Preparation and characterization of porous hollow silica nanoparticles for drug delivery application

Porous hollow silica nanoparticles (PHSNP) with a diameter of 60-70 nm and wall thickness of approximately 10nm were synthesized by using CaCO(3) nano-particles as the inorganic template. The characterization of PHSNP by TEM and BET indicated that PHSNP were uniform spherical particles with good dispersion, and had a specific surface area of 867 m(2)/g. The as-synthesized PHSNP were subsequently employed as drug carrier to investigate in vitro release behavior of cefradine in simulated body fluid. UV-spectrometry and TG analyses were performed to determine the amount of cefradine entrapped in the carrier. The BJH pore size distribution of PHSNP before and after entrapping cefradine was examined. Cefradine release profile from PHSNP followed a three-stage pattern and exhibited a delayed release effect.     

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications.     

The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a novel oral drug delivery system for ibuprofen delivery

To improve the bioavailability of ibuprofen (IBU), we developed a novel binary complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU-PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS). The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent evaporation method and radical polymerization, respectively. The final OIDDS was obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH 7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied by laser granularity analyzer and transmission electron microscope (TEM). The inner structures of the pH-sensitive hydrogel chips were observed with an S-4800 scanning electron microscope (SEM). The distribution states of IBU in the OIDDS were also studied with X-ray diffraction (XRD) and differential scanning calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round shape with an average diameter about 100 nm. Fourier transform infrared spectrum (FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture showed that the final hydrogel had 3D net-work structures. Moreover, the poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC curves suggested that IBU distributed in the OIDDS with an amorphous state. The cumulated release profiles indicated that the final OIDDS could release IBU in alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore, the novel OIDDS could improve the oral bioavailability of IBU, and had a potential application in drug delivery.     

肝癌靶向载多烯紫杉醇聚多巴胺修饰琥珀酸酯-聚乳酸纳米粒子的研究

目的 建立一种简便的、具有肝癌靶向的聚多巴胺表面修饰聚合物纳米粒子以增加聚合物膜层和功能化的方法.方法 采用聚多巴胺修饰聚乙二醇1000-琥珀酸盐-聚乳酸纳米粒子(pD-TPGS-PLA/NPs),并用其包载多烯紫杉醇(DTX).为了达到靶向治疗肝癌的作用,再将半乳糖胺连接在pD-TPGS-PLA/NPs表面,从而通过配体-受体介导的作用提高DTX的递送效率.结果 聚多巴胺-琥珀酸酯-聚乳酸纳米粒子(pD-TPGS-PLA/NPs)和半乳糖胺-聚多巴胺-琥珀酸酯-聚乳酸纳米粒子(Gal-pD-TPGS-PLA/NPs)在粒径和形态学上与琥珀酸酯-聚乳酸纳米粒子(TPGS-PLA/NPs)有明显的不同.体外研究结果显示,TPGS-PLA/NPs、pD-TPGS-PLA/NPs和Gal-pD-TPGS-PLA/NPs对DTX有相似的释放行为.激光扫描共聚焦显微镜和流式细胞仪结果显示,HepG2细胞对于包载香豆素-6的Gal-pD-TPGS-PLA/NPs有较高地细胞摄取效率.相比于TPGS-PLA/NPs、pD-TPGS-PLA/NPs和临床应用的DTX药物多西他赛,载DTX的Gal-pD-TPGS-PLMNPs对HepG2细胞的生长有更强的抑制能力.体内抗肿瘤研究结果显示,在荷瘤裸鼠上注射包载DTX的Gal-pD-TPGS-PLA/NPs能有效减小肿瘤尺寸.结论 Gal-pD-TPGS-PLA/NPs可通过配体-受体识别与肝癌细胞发生特有的相互作用,有望成为一种极具潜力的靶向治疗肝癌的药物递送系统.     

Preformed albumin corona,a protective coating for nanoparticles based drug delivery system

The non-specific interaction between nanoparticles (NPs) and plasma proteins occurs immediately after NPs enter the blood, resulting in the formation of the protein corona that thereafter replaces the original NPs and becomes what the organs and cells really see. Consequently, the in vivo fate of NPs and the biological responses to the NPs are changed. This is one substantial reason for the two main problems of the NPs based drug delivery system, i.e. nanotoxicity and rapid clearance of NPs from the blood after intravenous injection. Here, we demonstrate the successful application of the preformed albumin corona in inhibiting the plasma proteins adsorption and decreasing the complement activation, and ultimately in prolonging the blood circulation time and reducing the toxicity of the polymeric PHBHHx NPs. Since the interaction of proteins with various nano-materials and/or -particles is ubiquitous, pre-forming albumin corona has a great potential to be a versatile strategy for optimizing the NPs based drug delivery system.     

