Molecular Dynamics Simulations of Polymer Nanocomposites Welding: Interfacial Structure, Dynamics and Strength.

Polymer welding has received numerous scientific attention, however, the welding of polymer nanocomposites (PNCs) has not been studied yet. In this work, via coarse-grained molecular dynamics simulation, the attention on investigating the welding interfacial structure, dynamics, and strength by constructing the upper and lower layers of PNCs, by varying the polymer-nanoparticle (NP) interaction strength εNP-p is focused. Remarkably, at low εNP-p , the NPs gradually migrate into the top and bottom surface layer perpendicular to the z direction during the adhesion process, while they are distributed in the middle region at high εNP-p . Meanwhile, the dimension of polymer chains is found to exhibit a remarkable anisotropy evidenced by the root-mean-square radius of gyration in the xy- (Rg,xy ) and z- (Rg,z ) component. The welding interdiffusion depth increases the fastest at low εNP-p , attributed to the high mobility of polymer chains and NPs. Lastly, although the mechanical properties of PNCs at high εNP-p is the strongest because of the presence of the NPs in the bulk region, the welding efficiency is the greatest at low εNP-p . Generally, this work provides a fundamental understanding of the interfacial welding of PNCs, in hopes of guiding to design and fabricate excellent self-healable PNCs.

pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration. RESULTS: A hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms. CONCLUSION: ICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.

Polysiloxane-Based Polyurethanes with High Strength and Recyclability.

Polysiloxanes have attracted considerable attention in biomedical engineering, owing to their inherent properties, including good flexibility and biocompatibility. However, their low mechanical strength limits their application scope. In this study, we synthesized a polysiloxane-based polyurethane by chemical copolymerization. A series of thermoplastic polysiloxane-polyurethanes (Si-TPUs) was synthesized using hydroxyl-terminated polydimethylsiloxane containing two carbamate groups at the tail of the polymer chains 4,4'-dicyclohexylmethane diisocyanate (HMDI) and 1,4-butanediol as raw materials. The effects of the hard-segment content and soft-segment number average molecular weight on the properties of the resulting TPUs were investigated. The prepared HMDI-based Si-TPUs exhibited good microphase separation, excellent mechanical properties, and acceptable repeatable processability. The tensile strength of SiTPU-2K-39 reached 21.5 MPa, which is significantly higher than that of other flexible polysiloxane materials. Moreover, the tensile strength and breaking elongation of SiTPU-2K-39 were maintained at 80.9% and 94.6%, respectively, after three cycles of regeneration. The Si-TPUs prepared in this work may potentially be used in gas separation, medical materials, antifouling coatings, and other applications.

Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy.

The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2-PEG-LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2-PEG-LP@CaAs was investigated both in vitro and in vivo. As a result, A2-PEG-LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2-PEG-LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.

Angiopep-2 modified lipid-coated mesoporous silica nanoparticles for glioma targeting therapy overcoming BBB.

Glioma is the most typical malignant brain tumor, and the chemotherapy to glioma is limited by poor permeability for crossing blood-brain-barrier (BBB) and insufficient availability. In this study, angiopep-2 modified lipid-coated mesoporous silica nanoparticle loading paclitaxel (ANG-LP-MSN-PTX) was developed to transport paclitaxel (PTX) across BBB mediated by low-density lipoprotein receptor-related protein 1 (LRP1), which is over-expressed on both BBB and glioma cells. ANG-LP-MSN-PTX was characterized with homogeneous hydrodynamic size, high drug loading capacity (11.08%) and a sustained release. In vitro experiments demonstrated that the targeting efficiency of PTX was enhanced by ANG-LP-MSN-PTX with higher penetration ability (10.74%) and causing more C6 cell apoptosis. ANG-LP-MSN-PTX (20.6%) revealed higher targeting efficiency compared with LP-MSN-PTX (10.6%) via blood and intracerebral microdialysis method in the pharmacokinetic study. The therapy of intracranial C6 glioma bearing rats was increasingly efficient, and ANG-LP-MSN-PTX could prolong the survival time of model rats. Taken together, ANG-LP-MSN-PTX might hold great promise as a targeting delivery system for glioma treatment.

Correction: Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers.

Correction for 'Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers' by Fan Qu et al., Soft Matter, 2020, 16, 10454-10462, DOI: .

