Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease.

BACKGROUND: Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. RESULTS: Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs. CONCLUSION: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.

Novel Class of Ultrasound-Triggerable Drug Delivery Systems for the Improved Treatment of Tumors.

The controlled release of anticancer drugs at the tumor site is a central challenge in treating cancer. To achieve this goal, our strategy was based on tumor-specific targeting and ultrasound-triggered release of an anticancer agent from liposomal nanocarriers. To enhance the ultrasound-triggered drug release, we incorporated a lipophilic sonosensitizer, chlorin e6 (Ce6) ester, into the lipid bilayer of liposomes. Additionally, asparagine-glycine-arginine (NGR) that binds to CD13, which is overexpressed in tumor cells, was introduced into these liposomes. Under the navigation effects of the NGR, the novel ultrasound-triggerable NGR-modified liposomal nanocarrier (NGR/UT-L) accumulates in tumor sites. Once irradiated by ultrasound in tumor tissues, the sonodynamic effect produced by Ce6 could create more efficient disruptions of the lipid bilayer of the liposomal nanocarriers. After encapsulating doxorubicin (DOX) as the model drug, the ultrasound triggered lipid bilayer breakdown can spring the immediate release of DOX, making it possible for ultrasound-responsive chemotherapy with great selectivity. By combining tumor-specific targeting and stimuli-responsive controlled release into one system, NGR/UT-L demonstrated a perfect antitumor effect. Moreover, this report provides an example of controlled-release by means of a novel class of ultrasound triggering systems.

Defect Passivation in Quasi-2D Perovskite Light-Emitting Diodes by an Ibuprofen Additive.

It is well known that the inferior film morphology and the excessive surface/interface defect states are two obstacles to achieving high electroluminescence performance of quasi-2D perovskite light-emitting diodes (PeLEDs). To solve these problems, ibuprofen was introduced as an additive in the quasi-2D perovskite emitting layer. More efficient photoluminescence is demonstrated. Further, optimized quasi-2D PeLEDs with a current efficiency of 55.93 cd/A are confirmed and 5.7-fold enhancement in device stability is obtained. The physical mechanism of the remarkable improvement is investigated by kinds of measurements. Three aspects should be counted into it. First, the introduction of ibuprofen can passivate defects, thus making the quasi-2D perovskite emitting layer more dense and homogeneous. The reason should be that the C═O functional group and C═C bond in the benzene ring in ibuprofen can coordinate the unsaturated Pb2+ perovskite emitting layer. Meanwhile, the related exciton harvesting process is investigated. The proportion of the crystalline phases (small n and large n phase) can be tuned to benefit the energy funneling process. Finally, the analysis of the current density and voltage curves of the hole-dominated devices and the electron-dominated devices is conducted by utilizing the space charge-limited current (SCLC) methods.

Silicon-based material with spiro-annulated fluorene/triphenylamine as host and exciton-blocking layer for blue electrophosphorescent devices.

A novel silicon-based compound, 10-phenyl-2'-(triphenylsilyl)-10H-spiro[acridine-9,9'-fluorene] (SSTF), with spiro structure has been designed, synthesized, and characterized. Its thermal, electronic absorption, and photoluminescence properties were studied. Its energy levels make it suitable as a host material or exciton-blocking material in blue phosphorescent organic light-emitting diodes (PhOLEDs). Accordingly, blue-emitting devices with iridium(III) bis[(4,6-difluorophenyl)-pyridinato-N,C(2)']picolinate (FIrpic) as phosphorescent dopant have been fabricated and show high efficiency with low roll-off. In particular, 44.0 cd A(-1) (41.3 lm W(-1)) at 100 cd m(-2) and 41.9 cd A(-1) (32.9 lm W(-1)) at 1000 cd m(-2) were achieved when SSTF was used as host material; 28.1 lm W(-1) at 100 cd m(-2) and 20.6 lm W(-1) at 1000 cd m(-2) were achieved when SSTF was used as exciton-blocking layer. All of the results are superior to those of the reference devices and show the potential applicability and versatility of SSTF in blue PhOLEDs.