Novel delivery system based on complexation hydrogels as delivery vehicles for insulin-transferrin conjugates

A variety of approaches have been investigated to address the problems associated with oral insulin delivery, but the bioavailability of oral insulin is still low. Insulin is rapidly degraded by the enzymes in the GI tract and is not transported across the epithelial barrier easily. The oral insulin formulation developed in this work makes use of complexation hydrogels for oral delivery of insulin bioconjugates. The insulin bioconjugates synthesized in this work consist of insulin bound to transferrin molecule which can be uptaken by the epithelial cells. The conjugates can increase the permeability of insulin across the epithelial barrier by receptor-mediated transcytosis. The transferrin in the conjugate is also shown to stabilize insulin in the presence of intestinal enzymes. Use of complexation hydrogels for delivery of insulin-transferrin conjugate may greatly increase the bioavailability of oral insulin. This is because, the complexation hydrogels are known to exhibit characteristics that make them ideal candidates for oral protein delivery. They can also inhibit the degradation of insulin in the GI tract. Thus, combination of these two approaches may provide an innovative platform for oral insulin delivery.     

Comparisons of three polyethyleneimine-derived nanoparticles as a gene therapy delivery system for renal cell carcinoma

Background  

Polyethyleneimine (PEI), which can interact with negatively charged DNA through electrostatic interaction to form nanocomplexes, has been widely attempted to use as a gene delivery system. However, PEI has some defects that are not fit for keeping on gene expression. Therefore, some modifications against PEI properties have been done to improve their application value in gene delivery. In this study, three modified PEI derivatives, including poly(ε-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI (PCFC-g-PEI), folic acid-PCFC-isophorone diidocyanate-PEI (FA-PEAs) and heparin-PEI (HPEI), were evaluated in terms of their cytotoxicity and transfection efficiency in vitro and in vivo in order to ascertain their potential application in gene therapy.     

Polyelectrolytic gelatin nanoparticles as a drug delivery system for the promastigote form of Leishmania amazonensis treatment

Abstract

In this study, phthalocianato[bis(dimethylaminoethanoxy)] silicon (NzPC) was loaded onto gelatin nanoparticles functionalized with polyelectrolytes (polystyrene sulfonate/polyallylamine hydrochloride) by layer-by-layer (LbL) assembly for photodynamic therapy (PDT) application in promastigote form of Leishmania amazonensis treatment. The process yield, and encapsulation efficiency were 80.0% ± 1.8 and EE = 87.0% ± 1.1, respectively. The polyelectrolytic gelatin nanoparticles (PGN) had a mean diameter of 437.4?±?72.85?nm, narrow distribution size with a polydispersity index of 0.086. The obvious switching of zeta potential indicates successful alternating deposition of the polyanion PSS and polycation PAH directly on the gelatin nanoparticles. Photosensitizer photophysical properties were shown to be preserved after gelatin nanoparticle encapsulation. The impact of the PDT in the viability and morphology of Leishmania amazonensis promastigote in culture medium was evaluated. The PGN-NzPc presented low toxicity at the dark and the PDT was capable of decreasing the viability in more than 80% in 0.1?µmol.L^?1 concentration tested. The PDT also triggered significant morphological alterations in the Leishmania promastigotes. These results reinforce the idea that the use of PGN as photosensitizers carriers is useful for PDT of Leishmania promastigotes.     

Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-γ) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4⁺ or CD8⁺ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-γ and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.     

粉尘螨-壳聚糖疫苗经鼻免疫治疗小鼠过敏性哮喘的实验研究

探讨粉尘螨壳聚糖疫苗经鼻粘膜免疫治疗过敏性哮喘的疗效。用粉尘螨(Dermatophagoides farinae,Df)提取液致敏、激发BALB/c小鼠,复制哮喘模型,24只BALB/c小鼠随机分为空白对照组(A组)、模型组(B组)、粉尘螨对照组(C组)粉尘螨-壳聚糖疫苗治疗组(D组)。检测各组气道高反应性;通过HE(haematoxylin and eosin)染色观察小鼠肺部炎症;观察支气管肺泡灌洗液(BALF)中细胞总数和细胞分类;用酶联免疫吸附试验(ELISA)检测BALF、脾细胞培养上清的细胞因子和血清中Df特异性的IgE、IgG2a抗体。粉尘螨和粉尘螨-壳聚糖疫苗治疗组肺部变态反应性炎症病理变化较模型组明显减轻,气道高反应性Penh值下降;BALF中的细胞总数、嗜酸粒细胞(EOS)计数、IL-4、血清抗原特异性IgE抗体和脾细胞分泌IL-4均明显低于模型组,而且总体作用粉尘螨壳聚糖疫苗治疗组要强于粉尘螨对照组。粉尘螨-壳聚糖疫苗经鼻腔免疫可以治疗小鼠过敏性哮喘,且作用强于单独应用粉尘螨的对照组。     