Construction of a Pyrimidine Framework through [3 + 2 + 1] Annulation of Amidines, Ketones, and N,N-Dimethylaminoethanol as One Carbon Donor.

An efficient, facile, and eco-friendly synthesis of pyrimidine derivatives has been developed. It involves a [3 + 2 + 1] three-component annulation of amidines, ketones, and one carbon source. N,N-Dimethylaminoethanol is oxidized through C(sp3)-H activation to provide the carbon donor. One C-C and two C-N bonds are formed during the oxidative annulation process. The reaction shows good tolerance to many important functional groups in air, making this methodology a highly versatile alternative, and significant improvement to the existing methods for structuring a pyrimidine framework, especially 4-aliphatic pyrimidines.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

iRGD and TGN co-modified PAMAM for multi-targeted delivery of ATO to gliomas.

A poly(amidoamine) dendrimer (PAMAM, G5) based drug delivery system was developed for the treatment of glioma. PAMAM was modified with polyethylene glycol (PEG) to improve its in vivo stability and reduce immunogenicity. Further, the internalized RGD (iRGD) recognition ligand of the integrin αvß3 receptor and the blood-brain barrier (BBB)-targeting group TGN were introduced. Arsenic trioxide (ATO) was loaded into the internal cavity through electrostatic interactions to form iRGD/TGN-PEG-PAMAM-ATO. The drug delivery system of iRGD/TGN dual-modified PAMAM, which entrapped ATO, had a high entrapment efficiency of approximately 71.92% ± 1.17% and displayed sustainable acid-dependent drug release. Assessment of antiglioma effects revealed that survival rate was significantly higher in the iRGD/TGN comodified group than in the other groups. Overall, iRGD/TGN-based dual targeting by combining nanocarriers and targeting technology increased the amount of drug that crossed BBB, thus achieving targeted enrichment and activation of the drug in tumor tissue. This activation ultimately increased therapeutic effects and reduced side effects of ATO. This strategy using a multistep-targeted delivery system shows great promise for targeted glioma therapy.

Synergistic effect in improving the electrical conductivity in polymer nanocomposites by mixing spherical and rod-shaped fillers.

In this work, coarse-grained molecular dynamics simulation is adopted to investigate the effect of hybrid fillers [nanospheres (NSs) and nanorods (NRs)] on the conductive probability of polymer nanocomposites (PNCs) in the quiescent state and under the shear field. The percolation threshold gradually rises as the volume fraction ratio (α) of NSs to all the fillers increases in the quiescent state. Compared to the NSs, the greater number of beads in the NRs help them connect to other NRs to form the conductive network. Meanwhile, compared to NSs, more NRs participate in building the conductive network. A transition from the synergistic effect to the antagonistic effect occurs as the NS-NR tunneling distance is reduced. Furthermore, the shear field induces a more direct aggregation structure of NSs, which act as linkers between fillers to protect the conductive network. This result is confirmed by the fact that more NSs occupy the conductive network under the shear field. As a result, the percolation threshold declines with increasing shear rate. Finally, compared to in the quiescent state, the percolation threshold increases at α = 0.0 and remains nearly unchanged for α = 0.25 under the shear field, while it gradually decreases for α≥ 0.5. In total, the results further our understanding of how to realize the synergistic effect between NSs and NRs when forming a conductive network of PNCs.

Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy.

This study proposed a new nonviral gene delivery system for thrombus targeting therapy based on PEGlyation polyamides dendrimer (PAMAM) modified with RGDyC to condense the pDNA with recombinant hirudine (rHV) gene (RGDyC-rHV-EGFP). The RGDyC-mPEG-PAMAM was synthesized and characterized by 1H NMR, PAMAM/pDNA was characterized by particle size, zeta potential, cellular uptake, and gel retraction assay. The transfection was carried out between lipofectamine 2000 and PAMAM/pDNA on HUVEC cells at various N/P ratios. The antithrombotic effect in vivo was evaluated by venous thrombosis model on Wistar rats. It showed that the drug delivery system of RGDyC modified PAMMA, which entrapped pDNA could significantly improve the transfection efficiency. It was about 7.56-times higher than that of lipofectamine 2000. In addition, the expression level of hirudine fusion protein was the highest at N/P ratio of 0.5. The results of antithrombotic effect showed that the weight of thrombus was reduced in RGDyC modified group; compared with heparin group, there was no significant difference ( P > 0.05). Overall, we take the advantage of the unique advantages of hirudine, combining the genetic engineering, nanocarriers, and targeting technology, to achieve the targeted enrichment and activation the hirudine fusion protein in the thrombus site, to improve the concentration of drugs in the thrombus site, finally increasing the curative effect and reduce the risk of bleeding. The strategy of gene delivery system holds unique properties as a gene delivery system and has great promises in thrombus targeting therapy.

