Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.     

Anionic long‐circulating liposomes for delivery of radioiodinated antisense oligonucleotides

Long‐circulating liposomes have been widely used to enhance efficacy of gene therapy. Antisense therapy might increase the efficacy of radiation or chemotherapy; therefore, we undertook to optimize the composition of the liposomal delivery vehicles. The radiolabeling efficiency, radiochemistry purity, and specific radioactivity of radioiodinated antisense oligonucleotides (ASON) were 71.66 ± 7.73, 98.33 ± 0.39%, 4.09 ± 0.11 MBq/nmol. Radioiodinated ASON remained stable in 0.01 M HEPES buffer and human serum even after incubation for 4 hours. Mean diameter of the anionic long‐circulating liposomes (ALCL) was 504 ± 31.76 nm with a polydispersity index (PDI) of 0.107 ± 0.008 before extrusion, 115 ± 8.5 nm with a PDI of 0.103 ± 0.002 after extrusion. The zeta potential of ALCL was ?29.23 ± 0.45 mV. ALCL prepared for this study provided 70.28 ± 1.84% encapsulation efficiency. Compared with other liposome formulations, the ALCL mediated enhanced cellular uptake (32.51 ± 1.44%) by MCF‐7 breast cancer cells (p<0.05). Practical applications: Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. LCL have become a commonly used carrier for gene therapy recently. ALCL are promising for the mediated radiation and antisense therapy for breast cancer which is the leading cause for women.     

Solubilization of phosphatidylcholine unilamellar liposomes caused by alkyl glucosides

Solubilizing alterations caused by a series of alkyl glucosides (alkyl chain lengths ranging from C₈ to C₁₂) in phosphatidylcholine (PC) unilamellar liposomes were investigated. Surfactant-to-phospholipid molar ratios (Re) and bilayer/aqueous phase partition coefficients (K) were determined by monitoring changes in static light scattering (SLS) of the system during solubilization. At the two interaction levels investigated (surfactant concentrations producing SLS values of 100 and 0% for each surfactant/PC system studied) the free surfactant concentration for each surfactant was always comparable to its critical micelle concentration (CMC). This indicates that liposome solubilization was mainly ruled by mixed micelle formation. A rise in CMC (or decrease in the surfactant alkyl chain length) resulted in an increase in the ability of these surfactants to saturate or solubilize PC liposomes and, inversely, in an abrupt decrease in their affinity with these bilayer structures. The overall balance of these opposite tendencies shows that the octyl glucoside had the highest ability to saturate and solubilize liposomes (lowest Re values), whereas the dodecyl glucoside exhibited the highest degree of partitioning into liposomes or affinity with bilayer structures (highest K values). From a practical viewpoint, the use of nonyl glucoside reduced approximately 2.5 times the concentration needed to saturate and solubilize 1.0 mM PC liposomes with respect to that needed using the conventional octyl glucoside.     

Efficient intraliposomal entrapment of hydrophilic platinum oligonuclear complexes

A simple method for intraliposomal entrapment of platinum complexes is presented, where hydrophilic platinum oligonuclear complexes, 1-methyluracil green (MeUG), uridine green (UdG) and uridine blue (UdB), are included inside liposomes and allowed to react with bilayer lipids. The liposomes prepared in this method exhibit higher entrapment efficiency and higher distribution to organs (liver, kidney, spleen, lung) and blood (but not B16 cancer cells) than those prepared from mononuclear Pt complexes [cis-diamminedichloroplatinum, cis-diammine-1,1′-dicarboxylatocyclobutaneplatinum, and cis-dichloro-cis-dihydroxy-trans-bis(isopropylamine)platinum)].     

Assembly properties of the aggregates resulting in the solubilization of phosphatidylcholine bilayers by sodium cholate

The interaction of sodium cholate with phosphatidylcholine liposomes was investigated. Permeability alterations were detected as a change in 5(6)-carboxyfluorescein (CF) released from the interior of vesicles and bilayer solubilization as a decrease in the static light-scattered by liposomes. Free surfactant concentration at subsolubilizing and solubilizing levels showed, respectively, values that were lower than and similar to the surfactant critical micelle concentration, and indicated that permeability alterations and solubilization were determined, respectively, by the action of surfactant monomer and by the formation of mixed micelles. A direct relationship was established in the initial steps [effective surfactant/lipid molar ratio (Re) lower than 0.07] between the growth of vesicles, the leakage of entrapped CF (fluidity of vesicles), and Re. These changes could be correlated with the increasing presence of surfactant molecules in the outer monolayer of vesicles and its saturation. The subsequent increase in Re led to a lower growth of vesicles in coexistence with a similar increase in the CF release. This behavior could be related to a increased rate of flipflop of the sodium cholate molecules, making the inner monolayer also available for the interaction with added surfactant. A direct dependence was also established in the initial solubilization steps (Re values up to 0.6) between the surfactant-phosphatidylcholine aggregate size, the static light-scattering of the system, and Re. In the Re interval 0.36–0.84 mixed vesicles and mixed micelles coexisted.     

Novel Formulations for Antimicrobial Peptides

Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.     

紫甘薯花青素脂质体制备工艺的优化

以大豆卵磷脂、胆固醇为膜材,采用逆相蒸发法制备紫甘薯花青素脂质体,以凝胶柱层析法测定脂质体中紫甘薯花青素的包封率,得出制备紫甘薯花青素脂质体的最优工艺条件为:胆固醇与大豆卵磷脂物质的量比为1∶2,紫甘薯花青素水溶液(0.250 mg·m L-1)与乙醚的体积比为1∶4,逆相蒸发时间为30min,上述条件制备的脂质体平均包封率为76.61%。     

荞麦糖肽脂质体的制备及其稳定性和缓释研究

为提高荞麦糖肽(buckwheat glycopeptide,BG)的生物利用率,本研究首先对制备所得的BG进行稳定性分析,随后利用反向蒸发法制备荞麦糖肽脂质体(buckwheat glycopeptide liposomes,BGL),经响应面试验对包埋工艺进行优化,并探究其稳定性、体外缓释特性、α-葡萄糖苷酶(α-glucosidase,AGase)抑制活性和抗氧化活性。结果表明：温度(20~80 ℃)对BG的活性影响较小,碱性条件下BG极易失活。从五种磷脂中筛选出蛋黄卵磷脂制备BGL,响应面优化工艺条件为磷脂与胆固醇质量比为4.2:1,脂药比为7.5:1,水相体积为1 mL,此条件下,BGL包埋率为72.64%。BGL对高温(100 ℃)环境不耐受,在短时间(1 h)内具有广谱pH(2~10)稳定性,反复冻融5次对其渗漏率无显著影响(P＞0.05)。BGL在体外模拟胃、肠体系中表现出良好的缓释特性,24 h累计释放速率分别为（84.50±2.30）%和（60.17±1.42）%。脂质体包埋体系的建立有利于提高BG的稳定性,并对其AGase抑制和抗氧化活性表现出良好的保护作用,为荞麦糖肽脂质体开发应用提供理论依据。