Conjugates of poly(DL-lactide-co-glycolide) on amino cyclodextrins and their nanoparticles as protein delivery system

Poly(DL-lactide-co-glycolide) (PLG) was chemically conjugated on two amino cyclodextrins, mono(6-(2-aminoethyl)amino-6-deoxy)-beta-cyclodextrin and ethylenediamino bridged bis(beta-cyclodextrin), to afford novel amphiphilic conjugates. Those conjugates were then characterized with infrared spectrometry (IR), proton nuclear magnetic resonance ((1)H NMR) and gel permeation chromatography (GPC). A repeat-nanoprecipitation (RP-NP) method was also developed to fabricate the nanoparticles of the conjugates with a water-soluble model protein, bovine serum albumin (BSA). At the end of RP-NP process, the availability of BSA was over 80% while the entrapment efficiency was 40-50% for each nanoprecipitation. The nanoparticles were rigid and spherical with diameters of 110-180 nm determined by transmission electron microscope (TEM), atomic force microscopy (AFM) and particle size analyzer. Nanoparticles possessed good steric stability during freeze-drying and resuspensions due to the existence of cyclodextrins corona. Interactions between BSA and the conjugates in the nanoparticles were then elucidated with IR experiments. About 25% BSA adsorbed on the surface of nanoparticles due to the interaction and was easy to release in the first day. The release of BSA from the nanoparticles was in three phases: a burst effect in the first day, a followed plateau in about a week, and a sustained release of the protein over 14 days. By changing the lactide/glycolide ratio, the degradation time of the conjugates and the release rate of BSA could be controlled. The loss of CDs content was faster than that of overall Mw during degradation since CDs formed outer corona of the nanoparticles. Both the novel biomaterials and the nanosphere fabrication technique contributed to the maintenance of protein structure.     

Efficacy of nanoporous silica coatings on middle ear prostheses as a delivery system for antibiotics: An animal study in rabbits

Nanoporous silica layers are able to host molecules and release them over a certain period of time. These local drug delivery systems for antibiotics could be a new approach in the treatment of chronic otitis media. The aim of this study was to examine the efficacy of nanoporous silica coatings on middle ear prostheses as a delivery system for antibiotics in vivo. Pseudomonas aeruginosa was inoculated into the middle ear of rabbits to induce an otitis media. The control group received coated Bioverit®II implants without antibiotics. Coated prostheses with loaded ciprofloxacin were implanted into the middle ears of the study group. After 1 week, the rabbits were sacrificed. The clinical examination as well as the microbiological and histological examinations of organs and middle ear irrigation revealed clear differences between the two groups. P. aeruginosa was detected in every middle ear of the control group and was almost completely eliminated in the study group. Organ examinations revealed the presence of P. aeruginosa in the control group and a prevention of a bacterial spread in the study group. The nanoporous silica layer as antibiotic delivery system showed convincing efficacy in induced pseudomonal otitis media in the rabbit.     

Hollow mesoporous silica nanoparticles as delivery vehicle of foot-and-mouth disease virus-like particles induce persistent immune responses in guinea pigs

Foot-and-mouth disease (FMD) is an acute and febrile infectious disease, which can cause great economic losses. Virus-like particles (VLPs) as an advantageous antigen can induce significant specific immune response. To improve immunity of VLPs, especially, make it induce persistent immune response, the hollow mesoporous silica nanoparticles (HMSNs) as a potential nano-adjuvant were synthesized and loaded the FMD virus (FMDV) VLPs. They were injected into guinea pigs and the specific immune response was detected. The results confirmed that HMSNs/VLPs can induce persistent humoral immunity with high-level antibody titer for more than three months. HMSNs also improve the T-lymphocyte proliferation and IFN-γ induced by FMDV VLPs, and provides the ideal protection against FMDV challenge. These consequences indicated that HMSNs were good protein delivery vehicle and potential nano-adjuvant of vaccines.     