Angiopep-2-Conjugated "Core-Shell" Hybrid Nanovehicles for Targeted and pH-Triggered Delivery of Arsenic Trioxide into Glioma.

The poor capability of drugs to permeate through the blood-brain barrier (BBB) and further release inside glioma greatly limits the curative effects of glioma chemotherapies. In this study, we prepared angiopep-2-conjugated liposome-silica hybrid nanovehicles for targeted delivery and increased the permeation of arsenic trioxide (ATO) in glioma. Polyacrylic acid (PAA) was grafted on mesoporous silica nanoparticles (MSN) for pH-sensitive release and supporting the lipid membrane. The prepared "core-shell" nanovehicles (ANG-LP-PAA-MSN) were characterized with uniform size, high drug loading efficiency (8.19 ± 0.51%), and superior pH-sensitive release feature. From the experiments, the enhanced targeted delivery of ATO by ANG-LP-PAA-MSN (ANG-LP-PAA-MSN@ATO) was evidenced by the improvement of transport, enhanced cellular uptake, and apoptosis in vitro. In addition, the pharmacokinetic study was creatively carried out through the blood-glioma synchronous microdialysis and revealed that the half-life ( t1/2) of blood and glioma tissue in the ANG-LP-PAA-MSN@ATO treatment group was extended by 1.65 and 2.34 times compared with the ATO solution group (ATO-Sol). The targeting efficiency of ANG-LP-PAA-MSN@ATO (24.96%) was dramatically stronger than that of the ATO-Sol (5.94%). Importantly, ANG-LP-PAA-MSN@ATO had a higher accumulation (4.6 ± 2.6% ID per g) in tumor tissues and showed a better therapeutic efficacy in intracranial C6 glioma bearing rats. Taken together, the blood-glioma synchronous microdialysis was successful used for the pharmacokinetic study and real-time monitoring of drug concentrations in blood and glioma; ANG-LP-PAA-MSN could be a promising targeted drug delivery system for glioma therapy.

Molecular dynamics simulation study of the fracture properties of polymer nanocomposites filled with grafted nanoparticles.

By employing coarse-grained molecular dynamics simulations, we investigated the fracture behavior of polymer nanocomposites (PNCs) filled with polymer-grafted nanoparticles (NPs) in detail by particularly regulating the grafting density and the length of the grafted chain. By calculating their fracture energy, we observed that their rupture properties first increase and then decrease with the increase of the grafting density or the length of the grafted chains. Their bond orientation degree and their van der Waals energy change are characterized to understand their fracture behavior. To further explain it, we analyzed the contributions of the matrix chains, grafted chains, and NPs to the total stress. It is interesting to find that the stress borne by one bead of matrix chains or NPs gradually increases with the grafting density, while the stress borne by the grafted chains first increases and then decreases. In addition, the stress borne by one bead of matrix chains or grafted chains gradually increases with the length of the grafted chains, while the stress borne by NPs remains nearly unchanged. As a result of these contributions, the optimal fracture properties appear at the moderate grafting density or length of the grafted chain. Then, the number of voids is quantified, which first increases and then decreases with strain because of the coalescence of small voids into large ones. Accompanying this, the maximum void size increases significantly. Furthermore, the maximum number of voids increases with the grafting density, while it is nearly independent of the length of the grafted chain. In particular, the voids are preferably generated at the end beads of the chains or at the surfaces of the NPs. In summary, this work could provide some further understanding of how the grafted chains affect the fracture properties of the PNCs.

Asiatic acid enhances intratumor delivery and the antitumor effect of pegylated liposomal doxorubicin by reducing tumor-stroma collagen.

