增加到11.4%。从载有DOX的胶束释放的DOX显示出持续释放的行为。与未靶向DOX负载的胶束和游离DOX相比，封装的DOX靶向胶束对FR阳性HeLa细胞显示出更大的细胞毒性。这些结果表明，FCHGC胶束可能是靶向药物递送的潜在载体。

BACKGROUND & AIMS: :An adenosine triphosphate (ATP)-fueled micellar system in the out-of-equilibrium state was constructed based on 4,5-diamino-1,3,5-triazine (DAT)-containing block copolymer. The block copolymer self-assembled into spherical micelles in equilibrium steady state at pH higher than its p Ka. The pendant DAT residues in protonated form acted as ATP catchers via hydrogen bonding and electrostatic interactions. Activated by ATP fuel, the polymeric micelles spontaneously disrupted into small aggregates of ATP/polymer hybrid complexes. The consumption of ATP energy via the enzymatic hydrolysis led to dissociation of the complexes and reversible formation of polymeric micelles. A transient self-assembly cycle, in which the assembly underwent autonomous division-fusion motion, was created using ATP fuel and enzyme; the switching of assembly structure was sustained by continuous supply of ATP fuel. This DAT-containing block copolymer have good biocompatibility, and drug-loaded micelles display ATP-responsive release behavior. It is expected that this ATP-fueled supramolecular assembly system will provide a functional platform for biomimic chemistry and therapeutic applications.

背景与目标： : 基于含4,5-二氨基-1,3，5-三嗪 (DAT) 的嵌段共聚物，构建了处于失衡状态的三磷酸腺苷 (ATP) 燃料胶束系统。嵌段共聚物在高于其p Ka的pH下以平衡稳态自组装成球形胶束。质子化形式的侧DAT残基通过氢键和静电相互作用充当ATP捕捉器。在ATP燃料的激活下，聚合物胶束自发地破裂成ATP/聚合物杂化复合物的小聚集体。通过酶水解消耗ATP能量导致复合物解离和聚合物胶束的可逆形成。使用ATP燃料和酶创建了一个瞬态自组装周期，其中组装经历了自主的分裂融合运动; 通过连续供应ATP燃料来维持组装结构的切换。这种含DAT的嵌段共聚物具有良好的生物相容性，载药胶束表现出ATP反应释放行为。预计这种以ATP为燃料的超分子组装系统将为生物化学和治疗应用提供功能平台。

BACKGROUND & AIMS: :Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile-AA) to form A/PAMs. A cell-targeting DNA aptamer with a 3' extension sequence (tail) complementary to the AA is annealed to the surface to form aptamer-displaying PAMs (Aptamer~A/PAMs). Aptamer~A/PAMs are small, anionic, stable nanoparticles capable of delivering a large mass percentage peptide amphiphile (PA) compared to targeting DNA components. Aptamer~A/PAMs are stable for over 4 h in the presence of biological fluids. Additionally, the aptamer retains its cell-targeting properties when annealed to the A/PAM, thus leading to enhanced delivery to a specifically-targeted B-cell leukemia cell line. This exciting modular technology can be readily used with a library of different targeting aptamers and PAs, capable of improving the bioavailability and potency of the peptide cargo.

背景与目标： 肽两亲胶束 (PAMs) 是用于递送各种治疗和预防肽的有吸引力的载体。然而，pam的一个关键限制是它们缺乏优先瞄准能力。在本文中，我们描述了我们的PAM系统的设计，该系统结合了DNA寡核苷酸两亲物 (antitail amphile-AA) 以形成a/PAMs。将具有与AA互补的3' 延伸序列 (tail) 的细胞靶向DNA适体退火到表面，以形成显示适体的PAMs (适体〜A/PAMs)。适体〜A/PAMs是小的，阴离子的，稳定的纳米颗粒，与靶向DNA成分相比，能够传递大质量百分比的肽两亲物 (PA)。适体〜A/PAMs在生物流体存在下稳定4小时以上。此外，当与A/PAM退火时，适体保留了其细胞靶向性，从而导致增强了对特异性靶向b细胞白血病细胞系的递送。这种令人兴奋的模块化技术可以很容易地与不同靶向适体和PAs的库一起使用，能够提高肽货物的生物利用度和效力。

