Manganese-derived biomaterials for tumor diagnosis and therapy.

Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.

Development and validation of a flexible DNA extraction (PAN) method for liquid biopsy of multiple sample types.

BACKGROUND: Liquid biopsy is gaining increasing popularity in cancer screening and diagnosis. However, there is no relatively mature DNA isolation method or commercial kit available that is compatible with different LB sample types. This study developed a PAN-sample DNA isolation method (PAN method) for liquid biopsy samples. METHODS: The PAN method has two key steps, including biosample-specific pretreatments for various LB sample types and high concentration guanidine thiocyanate buffer for lysis and denaturation procedure. Subsequently, the performance of PAN method was validated by a series of molecular analyses. RESULTS: The PAN method was used to isolate DNA from multiple sample types related to LB, including plasma, serum, saliva, nasopharyngeal swab, and stool. All purified DNA products showed good quality and high quantity. Comparison of KRAS mutation analysis using DNA purified using PAN method versus QIAamp methods showed similar efficiency. Epstein-Barr virus DNA was detected via Q-PCR using DNA purified from serum, plasma, nasopharyngeal swab, and saliva samples collected from nasopharyngeal carcinoma patients. Similarly, methylation sequencing of swab and saliva samples revealed good coverage of target region and high methylation of HLA-DPB1 gene. Finally, 16S rDNA gene sequencing of saliva, swab, and stool samples successfully defines the relative abundance of microbial communities. CONCLUSIONS: This study developed and validated a PAN-sample DNA isolation method that can be used for different LB samples, which can be applied to molecular epidemiological research and other areas.

Clinical effectiveness of Er,Cr:YSGG lasers in non-surgical treatment of chronic periodontitis: a meta-analysis of randomized controlled trials.

The meta-analysis aimed to systematically evaluate all the available pieces of evidence concerning the clinical effectiveness of Er,Cr:YSGG lasers (erbium, chromium, yttrium scandium gallium garnet laser) in the non-surgical treatment of patients with chronic periodontitis, and provide guidance for clinicians about the application of Er,Cr:YSGG lasers during the process of non-surgical periodontal treatments. The meta-analysis was conducted with data extracted from 16 randomized controlled clinical trials (RCTs) that compare Er,Cr:YSGG lasers adjunct/substitute to scaling and root planing (SRP) with SRP alone for the treatment of chronic periodontitis published in English or Chinese from January 2000 to January 2020. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were counted for probing depth (PD) reduction, clinical attachment level (CAL) gain, and visual analogue scale (VAS) score. Heterogeneity of each study was evaluated with the Q test. The publication bias was measured using Begg's adjusted rank correlation test. Sixteen RCTs with 606 patients were included in the meta-analysis. There were statistically significant differences between Er,Cr:YSGG lasers adjunct/substitute to SRP and SRP alone in the PD reduction at 1-month follow-up (WMD = ­ 0.35, 95% CI [- 0.63, ­ 0.07], P = 0.013), 3-month follow-up (WMD = - 0.342, 95% CI [- 0.552, - 0.132], P = 0.001), CAL gain at 3-month follow-up (WMD = - 0.17, 95% CI [- 0.31, 0.03], P = 0.017), and VAS score (WMD = - 2.395, 95% CI [- 3.327, - 1.464], P = 0.000) immediately after treatment. There were no significant differences of PD reduction and CAL change at 6-month follow-up. The present meta-analysis indicated that Er,Cr:YSGG lasers provided additional effectiveness in PD reduction and CAL gain at short-term follow-ups and there was less pain compared with SRP alone.

Seramator thermalis gen. nov., sp. nov., a novel cellulose- and xylan-degrading member of the family Dysgonamonadaceae isolated from a hot spring.