Tumor-targeted drug delivery systems (Tt-DDSs) are proposed as a promising strategy for cancer care. However, the dense collagen network in tumors stroma significantly reduces the penetration and efficacy of Tt-DDS. In order to investigate the effect of asiatic acid (AA) on antitumor effect of pegylated liposomal doxorubicin (PLD) by attenuating stroma-collagen, colon cancer xenograft mice (SW620 cell line) were treated by PLD, AA, or combined regimes, respectively; the collagen levels were estimated by Sirius red/fast green dual staining and immunohistochemistry (IHC) staining; the intratumor exposure of doxorubicin was visualized by ex vivo fluorescence imaging and quantified by HPLC/MS analysis. In addition, the impact of AA on collagen synthesis of fibroblast cell (HFL-1) and cytotoxic effect of PLD and doxorubicin to cancer cell (SW620) were studied in vitro. In the presence of AA (4 mg/kg), the intratumor collagen level was restricted in vivo (reduced by 22%, from 4.14% ± 0.30% to 3.24% ± 0.25%, P = 0.051) and in vitro. Subsequently, doxorubicin level was increased by ~30%. The antitumor activity of PLD was significantly improved (57.3% inhibition of tumor growth and 44% reduction in tumor weight) by AA combination. Additionally, no significant improvement in cytotoxic effect of PLD or doxorubicin induced by AA was observed. In conclusion, AA is a promising sensitizer for tumor treatment by enhancing intratumor drug exposure via stromal remodeling.

Intranasal administration of pullulan-based nanoparticles for enhanced delivery of adriamycin into the brain: in vitro and in vivo evaluation.

Intranasal (i.n.) administration is an efficient route for enhancing drug delivery to the brain, bypassing the blood-brain barrier (BBB) and eliminating systemic side effects. The purpose of this study was to investigate the nose-to-brain delivery efficiency of adriamycin (ADM) loaded in cholesterol-modified pullulan self-assembled nanoparticles (CHSP-SAN) via i.n. administration. The prepared nanodrugs (ADM-CHSP-SAN) were characterized as uniform size (112.8±1.02 nm), high drug loading capacity (7.65±0.58 %), and sustained release. CHSP-SAN showed good biocompatibility and low toxicity on HBMEC and C6 cells. The enhanced delivery of ADM across the BBB with CHSP-SAN was demonstrated by the reduced half maximal inhibitory concentration (IC50) value and the increased apoptosis proportion of C6 cells. The pharmacokinetics of ADM-CHSP-SAN was accessed by cerebral microdialysis technique. The pharmacokinetic results showed higher peak concentration (Cmax), area under the curve (AUC0-12h) and shorter peak time (Tmax) after i.n. administration that after intravenous (i.v.) administration. The i.n. administration of CHSP-SAN greatly increased ADM availability in cerebral tissue compared to that of ADM solution. Collectively, CHSP-SAN strikingly increased ADM transport across the BBB and improved its availability in brain via i.n. administration.

[Preparation of angiopep-2-modified FITC-labeled neurotoxin nanoparticles and in vitro release characteristics].

In order to prepare angiopep-2 modified fluorescein isothiocyanate-labeled neurotoxin nanoparticles( ANG-NPs/FITCNT),emulsion/solvent evaporation method was used with m PEG-PLA and ANG-PEG-PLA( in proper proportions) as carriers and with FITC-NT as drug. With particle size and encapsulation efficiency as comprehensive indexes,the effects of different ultrasound power and ultrasound time combinations on the process were investigated. The in vitro release characteristics of nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were investigated by dialysis method. The results indicated that the optimum process for preparing ANG-NPs/FITC-NT was as follows: ultrasonic power 90 W,ultrasonic time 30 s. In such optimal process,ANG-NPs/FITC-NT were well-shaped under the transmission electron microscope,with an average particle size of( 123. 9±0. 5) nm,Zeta potential of(-10. 5±0. 5) m V,encapsulation efficiency of( 68. 1±0. 4) %,and the drug loading of( 0. 82±0. 01) %. The in vitro drug release profiles of the nanoparticles in PBS buffer at p H 7. 4 and p H 6. 5 were both consistent with Ritger-Peppas equation,ln Q = 0. 508 8 lnt-2. 285 0,r = 0. 961 5( p H 7. 4) and ln Q= 0. 449 9 lnt-1. 855 3,r = 0. 970 3( p H 6. 5),respectively. The experiment results proved that the nanoparticles prepared by emulsion/solvent evaporation method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristic,which might be a potential carrier for NT intracerebral drug delivery.

Effects of chemically heterogeneous nanoparticles on polymer dynamics: insights from molecular dynamics simulations.