BACKGROUND & AIMS: :Stimuli-responsive nanocarriers have demonstrated their potentials in optimizing chemotherapeutics and anticancer efficacy. In this study, a mixed micelle system (THSP) was prepared by combining reduction-sensitive hyaluronic acid-poly(lactide) (HA-ss-PLA) conjugates and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), with objective to achieve multiple functionalities of selective intracellular rapid release, active targeting capability and multidrug resistance reversal. The mixed micelle possessed desirable particle diameter of 124.32 nm and high entrapment efficiency at 87.97%. Importantly, the THSP mixed micelles demonstrated good stability in systemic circulation and rapidly released PTX in intracellular reductive environment. In vitro cellular uptake study and cytotoxicity assay indicated that the mixed micelles effectively increased drug accumulation in A549 cells and Taxol resistant A549/Taxol cells, and inhibited growth of tumor cells. In addition, the redox-responsive THSP micelles preferentially accumulated to the tumor site and improved anticancer drug activity in vivo, with a TIR of 69.08%. It was concluded that redox-sensitive mixed micelles THSP provided a potential vehicle for efficient anticancer drug delivery and enhancement in treating MDR tumor in the future.

背景与目标： : 刺激响应性纳米载体已证明其在优化化学疗法和抗癌功效方面的潜力。在这项研究中，通过结合还原敏感的透明质酸-聚丙交酯 (HA-ss-PLA) 缀合物和D-α-生育酚聚乙二醇丁二酸酯 (TPGS) 制备了混合胶束系统 (THSP)，目的是实现选择性细胞内快速释放的多功能，主动靶向能力和多药耐药逆转。混合胶束具有124.32  nm的理想粒径和87.97% 时的高截留效率。重要的是，THSP混合胶束在体循环中表现出良好的稳定性，并在细胞内还原环境中迅速释放PTX。体外细胞摄取研究和细胞毒性分析表明，混合胶束可有效增加A549细胞和紫杉醇耐药A549/紫杉醇细胞的药物积累，并抑制肿瘤细胞的生长。此外，氧化还原响应的THSP胶束优先积累到肿瘤部位并改善体内的抗癌药物活性，TIR为69.08%。结论是，氧化还原敏感的混合胶束THSP为将来有效的抗癌药物递送和增强MDR肿瘤的治疗提供了潜在的载体。

BACKGROUND & AIMS: :Targeted drug delivery systems (TDDS) have attracted wide attention for their reduced drug side effects and improved antitumor efficacy in comparison with traditional preparations. While targeting moieties in existing TDDS have principally focused on recognition of receptors on the surface of tumor cells, accumulation into tumor tissue only could be performed by enhanced permeability and retention effects and active transportation into tumor cells. Doxorubicin (DOX)-loaded sialic acid-dextran (Dex)-octadecanoic acid (OA) micelles (SA-Dex-OA/DOX) were designed for targeting hepatocellular carcinoma effectively. The synthesized conjugates could self-aggregate to form micelles with a critical micelle concentration of 27.6 μg·mL-1 and diameter of 54.53 ± 3.23 nm. SA-Dex-OA micelles incorporated with 4.36% DOX-loading content could prolong in vitro drug release to 96 h with 80% of final release. Cellular transportation studies revealed that SA-Dex-OA micelles mediated more efficient DOX delivery into Bel-7402 cells than those without SA modification. In vivo biodistribution testing demonstrated that SA-Dex-OA/ICG micelles showed 3.05-fold higher accumulation into Bel-7402 tumors. The recognition of overexpressed E-selectin in inflammatory tumor vascular endothelial cells led to a large accumulation of SA-Dex-OA/ICG micelles into tumor tissue, and the E-selectin upregulated on the surface of tumor cells contributed to active cellular transportation into tumor cells. Accordingly, SA-Dex-OA/DOX exhibited prior suppression of Bel-7402 tumor growth greater than that of Dex-OA/DOX micelles and free DOX (the tumor inhibition: 79.2% vs 61.0 and 51.3%). These results suggest that SA-functionalized micelles with dual targeting properties have high potential for liver cancer therapy.