Two anaerobic bacteria, designated strains SYSU GA16112T and SYSU GA16107, were isolated from a hot spring in Tengchong County, Yunnan Province, south-west PR China. Phylogenetic analyses based on 16S rRNA gene sequences showed that strains SYSU GA16112T and SYSU GA16107 belong to the family Dysgonamonadaceae. Cells of strains SYSU GA16112T and SYSU GA16107 were Gram-stain-negative, rod-shaped and non-motile. The major fatty acids (>10 %) of strains SYSU GA16112T and SYSU GA16107 were identified as anteiso-C15 : 0 and anteiso-C17 : 0 3OH. The polar lipid profile of strain SYSU GA16112T was found to consist of phosphatidylethanolamine, two unidentified aminophospholipids, two unidentified phosphoglycolipids, two unidentified aminolipids and one unidentified polar lipid, while that of strain SYSU GA16107 consisted of phosphatidylethanolamine, two unidentified polar lipids, three unidentified aminophospholipids, two unidentified phosphoglycolipids and one unidentified aminolipid. The genomic DNA G+C contents of strains SYSU GA16112T and SYSU GA16107 were determined to be 41.90 and 41.89 %, respectively, and the average nucleotide identity value between them was 99.99 %. Based on their morphological and physiological properties, and results of phylogenetic analyses, strains SYSU GA16112T and SYSU GA16107 are considered to represent a novel species of a novel genus, for which the name Seramator thermalis gen. nov., sp. nov. (type strain SYSU GA16112T=CGMCC 1.5281T=KCTC 15753T) is proposed.

Additive Manufacturing of Nanocellulose Aerogels with Structure-Oriented Thermal, Mechanical, and Biological Properties.

Additive manufacturing (AM) is widely recognized as a versatile tool for achieving complex geometries and customized functionalities in designed materials. However, the challenge lies in selecting an appropriate AM method that simultaneously realizes desired microstructures and macroscopic geometrical designs in a single sample. This study presents a direct ink writing method for 3D printing intricate, high-fidelity macroscopic cellulose aerogel forms. The resulting aerogels exhibit tunable anisotropic mechanical and thermal characteristics by incorporating fibers of different length scales into the hydrogel inks. The alignment of nanofibers significantly enhances mechanical strength and thermal resistance, leading to higher thermal conductivities in the longitudinal direction (65 mW m-1 K-1) compared to the transverse direction (24 mW m-1 K-1). Moreover, the rehydration of printed cellulose aerogels for biomedical applications preserves their high surface area (≈300 m2 g-1) while significantly improving mechanical properties in the transverse direction. These printed cellulose aerogels demonstrate excellent cellular viability (>90% for NIH/3T3 fibroblasts) and exhibit robust antibacterial activity through in situ-grown silver nanoparticles.

Acoustic triggered nanobomb for US imaging guided sonodynamic therapy and activating antitumor immunity.

We fabricated an ultrasound activated 'nanobomb' as a noninvasive and targeted physical therapeutic strategy for sonodynamic therapy and priming cancer immunotherapy. This 'nanobomb' was rationally designed via the encapsulation of indocyanine green (ICG) and perfluoropentane (PFP) into cRGD peptide-functionalized nano-liposome. The resulting Lip-ICG-PFP-cRGD nanoparticle linked with cRGD peptide could actively targeted ID8 and TC-1 cells and elicits ROS-mediated apoptosis after triggered by low-intensity focused ultrasound (LIFU). Moreover, the phase change of PFP (from droplets to microbubbles) under LIFU irradiation can produce a large number of microbubbles, which act as intra-tumoral bomber and can detonate explode tumor cells by acoustic cavitation effect. Instant necrosis of tumor cells further induces the release of biologically active damage-associated molecular patterns (DAMPs) to facilitate antitumor immunity. More important, the 'nanobomb' in combination with anti-PD-1checkpoint blockade therapy can significantly improve the antitumor efficacy in a subcutaneous model. In addition, the liposomes may also be used as an imaging probe for ultrasound (US) imaging after being irradiated with LIFU. In summary, the US imaging-guided, LIFU activated ROS production and explosion 'nanobomb' might significantly improve the antitumor efficacy and overcome drug resistance through combination of SDT and immunotherapy, we believe that this is a promising approach for targeted therapy of solid tumor including ovarian cancer.