Polymeric micelle-templated synthesis of hydroxyapatite hollow nanoparticles for a drug delivery system

Hydroxyapatite (HA) hollow nanoparticles (HNPs) have great potential in nanoscaled delivery devices due to their small size, excellent biocompatibility and expected high capacity. However, the preparation of HA HNPs for their application in a drug delivery system has rarely been reported because HA has a complicated crystal structure and it is difficult to obtain stable HA HNPs with hollows that are only nanoscaled in size. In the present study, HA HNPs were successfully produced through a novel polymeric micelle-templating method. The micelles were structured with completely insoluble Pluronic P123 molecules at cloud point as the core and Tween-60 molecules as the shell by the hydrophobic interaction of the alkyl chains with the insoluble P123 core. The morphology of the HA HNPs could be transformed from nanospheres to nanotubes by adding citric acid as a cosurfactant. The prepared HA HNPs had a much higher drug payload than traditional nanoparticles, using vancomycin as the model drug. Most importantly, the HA nanotubes were coupled with a layer of citrate molecules on the HA surfaces, which could further improve the drug load efficiency and could form an excellent pH-controlled open/closed gate for drug release with the addition of cationic polyelectrolytes.     

A tumor-targeting near-infrared laser-triggered drug delivery system based on GO@Ag nanoparticles for chemo-photothermal therapy and X-ray imaging

In this study, a GO@Ag nanocomposite was synthesized by chemical deposition of Ag nanoparticles onto graphene oxide (GO) through a hydro thermal reaction, and doxorubicin (DOX), one of the most effective drugs against a wide range of cancers, was employed as the model drug and linked to GO@Ag via ester bonds with a very high drug loading efficiency (∼82.0%, weight ratio of DOX/GO@Ag), then GO@Ag-DOX was functionalized by DSPE-PEG2000-NGR, giving GO@Ag-DOX with active tumor-targeting capacity and excellent stability in physiological solutions. The release profiles of DOX from GO@Ag-DOX-NGR showed strong dependences on near-infrared (NIR) laser and the SPR effect of Ag nanoparticles. Compared with free DOX in an in vivo murine tumor model, GO@Ag-DOX-NGR afforded much higher antitumor efficacy without obvious toxic effects to normal organs owing to 8.4-fold higher DOX uptake of tumor and 1.7-fold higher DOX released in tumor with NIR laser than the other tissues. Besides, in this work, GO@Ag-DOX-NGR not only served as a powerful tumor diagnostic X-ray contrast agent, but also as a strong agent for photothermal ablation of tumor, the ability of GO@Ag-DOX-NGR nanoparticles to combine the local specific chemotherapy with external photothermal therapy (PTT) significantly improved the therapeutic efficacy. GO@Ag-DOX-NGR showed excellent chem-photothermal therapeutic efficacy, tumor-targeting property, NIR laser-controlled drug releasing function and X-ray imaging ability, demonstrating that there is a great potential of GO@Ag-DOX-NGR for cancer diagnosis and therapy.     

A novel controlled drug delivery system based on pH-responsive hydrogels included in soft gelatin capsules

pH-sensitive hydrogels based on methacrylic acid (MAA) and poly(ethylene glycol) macromonomer (PEGMEMA) entrapping diltiazem hydrochloride (DIL·HCl) were synthesized inside soft gelatin capsules for use as a new dosage form for oral drug administration. Different monomer compositions were used to evaluate their swelling and release behavior in two media: at low pH, simulating the acid pH of the stomach, and at pH 7, simulating the higher pH environment of the intestine. Both the swelling process and DIL·HCl release strongly depended on pH and monomer composition. Hydrogels with intermediate compositions showed diminished DIL·HCl release at pH 1.2. This fact was related to the formation of an impermeable outer skin, observed by magnetic resonance imaging (MRI). At pH 7 similar shaped release profiles were found for the four hydrogel compositions under investigation. At this neutral pH slow protonation of the carboxylate groups of MAA led to a swelling front and a dry core, also observed by MRI. As a consequence of this anomalous swelling, release curves exhibited a long period of zero order kinetics. This shows that the system could be a suitable candidate to develop a zero order release dosage form for oral administration of DIL·HCl. The swelling and dissolution processes were analyzed by different mathematical approaches.     