背景与目标： : 与传统制剂相比，靶向药物递送系统 (TDDS) 因其降低的药物副作用和改善的抗肿瘤功效而受到广泛关注。尽管现有TDDS中的靶向部分主要集中在识别肿瘤细胞表面的受体上，但只能通过增强的渗透性和保留作用以及主动转运到肿瘤细胞中来完成向肿瘤组织的积累。设计了负载阿霉素 (DOX) 的唾液酸-葡聚糖 (Dex)-十八烷酸 (OA) 胶束 (SA-Dex-OA/DOX)，用于有效靶向肝细胞癌。合成的共轭物可以自聚成胶束，其临界胶束浓度为27.6 μ g·mL-1，直径为54.53 ± 3.23 nm。掺入4.36% DOX负载量的SA-Dex-OA胶束可将体外药物释放延长至96 h，最终释放80%。细胞运输研究表明，与没有SA修饰的相比，SA-Dex-OA胶束介导的DOX更有效地递送到Bel-7402细胞中。体内生物分布测试表明，SA-Dex-OA/ICG胶束在Bel-7402肿瘤中显示出3.05倍的高积累。在炎性肿瘤血管内皮细胞中过度表达的E-选择素的识别导致SA-Dex-OA/ICG胶束大量积聚到肿瘤组织中，并且在肿瘤细胞表面上调的E-选择素有助于细胞主动转运到肿瘤细胞中。因此，SA-Dex-OA/DOX表现出比Dex-OA/DOX胶束和游离DOX更大的先前对Bel-7402肿瘤生长的抑制 (肿瘤抑制: 79.2% 对61.0和51.3%)。这些结果表明，具有双重靶向特性的SA功能化胶束具有很高的肝癌治疗潜力。

BACKGROUND & AIMS: :Pluronics with different structural compositions and properties are used for several applications, including drug delivery systems. We developed a binary mixing system with two Pluronics, L121/P123, as a nano-sized drug delivery carrier. The lamellar-forming Pluronic L121 (0.1 wt%) was incorporated with Pluronic P123 to produce nano-sized dispersions (in case of 0.1 and 0.5 wt% P123) with high stability due to Pluronic P123 and high solubilization capacity due to Pluronic L121. The binary systems were spherical and less than 200-nm diameter, with high thermodynamic stability (at least 2 weeks) in aqueous solution. The CMC of the binary system was located in the middle of the CMC of each polymer. In particular, the solubilization capacity of the binary system (0.1/0.1 wt%) was higher than mono-systems of P123. The main advantage of binary systems is overcoming limitations of mono systems to allow tailored mixing of block copolymers with different physicochemical characteristics. These nano-sized systems may have potential as anticancer drug delivery systems with simple preparation method, high stability, and high loading capacity.

背景与目标： : 具有不同结构组成和性能的Pluronics用于多种应用，包括药物递送系统。我们开发了具有两个Pluronics L121/P123的二元混合系统，作为纳米级药物递送载体。将形成层状的Pluronic L121 (0.1重量 %) 与Pluronic P123掺入以产生纳米尺寸的分散体 (在0.1和0.5重量 % P123的情况下)，由于Pluronic P123具有高稳定性和Pluronic L121的高增溶能力。二元体系是球形的，直径小于200纳米，在水溶液中具有高热力学稳定性 (至少2周)。二元体系的CMC位于每种聚合物的CMC中间。特别地，二元体系的增溶能力 (0.1/0.1重量 %) 高于p123的单体系。二元体系的主要优点是克服了单体系的局限性，从而允许定制混合具有不同物理化学特性的嵌段共聚物。这些纳米系统可能具有制备方法简单，稳定性高和负载能力高的潜在抗癌药物递送系统。

BACKGROUND & AIMS: :Oxidative stress and inflammation are important mechanisms of cerebral ischemia reperfusion (IR) injury. Luteolin (Lu), one of the major active components in the classical Tibetan prescription, which has been used in the treatment of cardiovascular diseases since 700 BC, has potential for IR injury therapy. Its hydrophobicity has impeded its further applications. In this study, we first prepared Lu micelles (M-Lu) by self-assembling with an amphiphilic copolymer via the thin film hydration method to improve the dispersion of Lu in water. The obtained M-Lu was about 30 nm, with a narrow particle size distribution, and a 5% (w/w) of Lu. The bioavailability of the micelles was further evaluated in vitro and in vivo. Compared to free Lu, M-Lu had a better penetration efficiency, which enhanced its therapeutic effect in IR injury restoration. M-Lu further strengthened the protection of nerve cells through the nuclear factor-κ-gene binding κ (NF-κB) and mitogen-activated protein kinases (MAPK) pathways and inhibited the apoptosis of cells by adjusting the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in the case of oxidative stress damage. M-Lu induced stem cells to differentiate into neuron-like cells to promote the repair and regeneration of neurons. The results of in vivo pharmacodynamics of Lu on occlusion of the middle cerebral artery model further demonstrated that M-Lu better inhibited inflammation and the oxidative stress response by the down-regulation of the inflammatory cytokine, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the up-regulation of the activity of anti-oxidant kinase, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), which further ameliorated the degree of IR injury. The M-Lu could be a new strategy for IR injury therapy.