Two-Pronged Anti-Tumor Therapy by a New Polymer-Paclitaxel Conjugate Micelle with an Anti-Multidrug Resistance Effect.

Introduction: Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Thus, reversing tumor MDR has become a research focus of medical scientists. Methods: Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug resistance as a carrier to overcome MDR and improve the anti-tumor effect of PTX. Results: The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of PTX to H22 subcutaneous tumor-bearing mice. Conclusion: This work proves that the reduction-sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy.

Calcium phosphate (CaP) is the principal inorganic constituent of bone and teeth in vertebrates and has various applications in biomedical areas. Among various types of CaPs, amorphous calcium phosphate (ACP) is considered to have superior bioactivity and biodegradability. With regard to the instability of ACP, the phosphorus-containing molecules are usually adopted to solve this issue, but the specific roles of the molecules in the formation of nano-sized CaP have not been clearly clarified yet. Herein, alendronate, cyclophosphamide, zoledronate, and foscarnet are selected as the model molecules, and theoretical calculations were performed to elucidate the interaction between calcium ions and different model molecules. Subsequently, CaPs were prepared with the addition of the phosphorus-containing molecules. It is found that cyclophosphamide has limited influence on the generation of CaPs due to their weak interaction. During the co-precipitation process of Ca2+ and PO4 3-, the competitive relation among alendronate, zoledronate, and foscarnet plays critical roles in the produced inorganic-organic complex. Moreover, the biocompatibility of CaPs was also systematically evaluated. The DFT calculation provides a convincing strategy for predicting the structure of CaPs with various additives. This work is promising for designing CaP-based multifunctional drug delivery systems and tissue engineering materials.

Blood-clotting model and simulation analysis of polyvinyl alcohol-chitosan composite hemostatic materials.

The blood-clotting performance and characteristics of hemostatic materials are critical for their development and actual application. Based on the theory of porous media and characteristics of a non-Newtonian fluid, this study proposed an adsorption factor to characterize the porosity generation and blood coagulation process of hemostatic materials. On this basis, we constructed a physical model of blood coagulation in a porous medium integrated with the power-law fluid model to study the proposed poly(vinyl alcohol)-chitosan (PVA-CS) composite hemostatic material. Moreover, we simulated the dynamic blood flow process and blood coagulation process in the PVA-CS hemostatic material by introducing the physical model. The simulation results show that the blood begins to coagulate, which affects the porosity and permeability of the blood-containing area, resulting in changing the porosity after blood flowed into the hemostatic material. The porosity, permeability, and blood flow rate will approach zero until the generated blood coagulation entirely blocked the porous medium. Besides, simulation can provide the pressure and velocity distribution varying in the coagulation process of hemostatic materials. The temperature will also influence the hemostatic performance of the PVA-CS material. In all, the proposed simulation method enabled the coagulation mechanism of PVA-CS to be revealed from the perspective of blood flow in porous media combined with the adsorption factor.

Anisotropic cellulose nanofiber/chitosan aerogel with thermal management and oil absorption properties.

Attributed to low cost, renewable, and high availability, cellulose-based aerogels are desirable materials for various applications. However, mechanical robustness and functionalization remain huge challenges. Herein, we synthesized a recoverable, anisotropic cellulose nanofiber (CNF) / chitosan (CS) aerogel via directional freeze casting and chemical cross-link process. The chitosan was performed as strength polymers to prohibits the shrinkage and retains the structural stability of 3D cellulose nanofiber skeleton, endowing the composite aerogel with satisfactory deformation recovery ability (without loss under 60 % stress cycled 100 times). The CNF/CS composite aerogel has ultralow density (∼8.4 mg/cm3), high temperature-invariant (above 300 °C) and high porosity (98 %). The CNF/CS aerogel demonstrates anisotropic thermal insulation properties with low thermal conductivity (28 mWm-1 K-1 in rational direction and 36 mW m-1 K-1 in the axial direction). Moreover, the composite aerogel (water contact angle ∼148°) exhibited outstanding oil/water selectivity and high absorption capacity (82-253 g/g) for various oils and organic solvents. Therefore, the multifunctional CNF/CS composite aerogels are potential materials for thermal management and oil absorption applications.