The dispersion of solid nanoparticles within polymeric materials is widely used to enhance their performance. Many scientific and technological aspects of the resulting polymer nanocomposites have been studied, but the role of the structural and chemical heterogeneity of the nanoparticles has just started to be appreciated. For example, simulations of polymer films on planar heterogeneous surfaces revealed unexpected, non-monotonic activation energy to diffusion on varying the surface composition. Motivated by these intriguing results, here we simulate via molecular dynamics a different, fully three-dimensional system, in which the heterogeneous nanoparticles are incorporated in a polymer melt. The nanoparticles are roughly spherical assemblies of strongly and weakly attractive sites, in fractions of f and 1 - f, respectively. We show that the polymer diffusion is still characterized by a non-monotonic dependence of the activation energy on f. The comparison with the case of homogeneous nanoparticles clarifies that the effect of the heterogeneity increases on approaching the polymer glass transition.

Molecular dynamics simulation of the electrical conductive network formation of polymer nanocomposites with polymer-grafted nanorods.

Grafting chains on the surface of a filler is an effective strategy to tune and control the filler conductive network, which can be utilized to fabricate polymer nanocomposites (PNCs) with high electrical conductivity. In this work, by employing the coarse-grained molecular dynamics simulation, we investigated the effect of polymer-grafted nanorods (NRs) on the conductive probability of PNCs in the quiescent state or under the shear field for different volume fractions of the NRs. The local order structure of the NRs aggregating in the matrix is gradually broken down, and the dispersion state of the NRs improves with increasing grafting density. However, at high grafting densities, the uniform dispersion of the NRs leads to a large NR-NR distance. As a result, the conductive probability first increases and then decreases with the increase of the grafting density. Under the shear field, the conductive probability shows a continuous increase with the grafting density. Compared with that in the quiescent state, the decrease or the increase of the conductive probability depends on the grafting density under the shear field. In particular, the smallest change in the percolation threshold appears at the highest grafting density, which reflects the high conductive stability. In addition, the topological structure of the conductive network nearly remains unchanged with the length of the grafted chain. Finally, compared with the strong attractive interaction between grafted chains and free chains, weakly repulsive interactions can effectively enhance the conductive probability.

[Preparation process of norcantharidin/tetrandrine dual loaded liposomes and their in vitro release characteristics].

In order to optimize the prescription and preparation process of norcantharidin/tetrandrine dual loaded liposomes, the dual drug loaded liposomes were prepared by film dispersion-ultrasonic method using norcantharidin-mesoporous silica nanoparticles（MSN-NCTD）and tetrandrine（Tet）. With particle size and encapsulation efficiency as comprehensive indexes, the influences of phospholipid cholesterol amount, ultrasonic time and ultrasonic power on prescription process were investigated by orthogonal test; the in vitro release characteristics of liposomes were investigated by dialysis method. The results indicated that the best prescription process of prepared norcantharidin/tetrandrine dual loaded liposomes was as follows: phospholipid-cholesterol ratio 2.5:1, ultrasonic time 4 min, ultrasonic power 40%; the encapsulation efficiency was 86.62% and 79.19%respectively for NCTD and Tet;liposomes were well-shaped under the transmission microscope, with average particle size of （207.5±3.6） nm, Zeta potential of （1.345±0.173） mV; and the 48 h cumulative release rates of NCTD and Tet were 85.14% and 85.00% respectively. The experiment results proved that the dual drug loaded liposomes prepared by film dispersion-ultrasonic method had uniform particle size, high encapsulation efficiency and in vitro sustained release characteristics.

[Preparation and in vitro evaluation of arsenic trioxide glioma targeting drug delivery system loaded by PAMAM dendrimers co-modified with RGDyC and PEG].

Arsenic trioxide (ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However, its toxicity and difficulties in the permeability into the blood brain barrier (BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer (PAMAM) is a synthetic polymer with many advantages, such as a good permeability, stability and biocompatibility. Additionally, the 5th generation of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study, the 5th generation of PAMAM co-modified with RGDyC and PEG, then confirmed by ¹H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. in vitro release showed that the nanocarrier not only has the sustained release effect, but also some pH-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group in vitro. Accordingly, the drug delivery system has a better anti-tumour effect across the blood brain barrier (BBB) in vitro, which further proves the tumour targeting of RGDyC.