Network Meta-analysis of Qi-supplementing and Yin-nourishing Chinese patent medicines in treatment of early diabetic nephropathy / 中国中药杂志

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Tumor microenvironment and redox dual stimuli-responsive polymeric nanoparticles for the effective cisplatin-based cancer chemotherapy.

The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system.1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH 6.5-6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacyin vivowith no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy.

Effect of foliage applied chitosan-based silicon nanoparticles on arsenic uptake and translocation in rice (Oryza sativa L.).

In this study, chitosan-based silicon nanoparticles (Chsi-NPs) are prepared that primarily consists of C (57.9%), O (31.3%), N (5.6%), and Si (3.5%) and are 10-180 nm in size. We then explore the effect on the foliage applied on rice planted on soil contaminated with 104 mg·kg-1 arsenic (As); low (3 mg·L-1)and high (15 mg·L-1) doses of the foliar Chsi-NPs are administered during the rice grain filling stage. The results showed that the higher dose foliar Chsi-NPs treatment reduced the As concentration in the grain by 61.2% but increased As concentration in the leaves by 47.1% compared to the control treatment. The foliar spraying of the Chsi-NPs inhibited As transport to the grain by facilitating the attachment of As to the cell wall, with higher doses of the foliar Chsi-NPs treatment increased by 8.7%. The foliar spraying of Chsi-NPs increased the malondialdehyde levels by 18.4%, the catalase activity by 49.0%, and the glutathione activity by 99.0%. These results indicated that the foliar Chsi-NPs application was effective for alleviating As toxicity and accumulation in rice. This study provides a novel method for effectively alleviating As accumulation in rice.

The complete mitochondrial genome of Annamanum lunulatum (Coleoptera: Lamiinae) and its phylogeny.

The complete mitochondrial genome of the Annamanum lunulatum is 15,610 bp in length, which contains 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and the A + T-rich region. The arrangement of genes is identical to all know longhorn beetles mitochondrial genomes. The overall AT content of the mitochondrial genome is 75.3%, whereas the AT content of A + T-rich region is 84.3%. In ML and BI phylogenetic analyses, A. lunulatum is a sister clade to Blepephaeus succinctor, and the monophyly of Lamiinae is supported.

Six complete mitochondrial genomes of mayflies from three genera of Ephemerellidae (Insecta: Ephemeroptera) with inversion and translocation of trnI rearrangement and their phylogenetic relationships.

As a small order of Pterygota (Insecta), Ephemeroptera has almost 3,500 species around the world. Ephemerellidae is a widely distributed common group of Ephemeroptera. However, the relationship among Ephemerellidae, Vietnamellidae and Teloganellidae is still in dispute. In this study, we sequenced six complete mitogenomes of three genera from Ephemerellidae (Insecta: Ephemeroptera): Ephemerella sp. Yunnan-2018, Serratella zapekinae, Serratella sp. Yunnan-2018, Serratella sp. Liaoning-2019, Torleya grandipennis and T. tumiforceps. These mitogenomes were employed to reveal controversial phylogenetic relationships among the Ephemeroptera, with emphasis on the phylogenetic relationships among Ephemerellidae. The lengths of the six mayfly mitogenomes ranged from 15,134 bp to 15,703 bp. Four mitogenomes of Ephemerella sp. Yunnan-2018, Serratella zapekinae, Serratella sp. Yunnan-2018 and Serratella sp. Liaoning-2019 had 22 tRNAs including an inversion and translocation of trnI. By contrast, the mitogenomes of T. tumiforceps and T. grandipennis had 24 tRNAs due to an extra two copies of inversion and translocation of trnI. Within the family Ephemerellidae, disparate gene rearrangement occurred in the mitogenomes of different genera: one copy of inversion and translocation trnI in the genera Ephemerella and Serratella, and three repeat copies of inversion and translocation of trnI in the genus Torleya. A large non-coding region (≥200 bp) between trnS1 (AGN) and trnE was detected in T. grandipennis and T. tumiforceps. Among the phylogenetic relationship of the Ephemeroptera, the monophyly of almost all families except Siphlonuridae was supported by BI and ML analyses. The phylogenetic results indicated that Ephemerellidae was the sister clade to Vietnamellidae whereas Teloganellidae was not a sister clade of Ephemerellidae and Vietnamellidae.

Polyethylenimine-based nanovector grafted with mannitol moieties to achieve effective gene delivery and transfection.

Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy.

Construction of redox-responsive tumor targeted cisplatin nano-delivery system for effective cancer chemotherapy.

Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic.