A class of water-soluble Fe(III) coordination complexes as T1-weighted MRI contrast agents.

Iron-based coordination complexes are showing increasing potential to be alternatives for T1-weighted magnetic resonance imaging (MRI) and contribute to the safety of gadolinium-based compounds. In this work, three water-soluble iron-based complexes constructed using catechol ligands exhibiting T1-weighted MRI contrast behavior are described. The longitudinal relaxivity (r1) increase from 0.88 to 1.43 mM-1 s-1 mainly depends on the sizes and the number of water molecules in the second and outer spheres around the discrete complexes.

Microbially Catalyzed Biomaterials for Bone Regeneration.

Bone is a complex mineralized tissue composed of various organic (proteins, cells) and inorganic (hydroxyapatite, calcium carbonate) substances with micro/nanoscale structures. To improve interfacial bioactivity of bone-implanted biomaterials, extensive efforts are being made to fabricate favorable biointerface via surface modification. Inspired by microbially catalyzed mineralization, a novel concept to biologically synthesize the micro/nanostructures on bioceramics, microbial-assisted catalysis, is presented. It involves three processes: bacterial adhesion on biomaterials, production of CO3 2- assisted by bacteria, and nucleation and growth of CaCO3 nanocrystals on the surface of bioceramics. The microbially catalyzed biominerals exhibit relatively uniform micro/nanostructures on the surface of both 2D and 3D α-CaSiO3 bioceramics. The topographic and chemical cues of the grown micro/nanostructures present excellent in vitro and in vivo bone-forming bioactivity. The underlying mechanism is closely related to the activation of multiple biological processes associated with bone regeneration. The study offers a microbially catalytic concept and strategy of fabricating micro/nanostructured biomaterials for tissue regeneration.

Polydopamine-based nanoplatform for photothermal ablation with long-term immune activation against melanoma and its recurrence.

The high risk of tumor recurrence presents a big challenge in melanoma therapy. Photothermal therapy (PTT) has merged as a powerful weapon against tumor in recent years, which produces tumor-associated antigens (TAA) and recruits dendritic cells (DCs) to tumor sites through immunogenic cell death (ICD) for immune activation. However, due to the lack of activation signals of DCs, the immune effect induced by PTT is not sufficient to inhibit the recurrence and proliferation of tumor. To efficiently cooperate PTT and immunotherapy to circumvent tumor recurrence, here we constructed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs to elicit robust photothermal ablation and antitumor immune responses. Cationized polydopamine coated with hyaluronic acid (HA) shell was proven an efficient photothermal agent that increased the surface temperature of tumor by 16 °C and induced ICD. CpG ODNs effectively induced maturation of DCs by elevating the expression of co-stimulating markers. PTT combined with CpG ODNs achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells in melanoma-bearing mice model compared with PTT or CpG ODNs alone. Furthermore, in a tumor recurrence model, photothermal-immune combination therapy increased the infiltration of CTLs in distant tumor compared with PTT or CpG ODNs alone. The combination therapy overcame insufficient immunity at distant tumor caused by PTT alone and relieved immunosuppression microenvironment of the tumor. Hence, the PDA based core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma. STATEMENT OF SIGNIFICANCE: In order to solve the insufficient immunity induced by photothermal therapy (PTT), CpG ODNs were utilized to enhance the weak immune response mediated by PTT through inducing DCs maturation. Hence, we designed a polydopamine (PDA) based core-shell nanoplatform loading CpG ODNs followed by hyaluronic acid named PPP/CpG/HA to elicit robust photothermal ablation and antitumor immune responses. CpG ODNs were delivered to the tumor site through the targeting effect of the HA shell. The core-shell nanoplatform achieved a remarkable synergistic treatment effect in the maturation of DCs and activation of T cells, thereby overcoming insufficient immunity at distant tumor caused by PTT alone. The core-shell nanoplatform presents a potent photo-immunotherapy against proliferation and recurrence of melanoma.