背景与目标： 氧化应激和炎症反应是脑缺血再灌注损伤的重要机制。木犀草素 (Lu) 是经典藏方的主要活性成分之一，自公元前700年以来一直用于治疗心血管疾病，具有潜在的IR损伤治疗潜力。它的疏水性阻碍了它的进一步应用。在这项研究中，我们首先通过薄膜水合方法与两亲共聚物自组装制备了Lu胶束 (M-Lu)，以改善Lu在水中的分散性。获得的M-Lu为约30 nm，具有窄的粒度分布，并且Lu的5% (w/w)。在体外和体内进一步评估了胶束的生物利用度。与游离Lu相比，M-Lu具有更好的穿透效率，增强了其在IR损伤修复中的治疗效果。M-Lu通过核因子-κ 基因结合 κ (NF-κ B) 和丝裂原活化蛋白激酶 (MAPK) 途径进一步加强对神经细胞的保护，并通过调节b细胞淋巴瘤-2 (Bcl-2) 和Bcl-2相关X蛋白的表达来抑制细胞凋亡 (Bax) 在氧化应激损伤的情况下。M-Lu诱导干细胞分化为神经元样细胞，促进神经元的修复和再生。Lu对大脑中动脉模型闭塞的体内药效学结果进一步表明，M-Lu通过下调炎性细胞因子，包括肿瘤坏死因子 (TNF)-α，白细胞介素 (IL)-1β 和IL-6，更好地抑制炎症和氧化应激反应，以及抗氧化激酶 (超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-px)) 活性的上调，进一步改善了IR的损伤程度。M-Lu可能是IR损伤治疗的新策略。

BACKGROUND & AIMS: :A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b-PEYM micelles assumed a stable core-shell structure in aqueous buffer at physiological pH with a low critical micelle concentration as determined by proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho ester side-chain at physiological pH was minimal yet much accelerated at mildly acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4 and was released at a much higher rate in response to slight acidification to pH 5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic profile, consisting of an initial fast phase of several hours followed by a sustained release period of several days. Dox loaded in the micelles was rapidly taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome and subsequently in the nucleus in a few hours, in contrast to the very low uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox-loaded micelles was determined by the MTT assay and compared with that of the free Dox. While the empty micelles themselves were not toxic, the IC(50) values of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times (by 48h) lower than the free drug. The much enhanced potency in killing the multi-drug-resistant human glioma cells by Dox loaded in the micelles could be attributed to high intracellular drug concentration and the subsequent pH-triggered drug release. These results establish the PEG-b-PEYM block copolymer with acid-labile ortho ester side-chains as a novel and effective pH-responsive nano-carrier for enhancing the delivery of drugs to cancer cells.