Management of SARS-CoV-2 Omicron Variant Community Screenings in Shanghai, China: A Cross-Sectional Study.

Background: Community screening for SARS-CoV-2 Omicron variant plays a significant role in controlling the spread of infection. However, loopholes may exist in the current management of community screening in Shanghai, China. The objective of this study was to discover loopholes in the management of community screening for SARS-CoV-2 Omicron variant in Shanghai, China and provide targeted solutions. Methods: The cross-sectional study was carried out April 4 to April 30, 2021, among residential committee directors from the Putuo District, Pudong District, and Minhang District of Shanghai, China. Data were collected using a self-designed questionnaire about the management of nucleic acid testing (NAT) sampling in communities through the network platform powered by www.wjx.cn. Results: A total of 203 residential committee directors responded to the survey. Of them, 47.3% were not accepted training and 40.4% were not aware of cross-infection. Comparison among sampling sites and communities, high-risk group contained lower proportion of community training (P = 0.093~0.200), higher awareness of cross-infection (P = 0.039~0.777), more medical workers (P = 0.007~0.724) and more tests performed (P = 0.001~0.992). Larger communities had more medical workers, sampling sites, sampling tables (P = 0.000) and higher awareness of cross-infection (P = 0.009), but lower proportion of community training (P = 0.051). Conclusion: Overall, community training and awareness of infection control were inadequate. Government or institutions should organize the community training and raise the awareness of infection control. Significant differences exist in NAT management patterns between sampling sites, as well as communities of different sizes. Residential community directors minimize high-risk sampling point settings in the future. Special personnel designated by the government or institutions should tour to guide each sampling site.

New dibenzofuran/spirobifluorene hybrids as thermally stable host materials for efficient phosphorescent organic light-emitting diodes with low efficiency roll-off.

A new class of host materials DBFSF (DBFSF2 and DBFSF4) is facilely synthesized through a Suzuki coupling reaction between dibenzofuran and spirobifluorene. Their thermal, electrochemical, electronic absorption and photoluminescent properties are fully investigated. High glass transition temperatures (T(g)) of 115 °C and 124 °C are observed for DBFSF2 and DBFSF4, respectively, due to the introduction of bulky spirobifluorene groups. As expected, the DBFSF4 with a twisted-linkage exhibits higher triplet energy than DBFSF2 and can be used in blue and green phosphorescent OLEDs. Electrophosphorescent devices with DBFSF2 and DBFSF4 as hosts were fabricated. Besides the good current efficiencies of 22.2 cd A(-1) for blue and 64.4 cd A(-1) for green, low efficiency roll-off has also been achieved for both devices.

A Hybrid Functional Study on Perovskite-Based Compounds CsPb1-αZnαI3-ßXß (X = Cl or Br).

Inorganic perovskites have attracted a great deal of attention because of their stability. Unfortunately, a weak optical response and the toxicity of lead are hampering their development. Motivated by these facts, we focus herein on the perovskite-based doped series CsPb1-αZnαI3-ßXß (X = Cl or Br). The geometric structures and the electronic and optical properties of CsPb1-αZnαI3-ßXß (X = Cl or Br) are investigated systematically by hybrid functional theory. Analysis of the electronic properties indicates that Zn/Cl/Br mono-doping and co-doping efficiently tune bandgaps. Moreover, we find that the ability to obtain electrons for CsPb0.625Zn0.375I2Cl is superior to the abilities of the others, which implies a stronger electron transition. In addition, CsPb0.625Zn0.375I2Cl and CsPb0.625Zn0.375I2Br show stronger visible-light responses in the range of 467-780 nm. Both CsPb0.625Zn0.375I2Cl and CsPb0.625Zn0.375I2Br are hence good choices for photovoltaic applications. Furthermore, the physically accessible region is also explored herein. These findings shed new light on the design of highly efficient and low-lead perovskite-based optoelectronic materials.