pH-Triggered Copper-Free Click Reaction-Mediated Micelle Aggregation for Enhanced Tumor Retention and Elevated Immuno-Chemotherapy against Melanoma.

Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno-chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-ß (TGF-ß)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.

Cellulose from sources to nanocellulose and an overview of synthesis and properties of nanocellulose/zinc oxide nanocomposite materials.

Recently, environmental and ecological concerns are increasing due to the usage of petroleum-based products so the synthesis of ultra-fine chemicals and functional materials from natural resources is drawing a tremendous level of attention. Nanocellulose, a unique and promising natural material extracted from native cellulose, may prove to be most ecofriendly materials that are technically and economically feasible in modern times, minimizing the pollution generation. Nanocellulose has gained tremendous attention for its use in various applications, due to its excellent special surface chemistry, physical properties, and remarkable biological properties (biodegradability, biocompatibility, and non-toxicity). Various types of nanocellulose, viz. cellulose nanofibrils (CNFs), cellulose nanocrystals (CNCs), and bacterial nanocellulose (BNC), are deeply introduced and compared in this work in terms of sources, production, structures and properties. The metal and metal oxides especially zinc oxide nanoparticles (ZnO-NPs) are broadly used in various fields due to the diversity of functional properties such as antimicrobial and ultraviolet (UV) properties. Thus, the advancement of nanocellulose and zinc oxide nanoparticles (ZnO-NPs)-based composites materials are summarized in this article in terms of the preparation methods and remarkable properties with the help of recent knowledge and significant findings (especially from the past six years reports). The nanocellulose materials complement zinc oxide nanoparticles, where they impart their functional properties to the nanoparticle composites. As a result hybrid nanocomposite containing nanocellulose/zinc oxide composite has shown excellent mechanical, UV barrier, and antibacterial properties. The nanocellulose based hybrid nanomaterials have huge potential applications in the area of food packaging, biopharmaceuticals, biomedical, and cosmetics. Thus the functional composite materials containing nanocellulose and zinc oxide will determine the potential biomedical application for nanocellulose.

Isolation of Clostridium from Yunnan-Tibet hot springs and description of Clostridium thermarum sp. nov. with lignocellulosic ethanol production.

Lignocellulose is considered a major source of renewable energy that serve as an alternative to the fossil fuels. Members of the genus Clostridium are some of the many microorganisms that have the ability to degrade lignocellulose efficiently to sugar, which can be further converted to biofuel. In this study, we isolated twelve Clostridium strains from hot spring samples of Yunnan and Tibet, of which isolates SYSU GA15002T and SYSU GA17076 showed low 16S rRNA gene sequence identity profiles to any of the validly named Clostridium strains (<94.0%). Studies using a polyphasic taxonomy approach concluded that the two isolates represent one novel species of the genus Clostridium, for which we propose the name Clostridium thermarum sp. nov., with SYSU GA15002T as the type strain of the species. Isolate SYSU GA15002T has an optimum growth temperature at 45°C. Fermentation of the substrates cellobiose, cellulose, xylan and untreated straw powder by this strain results in the production of ethanol, along with acetate and formate. The complete pathways for the conversion of cellulose and xylan to ethanol is also predicted from the genome of isolate SYSU GA15002T, which revealed a single step conversion of lignocellulosic biomass through consolidated bioprocessing. This paper is a comprehensive study encompassing isolation, polyphasic taxonomy, lignocellulose biodegradation and the genomic information of Clostridium in Yunnan-Tibet hot springs.