背景与目标： 合成并表征了一种新型的嵌段共聚物胶束，用于pH触发递送水溶性差的抗癌药物。胶束是通过两亲性二嵌段共聚物的自组装形成的，该两亲性二嵌段共聚物由亲水性聚 (乙二醇) (PEG) 嵌段和带有酸不稳定的邻酯侧链的疏水性聚甲基丙烯酸酯嵌段 (PEYM) 组成。通过PEG大分子引发剂通过原子转移自由基聚合 (ATRP) 合成二嵌段共聚物，以获得明确定义的聚合物链长。PEG-b-PEYM胶束在生理pH下的水性缓冲液中具有稳定的核壳结构，其临界胶束浓度较低，如质子NMR和pyr荧光光谱法测定。在生理pH下，原酯侧链的水解最小，但在轻度酸性pH下却大大加速。阿霉素 (Dox) 成功地在pH 7.4下加载到胶束中，并响应于轻微酸化至ph5以高得多的速率释放。有趣的是，在pH 5下Dox的释放显然遵循双相曲线，包括几个小时的初始快速阶段，然后是几天的持续释放期。在体外，人类神经胶质瘤 (T98G) 细胞迅速吸收了胶束中的Dox，并在溶酶体中积累，随后在几个小时内在细胞核中积累，而在相同剂量下游离药物的摄取非常低。通过MTT测定法确定了Dox负载的胶束的剂量依赖性细胞毒性，并将其与游离Dox的剂量依赖性细胞毒性进行了比较。虽然空胶束本身无毒，但载有Dox的胶束的IC(50) 值比游离药物低约十倍 (24小时) 和三倍 (48小时)。通过胶束中装载的Dox杀死多药耐药的人神经胶质瘤细胞的效力大大增强，这可能归因于高细胞内药物浓度和随后的pH触发的药物释放。这些结果建立了具有酸不稳定的邻酯侧链的PEG-b-PEYM嵌段共聚物，作为一种新型有效的pH响应纳米载体，可增强药物向癌细胞的递送。

BACKGROUND & AIMS: :We have investigated the responsiveness of micelle and bilayer surfaces to changes in bulk pH through titrations, and to changes in lipid packing through the application of high hydrostatic pressure using two fluorescent, pH-sensitive surface probes. In micelles, the surface is very sensitive to bulk pH while in phosphatidylcholine and phosphatidic acid bilayers the surface charge changed little through a large pH region. Application of pressure on micelles causes proton dissociation due to the volume reduction achieved from the contraction of water around the charges (electrostriction). However, in bilayers, the effect of electrostriction is greatly reduced, most likely due to the energy needed to expand and hydrate the surface. The sign and amount of change in dissociation the probe undergoes with pressure depend on the initial degree of probe dissociation, which is in turn dependent on the particular surface rather than the charge of the lipid head groups comprising the bilayer. This finding may limit the use of fluorescent probes to determine the exact surface potential. By assuming the change in delta V for proton dissociation from the probe is constant for a given pH, we can calculate the changes in local pH that occur under pressure relative to a neutral or uncharged system. In doing so, we find that the local pH around the probe in bilayers changes very little (approximately 0.1 pH unit or less) in the first 2000 bars. Also, if pressure data are coupled with titration curves, we can determine the change that the bulk pH must undergo to produce the observed change in dissociation seen under pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 我们使用两种荧光，pH敏感的表面探针研究了胶束和双层表面对滴定的整体pH变化以及通过施加高静水压力对脂质堆积变化的响应。在胶束中，表面对整体pH非常敏感，而在磷脂酰胆碱和磷脂酸双层中，表面电荷在较大的pH区域中变化很小。在胶束上施加压力会导致质子解离，这是由于电荷周围的水收缩 (电致伸缩) 引起的体积减小所致。但是，在双层中，电致伸缩的效果大大降低，这很可能是由于膨胀和水合表面所需的能量所致。探针随压力而发生的解离变化的符号和量取决于探针解离的初始程度，而初始程度又取决于特定表面而不是包含双层的脂质头基团的电荷。这一发现可能会限制使用荧光探针来确定确切的表面电势。通过假设质子解离探针的 Δ V变化对于给定的pH是恒定的，我们可以计算出相对于中性或不带电系统在压力下发生的局部pH变化。在这样做时，我们发现在前2000条中双层中探针周围的局部pH变化很小 (大约0.1 pH单位或更小)。此外，如果压力数据与滴定曲线相结合，我们可以确定主体pH必须经历的变化，以产生在压力下观察到的离解变化。(摘要截断为250字)

BACKGROUND & AIMS: :Biodegradable galactosylated methoxy poly(ethylene glycol)/poly(l-lactide-co-β-malic acid) (Gal-PEG-b-PLMA) block copolymer micelles were successfully prepared by a solvent diffusion method, and could efficiently encapsulate doxorubicin. The Gal-PEG-b-PLMA micelles before and after doxorubicin loading were characterized by size, morphology, in vitro drug release, and in vitro cytotoxicity in HepG2 cells. Transmission electron microscopy and dynamic light scattering results showed that the empty and doxorubicin-loaded micelles were approximately spherical in shape and had mean sizes of about 72 nm and 85 nm, respectively. In vitro release behavior of doxorubicin from the micelles was pH-dependent, with obviously faster release rates at mildly acidic pH 4.5 and 5.5 compared with physiologic pH 7.4. Methylthiazoletetrazolium assay and flow cytometric analysis indicated that the doxorubicin-loaded galactosylated micelles exhibited a greater growth-inhibitory effect on HepG2 cells than the nongalactosylated doxorubicin-loaded micelles, and induced S phase cell cycle arrest. Confocal laser scanning microscope observations revealed that the galactosylated micelles could be efficiently internalized by HepG2 cells through receptor-mediated endocytosis. The results suggest that Gal-PEG-b-PLMA copolymer micelles are a promising carrier system for targeted drug delivery in cancer therapy.