Targeted delivery of PARP inhibitors to neuronal mitochondria via biomimetic engineered nanosystems in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is known to activate poly (ADP-ribose) polymerase (PARP-1), which leads to pronounced negative effects on mitochondrial DNA (mt-DNA) repair and function. Notably, PARP inhibitors are reported to be beneficial in experimental models of TBI. A targeting strategy for the delivery of neuronal mitochondria-specific PARP inhibitors could result in a greater neuroprotective effect and be a safer approach for TBI treatment. In the present study, we developed the PARP inhibitor olaparib (Ola) as a model drug and devised red blood cell (RBC)-coated nanostructured lipid carriers (RBCNLCs) co-modified with C3 and SS31 peptide (C3/SS31-RBCNLCs) for brain neuronal mitochondria-targeting. Our results indicated that biomimetic nanosystems have the physical and chemical properties of the NLCs, as well as the biological properties of RBC. A high concentration of Ola delivered into brain mitochondria by C3/SS31-RBCNLCs-Ola effectively improved mitochondrial function and prevented neuronal cell death caused by excessive activation of injury-induced mitochondrial PARP (mt-PARP) in vitro and in vivo. Taken together, the results of this study support the preclinical feasibility of developing highly effective nano-drugs as part of precision medicine for TBI. STATEMENT OF SIGNIFICANCE: TBI-induced neuronal mitochondria DNA damage activates Poly(ADP-ribose) Polymerase (PARP1) which leads to a pronounced negative effect on mitochondrial DNA repair and mitochondrial function. In recent years, PARP inhibitors showed strong benefits in experimental models of TBI, more importantly PARP inhibitors specially target neuronal mitochondria may play a greater neuroprotective role and may be a safer approach for TBI treatment. Herein, we designed red blood cell (RBC) membrane-coated nanostructure lipid carriers dual-modified with C3 and SS31 (C3/SS31-RBCNLCs) to accomplish these objectives. After encapsulating Olaparib (Ola) as the model PARP inhibitor, the data demonstrated that C3/SS31-RBCNLCs, with brain neuronal mitochondria targeting, can reduce neuronal cell death and improve mitochondrial dysfunction triggered by mitochondrial PARP activation in vitro and in vivo.

Corrigendum to "Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice" [Bioactive materials 6 (2021) 529-542].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.08.017.].

Highly Efficient Quasi-2D Perovskite Light-Emitting Diodes Incorporating a TADF Dendrimer as an Exciton-Retrieving Additive.

Although small organics or polymer additives have been introduced to enhance film formation and radiative recombination of perovskite light-emitting diodes (PeLEDs), the exciton utilization and quantum efficiency need further optimization. Here, we introduce a thermal-activated delayed fluorescence (TADF) dendrimer as an additive to enhance the surface coverage and reduce the trap state of the grain boundary. More importantly, the TADF nature of such an additive can retrieve the exciton dissociated from perovskite or trapped by the grain boundary and then transfer the energy back to emissive perovskite through the Förster energy transfer process. Since the triplets can be reused by reverse intersystem crossing in such a TADF additive, the theoretical exciton utilization is 100%. As a result, the optimized PeLEDs cooperating with a TADF additive achieved a high current efficiency of 39.0 cd A-1 and an ultrabright luminescence of 18,000 cd m-2, which are almost 5 times higher than those of the control device without an additive. Moreover, the device stability monitored by half-lifetime at 1000 cd m-2 enhanced 2 times after introducing the TADF dendrimer as an additive. The parent dendrimer without a TADF feature was also synthesized as an additive to explore the mechanism action, which found that 54% enhancement of device efficiency can be attributed to defect passivating, while 46% was assigned to retrieved energy. This research first demonstrates that the TADF dendrimer is a promising exciton-retrieving additive for enhancing the performance of PeLEDs by passivating defect, filling up grain boundary, and retrieving leakage exciton.

Macrophage membrane-coated nanocarriers Co-Modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer's disease mice.

Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species (ROS) is an early event of sporadic Alzheimer's disease (AD), and considered to be a key pathologic factor in the progression of AD. The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD. A safe and effective drug delivery system (DDS) which is able to cross the blood-brain barrier (BBB) and target neuronal mitochondria is necessary. Recently, bioactive materials-based DDS has been widely investigated for the treatment of AD. Herein, we developed macrophage (MA) membrane-coated solid lipid nanoparticles (SLNs) by attaching rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules to the surface of MA membrane (RVG/TPP-MASLNs) for functional antioxidant delivery to neuronal mitochondria. According to the results, MA membranes camouflaged the SLNs from being eliminated by RES-rich organs by inheriting the immunological characteristics of macrophages. The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons. After entering the neurons in CNS, TPP further lead the DDS to mitochondria driven by electric charge. The Genistein (GS)- encapsulated DDS (RVG/TPP-MASLNs-GS) exhibited the most favorable effects on reliveing AD symptoms in vitro and in vivo by the synergies gained from the combination of MA membranes, RVG29 and TPP. These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems.

T807-modified human serum albumin biomimetic nanoparticles for targeted drug delivery across the blood-brain barrier.

Novel biocompatible Human Serum Albumin (HSA) nanoparticles composed of membrane of erythrocytes (ETm)-coated and DSPE-PEG3400-T807 segments have been designed for sustained drug delivery across the blood-brain barrier (BBB). The nanoparticles have developed by induced albumin self-assembly with glutathione as reducing agent. The chemical, physical and biocompatible properties of the T807/ETm-HSA nanoparticles have been characterised by hydrogen nuclear magnetic resonance, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, transmission electron microscopy, dynamic light scattering and confocal laser scanning microscopy techniques. The unique targeting properties of the nanoparticles after fabrication with the brain-targeted ligand T807 was demonstrated by their attaching to brain cells as well as their enhanced transport ability to cross the BBB. In a further demonstration of their ability to target brain cells, in vivo living imaging revealed that T807/ETm-HSA nanoparticles accumulated in the mice brain after intravenous injection. The surface modification of ETm/HSA nanoparticles with the brain-targeted T807 demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified ETm-coated HSA nanoparticles to penetrate the brain.

A multifunctional gelatine-quaternary ammonium copolymer: An efficient material for reducing dye emission in leather tanning process by superior anionic dye adsorption.

Leather wastewater is one of the most polluting industrial emissions. The efficiency of wastewater remediation is limited by its complex composition. Herein, a novel strategy for designing modified gelatine with higher degree of quaternization (MG-2) is presented. The higher degree of quaternization allows sufficient adsorption of dyes in the tanning process. It is an in situ, environmentally friendly, and innovative strategy to limit dye emissions and can circumvent the subsequent waste management. Dyes such as Direct Purple N and Acid Black 24 could be adsorbed completely within 5 min by the MG-2 film formed from MG-2 solution. In addition, a remarkable efficiency in removing Acid Red 73, Golden Orange G, and Acid Orange II (>96.1% removal rates) was achieved within 30 min. The adsorption equilibrium data suggested that the adsorption capacity was positively correlated to the concentration of MG-2. When Acid Orange II and MG-2 were used in the industrial re-tanning process, the residual dye concentration in wastewater was only 23.1 mg L-1, indicating that MG-2 is a promising re-tanning agent for adsorbing dyes in the leather tanning process.

Neuronal mitochondria-targeted delivery of curcumin by biomimetic engineered nanosystems in Alzheimer's disease mice.