基于3D打印配准模板的脊柱机器人系统在椎板切除中的应用

目的 采用一款新型的脊柱机器人系统进行椎板切除操作,评估该系统的准确性。方法 取10例羊腰椎标本,对每个标本的椎板两侧进行共20次椎板切削操作。记录每次切削操作的时间,并对术后CT数据呈现的椎板切割轨迹与手术前规划的切割轨迹进行对比分析。结果 一共进行了212次垂直切削,平均每侧的椎板切削需要10.6次垂直切削来完成。单侧椎板切除的平均时间为（172.55±33.23） s。规划切割面和实际切割面在起始点的距离为（0.99±0.46） mm,在终止点的距离为（0.85±0.55） mm,切割的准确度符合预期。结论 基于3D打印配准模板的脊柱机器人系统进行椎板切除操作的精度基本满足临床要求,但仍需进一步的实验来验证。     

Effect of size on the cellular endocytosis and controlled release of mesoporous silica nanoparticles for intracellular delivery

Due to the unique physicochemical properties and membrane-permeable capacity, mesoporous silica nanoparticles (MSNs) are considered as an ideal carrier for intracellular delivery. Herein, we endeavored to address the size effect of MSNs on the cellular uptake, endosomal escape and controlled release, the key steps for the intracellular delivery. The well-ordered MSNs in the range from 55-nm to 440-nm with similar pore texture were prepared by modified base-catalyzed sol–gel method. With MC3T3-E1 model cell line, the in vitro results indicated that after 12 h cultivation, MSNs within 55 ~ 440 nm could all be internalized into the cells, and further escaped out of the endosomal compartment. The efficiency of the cellular uptake and endosomal escape strongly depended on the particle size, with the best efficiencies from 100-nm MSNs. Furthermore, the MTT results indicated that these MSNs materials were all biocompatible. The controlled release experiments with hydrophobic dexamethasone and hydrophilic vitamin C as models showed that for these small-molecular drugs, the loading amount all mainly determined by the surface area of the MSNs, and the subsequent release of the drug dramatically decreased with the increasing of the particle size. By contrast, the release rate of vitamin C was much quicker than that of the dexamethasone. These findings presented here could provide new means to tailor the size of MSNs and thus to guide the design of MSNs-based intracellular delivery system. Due to the good cell biocompatibility, high cellular uptake and endosomal escape, we conjectured that the 100-nm MSNs are more favorable for the intracellular delivery of drugs in live cells.     

Multi-core vesicle nanoparticles based on vesicle fusion for delivery of chemotherapic drugs

The Pluronic nanoparticles (NPs) composed of Pluronic (F-68) and liquid polyethylene glycol (PEG, molecular wt: 400) containing docetaxel (DTX) were stabilized with the vesicle fusion. When DTX-loaded Pluronic NPs were mixed with vesicles in the aqueous medium, DTX-loaded Pluronic NPs were incorporated into vesicles to form multi-core vesicle NPs. The morphology and size distribution of multi-core vesicle NPs were observed using FE-SEM, cryo-TEM and a particle size analyzer. To apply multi-core vesicle NPs as a delivery system for DTX, a model anti-cancer drug, the release pattern of DTX was observed and the tumor growth was monitored by injecting the DTX-loaded multi-core vesicle NPs into the tail veins of tumor-bearing mice. We also evaluated the time-dependent excretion profile, in?vivo biodistribution, circulation time, and tumor targeting capability of multi-core vesicle NPs using a non-invasive live animal imaging technology.     

Development of lipid particles targeted via sugar-lipid conjugates as novel nuclear gene delivery system

Efficient nuclear gene delivery is essential for successful gene therapy. This study developed a novel system that mimics the mechanism of nuclear entry of adenovirus (Ad) by means of a Multifunctional Envelope-type Nano Device (MEND). In this system, plasmid DNA (pDNA) was condensed with polycation, followed by encapsulation in a lipid membrane. To target MEND to the nuclear pore complex (NPC), sugar served as a NPC-mediated nuclear targeting device was modified on the surface of the lipid envelope. This was accomplished via synthesis of a sugar-cholesterol conjugate. After binding of the MEND to the NPC, the pDNA core was transferred into the nucleus in conjunction with a breakdown of the lipid envelope. Sugar-modified MEND showed higher transfection efficiency compared with unmodified MEND, in non-dividing and dividing cells. Confocal microscopy confirmed that nuclear transfer of pDNA was improved by sugar modification of MEND. Furthermore, destabilization of the lipid envelope significantly enhanced transfection activity: therefore, nuclear-delivery efficiency was closely related to lipid envelope stability. Moreover, quantitative evaluation of cellular uptake and nuclear transfer processes by real-time PCR confirmed that the surface sugars affected nuclear transfer, but not cellular uptake. In summary, a novel system for the nuclear delivery of pDNA was successfully developed by using a sugar-modified MEND and by optimizing the lipid envelope stability.