背景与目标： 通过溶剂扩散法成功制备了可生物降解的半乳糖基甲氧基聚 (乙二醇)/聚 (l-丙交酯-共-β-苹果酸) (Gal-PEG-b-PLMA) 嵌段共聚物胶束，可以有效地包封阿霉素。在装载阿霉素之前和之后的Gal-PEG-b-PLMA胶束的特征在于其大小，形态，体外药物释放和HepG2细胞的体外细胞毒性。透射电子显微镜和动态光散射结果表明，空胶束和阿霉素胶束的形状近似球形，平均尺寸分别约为72 nm和85 nm。阿霉素从胶束中的体外释放行为是pH依赖性的，与生理pH 7.4相比，在轻度酸性pH 4.5和5.5下释放速率明显更快。甲基噻唑啉测定和流式细胞仪分析表明，负载阿霉素的半乳糖基化胶束对HepG2细胞的生长抑制作用大于非半乳糖基化阿霉素的胶束，并诱导S期细胞周期停滞。共聚焦激光扫描显微镜观察表明，半乳糖基化胶束可以通过受体介导的内吞作用被HepG2细胞有效内化。结果表明，Gal-PEG-b-PLMA共聚物胶束是用于癌症治疗中靶向药物递送的有前途的载体系统。

BACKGROUND & AIMS: :Novel amphiphilic methoxy-poly(ethylene glycol)-poly(hexyl-substituted lactides) block copolymers were synthesized by ring-opening polymerization (ROP) of mono and dihexyl-substituted lactide (mHLA and diHLA) in bulk at 100 degrees C in the presence of tin(II) 2-ethylhexanoate (Sn(Oct)(2)) as catalyst and methoxy-poly(ethylene glycol) (MPEG) as initiator. MPEG-PmHLA and MPEG-PdiHLA copolymers of predictable molecular weights and narrow polydispersities were obtained, as shown by (1)H NMR and GPC. DSC experiments showed that the MPEG-PHLA block-copolymer presents a bulk microstructure containing MPEG domains segregated from the PHLA domains. Micelles were successfully prepared from these block copolymers, with sizes ranging from 30 to 80 nm. The critical micellar concentration (CMC) was found to decrease with the increasing number of hexyl groups on the polyester block (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) for copolymers of the same composition and molecular weight. The hydrophobicity of the micelle core in dependence of the number of hexyl groups along the PLA chain was evidenced by absorbance experiments with the incorporation of the dye Nile Red. These novel amphiphilic copolymers are interesting for micellar drug delivery and especially in regard to optimized hydrophobic drug loadings, as it was shown for griseofulvin as a model drug.

背景与目标： : 新的两亲性甲氧基-聚 (乙二醇)-聚 (己基取代的丙交酯) 嵌段共聚物是通过单和二己基取代的丙交酯 (mHLA和diHLA) 在100 ℃ 下在2-乙基己酸锡 (Sn (10月) 存在下的开环聚合 (ROP) 合成的。)(2) 作为催化剂，甲氧基聚乙二醇 (MPEG) 作为引发剂。如 (1)H NMR和GPC所示，获得了具有可预测分子量和窄多分散性的MPEG-PmHLA和MPEG-PdiHLA共聚物。DSC实验表明，MPEG-PHLA嵌段共聚物呈现包含与PHLA域分离的MPEG域的整体微观结构。由这些嵌段共聚物成功制备了胶束，尺寸范围为30至80 nm。对于相同组成和分子量的共聚物，发现临界胶束浓度 (CMC) 随着聚酯嵌段上己基的数量 (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) 的增加而降低。通过掺入染料尼罗红的吸光度实验证明了胶束核心的疏水性取决于沿PLA链的己基的数量。这些新颖的两亲性共聚物对于胶束药物递送是有趣的，尤其是在优化的疏水性药物负载方面，正如灰黄霉素作为模型药物所显示的那样。