Biomimetic nanotechnology represents a promising approach for the delivery of therapeutic agents for the treatment of complex diseases. Recently, neuronal mitochondria have been proposed to serve as a promising therapeutic target for sporadic Alzheimer's disease (AD). However, the efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge due to the complicated physiological and pathological environment. Herein, we devised and tested a strategy for functional antioxidant delivery to neuronal mitochondria by loading antioxidants into red blood cell (RBC) membrane-camouflaged human serum albumin nanoparticles bearing T807 and triphenylphosphine (TPP) molecules attached to the RBC membrane surface (T807/TPP-RBC-NPs). With the advantage of the suitable physicochemical properties of the nanoparticles and the unique biological functions of the RBC membrane, the T807/TPP-RBC-NPs are stabilized and promote sustained drug release, providing improved biocompatibility and long-term circulation. Under the synergistic effects of T807 and TPP, T807/TPP-RBC-NPs can not only penetrate the blood-brain barrier (BBB) but also target nerve cells and further localize in the mitochondria. After encapsulating curcumin (CUR) as the model antioxidant, the research data demonstrated that CUR-loaded T807/TPP-RBC-NPs can relieve AD symptoms by mitigating mitochondrial oxidative stress and suppressing neuronal death both in vitro and in vivo. In conclusion, the intravenous neuronal mitochondria-targeted biomimetic engineered delivery nanosystems provides an effective drug delivery platform for brain diseases. STATEMENT OF SIGNIFICANCE: The efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge for drug delivery due to the complicated physiological and pathological environment. To address this need, various types of nanovessels have been fabricated using a variety of materials in the last few decades. However, problems with the synthetic materials still exist and even cause toxicology issues. New findings in nanomedicine are promoting the development of biomaterials. Herein, we designed a red blood cell (RBC) membrane-coated human serum albumin nanoparticle dual-modified with T807 and TPP (T807/TPP-RBC-NPs) to accomplish these objectives. After encapsulating curcumin as the model drug, the research data demonstrated that the intravenous neuronal mitochondria-targeted biomimetic engineered delivery nanosystems are a promising therapeutic candidate for mitochondrial dysfunction in Alzheimer's disease (AD).

Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating.

Phase-separated films of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be utilized to tailor drug release from coated pellets. In the present study, the effects of HPC levels and the pH, type, ionic strength and osmolarity of the media on the release profiles of soluble metoprolol succinates from the EC/HPC-coated pellets were investigated, and the differences in drug-release kinetics in multiple media were further elucidated through the HPC leaching and swelling kinetics of the pellets, morphology (SEM) and water uptake of the free films and the interaction between the coating polymers and the media compositions. Interestingly, the drug release rate from the pellets in different media was not in agreement with the drug solubility which have a positive correlation with the drug dissolution rate based on Noyes⁻Whitney equation law. In particular, the drug release rate in acetate buffer at pH 4.5 was faster than that in other media despite the solubility of drug was relatively lower, regardless of the HPC levels. It may be attributed to the mutual effect between the EC and acetate buffer, which improved the permeability of the film. In contrast, the release of drug in HCl solution was dependent on the HPC levels. Increasing the levels of HPC increased the effects of hydrogen ions on the polymer of HPC, which resulted in a lower viscosity and strength of the gel, forming the larger size of pores in polymer films, thus increasing the drug diffused from the coating film. Further findings in phosphate buffer showed a reduction in the drug release compared to that in other media, which was only sensitive to the osmolarity rather than the HPC level and pH of the buffer. Additionally, a mathematical theory was used to better explain and understand the experimentally measured different drug release patterns. In summary, the study revealed that the effects of the media overcompensated that of the drug solubility to some extent for controlled-release of the coating polymers, and the drug release mechanism in multiple media depend on EC and HPC rather than on HPC alone, which may have a potential to facilitate the optimization of ideally film-coated formulations.

New optical method for the determination of ß-galactosidase and α-fetoprotein based on oxidase-like activity of fluorescein.