Enhance transgene responses through improving cellular uptake and intracellular trafficking by bio-inspired non-viral vectors.

BACKGROUND: Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. RESULTS: A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. CONCLUSIONS: This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.

Predictive Value of Pin1 in Cervical Low-Grade Squamous Intraepithelial Lesions and Inhibition of Pin1 Exerts Potent Anticancer Activity against Human Cervical Cancer.

Many oncogenes are involved in the progression from low-grade squamous intraepithelial lesions (LSILs) to high-grade squamous intraepithelial lesions (HSILs); which greatly increases the risk of cervical cancer (CC). Thus, a reliable biomarker for risk classification of LSILs is urgently needed. The prolyl isomerase Pin1 is overexpressed in many cancers and contributes significantly to tumour initiation and progression. Therefore, it is important to assess the effects of cancer therapies that target Pin1. In our study, we demonstrated that Pin1 may serve as a biomarker for LSIL disease progression and may constitute a novel therapeutic target for CC. We used a the novel Pin1 inhibitor KPT-6566, which is able to covalently bind to Pin1 and selectively target it for degradation. The results of our investigation revealed that the downregulation of Pin1 by shRNA or KPT-6566 inhibited the growth of human cervical cancer cells (CCCs). We also discovered that the use of KPT-6566 is a novel approach to enhance the therapeutic efficacy of cisplatin (DDP) against CCCs in vitro and in vivo. We showed that KPT-6566-mediated inhibition of Pin1 blocked multiple cancer-driving pathways simultaneously in CCCs. Furthermore, targeted Pin1 treatment suppressed the metastasis and invasion of human CCCs, and downregulation of Pin1 reversed the epithelial-mesenchymal transition (EMT) of CCCs via the c-Jun/slug pathway. Collectively, we showed that Pin1 may be a marker for the risk of progression to HSIL and that inhibition of Pin1 has anticancer effects against CC.

The complete mitochondrial genome of Xanthomantis bimaculata (Mantodea: Iridopterygidae) and its phylogeny.

The mitochondrial genome sequence of Xanthomantis bimaculata (Mantodea: Iridopterygidae) from Yunnan, China is a circular molecule with the typical insect mitochondrial gene arrangement, which is 15,941 bp in length and contains 22 tRNAs, two rRNAs, 13 protein-coding genes, and one control region. The overall AT content of the mitogenome is 73.12% (A = 37.58%, T = 35.54%, C = 16.54%, G = 10.34%). In BI and ML phylogenetic analyses, X. bimaculata was a sister clade to Sceptuchus simplex. The monophyly of the families Iridopterygidae, Thespidae and Liturgusidae were supported.

Stem cell expansion and hepatic differentiation: Measurement of related indicators and detection methods / 中国组织工程研究

BACKGROUND: Stem cells have wide application prospects in tissue engineering, regenerative medicine, cell therapy and drug research. In recent years, the applied research, such as bioartificial liver, requires large-scale and high-quality stem cells by expansion, and final obtains hepatocytes (hepatocyte-like cells) by directional differentiation. Through this way, how to efficiently obtain the differentiated cells, with excellent consistency, powerful function and uniform expression of markers, are the key problems to be solved. OBJECTIVE: To review the detection indicators and detection methods related to the process of stem cell expansion and hepatic differentiation, summarize the indicators and methods that have been applied to online detection, discuss the limitations of some indicators and methods applied to online detection, and prospect the indicators and detection technologies expected to be applied to online detection in the future. METHODS: PubMed, Web of Science, Elsevier and CNKI databases were retrieved for the articles concerning stem cell expansion and hepatic differentiation published from 1990 to 2019. The literature related to stem cell expansion and hepatic differentiation was collected. The keywords were “stem cells; expansion; hepatic differentiation; monitoring; real-time online” in English and Chinese, respectively. A total of 93 articles were searched, and finally 53 eligible articles were selected and reviewed. RESULTS AND CONCLUSION: There are many detection indicators and detection methods for stem cell expansion and hepatic differentiation. Among them, the detection indicators of the expansion process are mainly related to the maintenance of pluripotency, metabolic activity, survival rate, and cancer transformation trend of stem cells. The process of hepatic differentiation varies with cell types, in which, the pluripotent stem cells and the mesodermal lineage adult pluripotent stem cells should differentiate into the endoderm-oriented cells and then the mature hepatocytes (hepatocyte-like cells), while the endodermal lineage adult pluripotent stem cells mainly composed of hepatic stem/progenitor cells can directly differentiate into mature hepatocytes (hepatocyte-like cells). The specific markers, survival rate and metabolic activity of cells in different stages of differentiation are the focus of detection. At present, although the detection methods based on large-scale biochemical detection and analysis equipment have high reliability, they face the problems of poor real-time performance, high cost and difficulties in integration and miniaturization. Future concerns are focused on the screening of key detection indicators, quantification of detection criteria and realization of automatic online detection during stem cell expansion and hepatic differentiation.