BACKGROUND & AIMS: :A novel procedure for the preparation of hydrophilic peptide-containing oily formulations involving the freeze-drying of water-in-oil emulsions (FWE) is described. A mixture of an aqueous phase containing insulin and oil phase containing phosphatidylcholine was emulsified to prepare water-in-oil emulsions, which were subsequently lyophilized. Upon addition of oil, the lyophilates formed a clear oily solution which was considered as an anhydrous reverse micelle (ARM) system since it contained no water but 20-nm insulin nanoparticles, as revealed by dynamic light scattering. The 20-nm insulin nanoparticles, existing in a crystal form, were also contained in the lyophilates, as proved by scanning electron microscopy, small angle X-ray scattering and differential scanning calorimetry analysis. The drug release from the oily formulation of SPC/insulin (10:1) was slow and less than 12% of the total insulin was released after 24h. A significant reduction in the plasma glucose level of fasting diabetic rats after oral administration of insulin-containing ARMs confirmed the bioactivity of the drug and the potential usefulness of phospholipid-based oily formulations. Both the ARMs and lyophilates were stable and could be stored at 4 degrees C for at least 6 months. Thus, this simple FWE procedure is suitable for the solubilization of hydrophilic peptides in oil to produce stable products for therapeutic applications.

背景与目标： : 描述了一种制备含亲水性肽的油性制剂的新方法，该方法涉及油包水乳液 (FWE) 的冷冻干燥。将含有胰岛素的水相和含有磷脂酰胆碱的油相的混合物乳化以制备油包水乳液，随后将其冻干。加入油后，冻干物形成透明的油状溶液，该溶液被认为是无水反胶束 (ARM) 系统，因为它不含水，但含有20 nm的胰岛素纳米颗粒，如动态光散射所示。通过扫描电子显微镜，小角度x射线散射和差示扫描量热法分析证明，以晶体形式存在的20nm胰岛素纳米颗粒也包含在冻干物中。从SPC/胰岛素 (10:1) 的油性制剂中释放药物缓慢，并且在24小时后释放少于总胰岛素的12%。口服含胰岛素的手臂后，空腹糖尿病大鼠的血浆葡萄糖水平显着降低，证实了该药物的生物活性以及基于磷脂的油性制剂的潜在用途。臂和冻干物都是稳定的，可以在4 ℃ 下储存至少6个月。因此，这种简单的FWE程序适用于油中的亲水性肽的溶解，以生产用于治疗应用的稳定产品。

BACKGROUND & AIMS: :Concentration-dependent self-quenching of the fluorescent phospholipid N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine (N-NBD-PE) was used to measure the rate of N-NBD-PE transfer between phosphatidylcholine-bile salt mixed micelles. In a previous study using the same technique, the rate of N-NBD-PE transfer between phosphatidylcholine-taurocholate mixed micelles was found to be several orders of magnitude faster than its transfer between phosphatidylcholine vesicles as a result of an increased rate of transfer through the water at low micelle concentrations and an increased rate of transfer during transient micelle collisions at higher micelle concentrations [Nichols, J. W. (1988) Biochemistry 27, 3925-3931]. In this study we have determined the influence of bile salt structure, incorporation of cholesterol, and temperature on the rate and mechanism of phospholipid transfer between mixed micelles. We found that both transfer pathways were a common property of mixed micelles prepared from a series of different bile salts and that the rates of transfer by both pathways increased as a function of the degree of bile salt hydrophobicity. Cholesterol incorporation into phosphatidylcholine-taurocholate mixed micelles displaced taurocholate from the micelles and resulted in an increased rate of transfer through the water and a decreased rate of transfer during micelle collisions. The temperature dependence of the transfer rates was used to calculate the activation free energy, enthalpy, and entropy for both mechanisms. The activation enthalpy was the major barrier to transfer by both mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 荧光磷脂N-(7-硝基-2,1，3-苯并恶二唑-4-基) 磷脂酰乙醇胺 (N-NBD-PE) 的浓度依赖性自猝灭用于测量磷脂酰胆碱-胆盐混合胶束之间的N-NBD-PE转移速率。在先前使用相同技术的研究中，发现磷脂酰胆碱-牛磺胆酸盐混合胶束之间的N-NBD-PE转移速率比其磷脂酰胆碱囊泡之间的转移速率快几个数量级，这是由于在低胶束浓度下通过水的转移速率增加以及在较高胶束浓度下瞬时胶束碰撞过程中的转移速率增加 [·尼科尔斯，J. W. (1988) 生物化学27,3925-3931]。在这项研究中，我们确定了胆汁盐结构的影响，和温度对混合胶束之间磷脂转移速率和机制的影响。我们发现这两种转移途径是由一系列不同胆汁盐制备的混合胶束的共同性质，并且这两种途径的转移速率随胆盐疏水性程度的变化而增加。胆固醇掺入磷脂酰胆碱-牛磺胆酸盐混合胶束从胶束中取代牛磺胆酸盐，导致通过水的转移速率增加，胶束碰撞过程中转移速率降低。转移速率的温度依赖性用于计算活化自由能，两种机制的焓和熵。激活焓是两种机制转移的主要障碍。(摘要截断为250字)