Fluorescein has been found as an efficient visible-light-induced oxidase mimic and its catalytic performance is group-dependent. Herein, a facile colorimetric strategy for ß-galactosidase (ß-gal) was developed using fluorescein di ß-D-galactopyranoside (FDG) as a probe based on the analyte induced change in oxidase mimicking activity of fluorescein derivatives. FDG doesn't possess any visible-light-induced oxidase activity and can generate fluorescein and fluorescein mono ß-D-galactopyranoside (FMG) in the presence of ß-gal. The in situ generated fluorescein and FMG possess high oxidase-like activities under visible-light illumination and could catalyze the oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) upon short irradiation by light-emitting diode (LED) lamp. Thus, the ß-gal activity can be selectively detected in linear range from 0.10 to 12.9 µg mL-1 with a limit of detection (LOD) of 0.04 µg mL-1. We further integrated with the visual detection of α-fetoprotein antigen (AFP) based on the corresponding colorimetric signal induced by ß-gal-linked colorimetric immunoassay, a LOD of 0.08 ng mL-1 could be achieved. Significantly, our proposed assay provides a facile sensing platform based on the change in enzyme mimicking activity induced by analytes. In addition, this optical method works without complex synthesis procedure and efficiently avoids participation of unstable H2O2 as an oxidant. Therefore, the present work not only shows the excellent assay performance in ß-gal and tumor biomarker detection, but also opens up a new avenue for its application in practical optical sensing.

Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex.

BACKGROUND: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status. METHODS: In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized. RESULTS: The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration. CONCLUSION: In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.

Dual-Modified Novel Biomimetic Nanocarriers Improve Targeting and Therapeutic Efficacy in Glioma.

Glioma is a fatal disease with limited treatment options and very short survival. Although chemotherapy is one of the most important strategies in glioma treatment, it remains extremely clinically challenging largely due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Thus, the development of nanoparticles with both BBB and BBTB penetrability, as well as glioma-targeting feature, is extremely important for the therapy of glioma. New findings in nanomedicine are promoting the development of novel biomaterials. Herein, we designed a red blood cell membrane-coated solid lipid nanoparticle (RBCSLN)-based nanocarrier dual-modified with T7 and NGR peptide (T7/NGR-RBCSLNs) to accomplish these objectives. As a new kind of biomimetic nanovessels, RBCSLNs preserve the complex biological functions of natural cell membranes while possessing physicochemical properties that are needed for efficient drug delivery. T7 is a ligand of transferrin receptors with seven peptides that is able to circumvent the BBB and target to glioma. NGR is a peptide ligand of CD13 that is overexpressed during angiogenesis, representing an excellent glioma-homing property. After encapsulating vinca alkaloid vincristine as the model drug, T7/NGR-RBCSLNs exhibited the most favorable antiglioma effects in vitro and in vivo by combining the dual-targeting delivery effect. The results demonstrate that dual-modified biomimetic nanoparticles provide a potential method to improve drug delivery to the brain, hence increasing glioma therapy efficacy.

Systematic Development of Self-Nanoemulsifying Liquisolid Tablets to Improve the Dissolution and Oral Bioavailability of an Oily Drug, Vitamin K1.

The purpose of this study is to improve the dissolution and oral bioavailability of an oily drug, vitamin K1 (VK1) by combination of self-nanoemulsifying and liquisolid technologies. The optimal liquid self-nanoemulsifying drug delivery systems (SNEDDS) formulation including VK1 (oil), mixture of soybean lecithin and glycocholic acid (surfactant) and Transcutol HP (cosurfactant) was obtained according to ternary phase diagrams and a central composite design. Based on compatibility, adsorption capacity and dissolution profile, liquid SNEDDS was then solidified on Fujicalin® to form solid SNEDDS by liquisolid technology and compressed directly with excipients into self-nanoemulsifying liquisolid (SNE-L) tablets. Uniform nano-emulsion suspension was formed rapidly when the SNE-L tablets disintegrated in dissolution media and higher drug dissolution was observed compared with the conventional tablets. The results of pharmacokinetic study in beagle dogs showed that the mean Cmax and the area under the curve of SNE-L tablets were remarkably higher than those of conventional tablets, which were consistent with the results of the in vitro dissolution. The relative bioavailability of SNE-L tablets and conventional tablets was approximately 200%. In conclusion, this combination method showed promise to improve the dissolution and oral bioavailability of oily drug vitamin K1.