Construction of α-Cyclodextrin-Based Stimuli-Responsive Gene Delivery Nanovectors: In Vitro, Ex Vivo, and In Vivo Investigations.

Stimuli-responsive materials are promising paradigm applied to construct diagnostic and therapeutic intracellular controlled release vectors, while highlighting many challenges and opportunities. In this paper, six α-cyclodextrin-based supramolecular nanovectors were constructed and the efficacy of amine groups, stimuli-responsive profiles and endocytic mechanisms were investigated. The results indicated that the designed supermolecules can compact DNA to form stable complexes and display low cytotoxicity. Among them, PRPEI-2 with suitable PEI amine group exhibited enhanced transfecting performance, high dilution stability, nice serum compatibility, and good acid-responsive profiles to enable endosome escape, significantly higher than commercially available transfecting agent PEI25000, the most effective vector studied to date. The endocytic uptake mechanisms involved in the transfection was mainly through clathrin-mediated pathway, which is closely associated with and can be improved by endosome escape. Moreover, PRPEI-2/DNA polyplex can be effectively expressed in vivo even after 48 h via only single tail-vein injection, and the gene expression and main tissue distribution appeared in the testis, liver, brain and spleen. These excellent characteristics demonstrated that the supramolecular PRPEI-2 represents an excellent prospect as stimuli-responsive nanovectors for gene diagnosis and therapy.

The complete mitochondrial genome of Mantis religiosa (Mantodea: Mantidae) from Canada and its phylogeny.

The complete mitochondrial genome of Mantis religiosa (Mantodea: Mantidae) from Canada was successfully sequenced. The mitochondrial genome was a circular molecule of 15,521 bp in length, containing 13 protein-coding genes, two rRNA genes, 23 tRNA genes (including an extra tRNAArg gene), and the control region. The AT content of the whole genome was 76.9% and the length of the control region was 636 bp with 81.9% AT content. The structure of the M. religiosa mitochondrial genome from Canada was almost identical to M. religiosa from China and their genetic distance was just 0.017. In Bayesian inference (BI) and maximum likelihood (ML) analyses, we found that M. religiosa was a sister clade to Statilia sp. and the monophyly of the genera Hierodula and Rhombodera was not supported.

The mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) from Fujian and the phylogeny of Caenidae within Ephemeroptera.

The phylogenetic relationship of Caenidae remains hotly debated within the Ephemeroptera. We sequenced the complete mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) to discuss the phylogenetic relationships among the Caenidae. The mitochondrial genome of Caenis sp. collected from Jian'ou, Fujian province, China is a circular molecule of 15,392 bp in length containing 37 genes (13 protein-coding genes, 22 tRNAs, and two rRNAs), which showed the typical insect mitochondrial gene arrangement. In BI and ML phylogenetic trees using 23 species from 13 families, the monophyly of the families Caenidae, Heptageniidae, Isonychiidae, and Vietnamellidae was strongly supported. The clade of Caenidae is a sister clade to the clade of Teloganodidae and Baetidae.

Anti-Helicobacterpylori effectiveness and targeted delivery performance of amoxicillin-UCCs-2/TPP nanoparticles based on ureido-modified chitosan derivative.

The amoxicillin-UCCs-2/TPP nanoparticles constructed with ureido-modified chitosan derivative UCCs-2 and sodium tripolyphosphate (TPP) played an important role to deliver drug to achieve more efficacious and specific eradication of Helicobacterpylori (H. pylori) in vitro. In this study, the anti-H. pylori effectiveness in vivo and uptake mechanism was investigated in details, including the effect of temperature, pH values and the addition of competitive substrate urea on uptake. Compared with unmodified nanoparticles, a more efficacious and specific anti-H. pylori activities were obtained in vivo by using this biological chitosan derivative UCCs-2. Histological staining and immunological analysis verified that the amoxicillin-UCCs-2/TPP nanoparticles could diminish the proinflammatory cytokines levels and alleviate the inflammatory damages caused by H. pylori infection. The uredio-modified nanoparticles also have favorable gastric retention property, which is beneficial for the oral drug delivery to targeted eradicate H. pylori infection in stomach. These findings suggest that this targeted drug delivery system may serve for specific treatment of H. pylori infection both in vitro and in vivo, which can also be used as promising nanocarriers for other therapeutic reagents to target H. pylori.