BACKGROUND & AIMS: :A novel oriented immobilized lipase was derived from Yarrowia lipolytica lipase LIP2 covalently immobilized on functionalized Fe3O4 magnetic nanoparticles (MNPs) in reverse micelles system (RMS). The activity recovery reached 382% compared with 29% in aqueous phase, and further ran up to 1425% under optimum conditions. (3-Aminopropyl) triethoxysilane (APTES) coated Fe3O4 nanoparticles were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). A significant alteration in the secondary structure of the lipase in RMS with a 15.5% increase of α-helix content and a 12.5% decrease of β-sheet content was detected by circular dichroism (CD). The immobilized lipase was employed to enrich polyunsaturated fatty acids in fish oil, a 90% increase of DHA content was obtained after 12h, and after 20 cycles of successive usage, it still remained over 80% of relative hydrolysis degree, which shows a good recyclability.

背景与目标： : 一种新型的定向固定化脂肪酶是从共价固定在反向胶束系统 (RMS) 中官能化的Fe3O4磁性纳米颗粒 (MNPs) 上的lipolywia lipolytica脂肪酶LIP2衍生而来的。与水相中的29% 相比，活性回收率达到382%，并在最佳条件下进一步达到1425%。通过傅里叶变换红外 (ft-ir) 和x射线衍射 (XRD) 对 (3-氨基丙基) 三乙氧基硅烷 (APTES) 包覆的Fe3O4纳米颗粒进行了表征。通过圆二色性 (CD) 检测到，随着 α-螺旋含量的15.5% 增加和 β-折叠含量的12.5% 降低，RMS中脂肪酶的二级结构发生了显着变化。固定化脂肪酶用于丰富鱼油中的多不饱和脂肪酸，12h后DHA含量90% 增加，连续使用20个循环后，仍保持相对水解度80% 以上，显示出良好的可回收性。

BACKGROUND & AIMS: PURPOSE:Polymeric micelles have been used for solubilization of insoluble drugs and as carriers for drug delivery applications. Here we evaluated an application of the synthetic polymeric micelles in experiments designed to improve the handling and stability of membrane proteins targets. METHODS:Particle sizing by dynamic light scattering was performed in a Zeta Plus Photon Correlation Spectrometer at 532 nm. UGT1A1 activity has been measured in fluorescent assay using scopoletin as a substrate. COX-2 activity has been measured in a fluorescent assay using Amplex Red. Fluorescence Resonance Energy Transfer (FRET) was monitored using either 463 nm excitation wavelength (the emission range 500-600 nm) or 395 nm excitation wavelength (the emission range 500-600 nm). RESULTS:Incorporation of membrane proteins into PreserveX-QML polymeric micelles resulted in improved homogeneity and stability of the preparation and in reduced light scattering. Stabilization of the biological activity of micelle-incorporated membrane proteins, such as the human UGT1A1 and COX-2 both during extended incubations at room temperature and during multiple freeze/thaw cycles, has been achieved. CONCLUSION:PreserveX-QML polymeric micelles help to homogenize and disperse membrane proteins preparations and stabilize the biological activity of the proteins making it more suitable for pharmaceutical assays and applications.

背景与目标：