Construction and optimization of pH-sensitive nanoparticle delivery system containing PLGA and UCCs-2 for targeted treatment of Helicobacter pylori.

The acidic environment of the stomach is a threat to the curative effect of antimicrobial drugs for the eradication of Helicobacter pylori (H. pylori) in the infected area. The conventional clinical formulations of antibiotics have low specificity to H. pylori, which disrupts the normal balance of intestinal microbiomes. Therefore, oral drug delivery system with better stability at low pH as well as higher specificity to target H. pylori would provide more effective strategy to eradicate H. pylori and reduce the side effect of antibiotics. Based on the construction of UreI-mediated targeted drug delivery system developed by our group, in this work, using urea-modified UCCs-2 as targeting moiety to the UreI channel protein which is specifically expressed on H. pylori, pH-sensitive amoxicillin-loaded AMX-PLGA/UCCs-2 nanoparticles produced by UCCs-2 and PLGA for targeted treatment of H. pylori infection were established. The nanoparticles were prepared by double emulsion-solvent evaporation method. To achieve a promising drug delivery system with favorable pH-sensitive properties, we adopted an orthogonal design to obtain the optimal formulation. The results showed that the optimized AMX-PLGA/UCCs-2 nanoparticles were in a favorable pH sensitive manner and exhibited low cytotoxicity, higher specificity and better anti-H. pylori efficiency than amoxicillin and non-targeting AMX-PLGA/Cs nanoparticle both in vitro and in vivo, which can protect the antimicrobial drugs against acidic environment and deliver them to targeted eradicate H. pylori in the infected location. The cellular uptake mechanism showed that AMX-PLGA/UCCs-2 nanoparticles are an effective UreI-mediated targeted drug delivery system for anti-H. pylori treatment, which can also be used as promising nanocarriers for oral delivery of other therapeutic drugs to targeted treat H. pylori.

Construction and evaluation of BSA-CaP nanomaterials with enhanced transgene performance via biocorona-inspired caveolae-mediated endocytosis.

Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

Toxicity Research of PM2.5 Compositions In Vitro.

According to the published literature, we surmise that particulate matter (PM) concentration, individually, may be less important than components in explaining health effects. PM2.5 (aerodynamic diameter <2.5 µm) had similar cytotoxicity (e.g., cell viability reduction, oxidative damage, inflammatory effects and genetic toxicity) on different types of cells. The studies of cells are readily available for detailed mechanistic investigations, which is more appropriate for learning and comparing the mechanism caused by single or mixed ingredients coating a carbon core. No review exists that holistically examines the evidence from all components-based in vitro studies. We reviewed published studies that focus on the cytotoxicity of normal PM2.5. Those studies suggested that the toxicity of mixed compositions differs greatly from the single ingredients in mixed components and the target cells. The cytotoxic responses caused by PM2.5 components have not shown a consistent association with clear, specific health effects. The results may be beneficial for providing new targets for drugs for the treatment of PM2.5-related diseases.

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

The covalently cross-linked chitosan-poly(ethylene glycol)1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG1540-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG1540H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.

Cholesterol derived cationic lipids as potential non-viral gene delivery vectors and their serum compatibility.

Cholesterol derivatives M1-M6 as synthetic cationic lipids were designed and the biological evaluation of the cationic liposomes based on them as non-viral gene delivery vectors were described. Plasmid pEGFP-N1, used as model gene, was transferred into 293T cells by cationic liposomes formed with M1-M6 and transfection efficiency and GFP expression were tested. Cationic liposomes prepared with cationic lipids M1-M6 exhibited good transfection activity, and the transfection activity was parallel (M2 and M4) or superior (M1 and M6) to that of DC-Chol derived from the same backbone. Among them, the transfection efficiency of cationic lipid M6 was parallel to that of the commercially available Lipofectamine2000. The optimal formulation of M1 and M6 were found to be at a mol ratio of 1:0.5 for cationic lipid/DOPE, and at a N/P charge mol ratio of 3:1 for liposome/DNA. Under optimized conditions, the efficiency of M1 and M6 is greater than that of all the tested commercial liposomes DC-Chol and Lipofectamine2000, even in the presence of serum. The results indicated that M1 and M6 exhibited low cytotoxicity, good serum compatibility and efficient transfection performance, having the potential of being excellent non-viral vectors for gene delivery.