Formulation, Pharmacokinetic Evaluation and Cytotoxicity of an Enhanced- penetration Paclitaxel Nanosuspension.

BACKGROUND: Improving poorly soluble drugs into druggability was a major problem faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the solubility, chemical stability and reducing the use of additives, which provided a new approach for the development and application of the insoluble drugs formulation. Paclitaxel (PTX) is a well-known BCS class IV drug with poor solubility and permeability. Also, many studies have proved that paclitaxel is a substrate of the membrane-bound drug efflux pump P-glycoprotein (P-gp), therefore it often shows limited efficacy against the resistant tumors and oral absorption or uptake. OBJECTIVE: To manufacture an enhanced-penetration PTX nanosuspension (PTX-Nanos), and evaluate the physicochemical property, pharmacokinetics and tissue distribution in vivo and cytotoxic effect in vitro. METHODS: PTX-Nanos were prepared by microprecipitation-high pressure homogenization, with a good biocompatibility amphiphilic block copolymer poly(L-phenylalanine)-b-poly(L-aspartic acid) (PPA-PAA) as stabilizer. RESULTS: The PTX-Nanos had a sustained-dissolution manner and could effectively reduce plasma peak concentration and extend plasma circulating time as compared to PTX injection, markedly passively targeting the MPS-related organs, such as liver and spleen. This unique property might enhance treatment of cancer in these tissues and reduce the side effects in other normal tissues. Moreover, the hybrid stabilizers could enhance penetration of PTX in PTX-Nanos to multidrug resistance cells. CONCLUSION: To sum up, our results showed that the optimal formula could improve the solubility of PTX and the stability of the product. The PTX-Nanos developed in this research would be a promising delivery platform in cancer treatment.

A straightforward method for measuring the range of apparent density of microplastics.

Density of microplastics has been regarded as the primary property that affect the distribution and bioavailability of microplastics in the water column. For measuring the density of microplastis, we developed a simple and rapid method based on density gradient solutions. In this study, we tested four solvents to make the density gradient solutions, i.e., ethanol (0.8 g/cm3), ultrapure water (1.0 g/cm3), saturated NaI (1.8 g/cm3) and ZnCl2 (1.8 g/cm3). Density of microplastics was measured via observing the float or sink status in the density gradient solutions. We found that density gradient solutions made from ZnCl2 had a larger uncertainty in measuring density than that from NaI, most likely due to a higher surface tension of ZnCl2 solution. Solutions made from ethanol, ultrapure water, and NaI showed consistent density results with listed densities of commercial products, indicating that these density gradient solutions were suitable for measuring microplastics with a density range of 0.8-1.8 g/cm3.

Formulation and characterization of biocompatible and stable I.V. itraconazole nanosuspensions stabilized by a new stabilizer polyethylene glycol-poly(ß-Benzyl-l-aspartate) (PEG-PBLA).

Amphiphilic block copolymers, PEG-PBLA with different molecular weights, were synthesized and used as new stabilizers for Itraconazole nannosuspensions (ITZ-PBLA-Nanos). ITZ-PBLA-Nanos were prepared by the microprecipitation-high pressure homogenization method, and the particle size and zeta potential were measured using a ZetaSizer Nano-ZS90. Morphology and crystallinity were studied using TEM, DSC and powder X-ray. The effect of the PEG-to-PBLA ratio, and the drug-to-stabilizer ratio were investigated to obtain the optimal formulation. It was found that the optimal length of hydrophobic block was 25 BLA-NCA molecules and the optimal ratio of drug/stabilizer was 1:1, where the resulted average particle size of ITZ-PBLA-Nanos was 262.1±7.13nm with a PDI value of 0.163±0.011. The images of TEM suggest that ITZ-PBLA-Nanos were rectangular in shape. ITZ existed as crystals in the nanoparticles as suggested by the DSC and XRD results. Compared with the crude drug suspensions, the dissolution rate of ITZ nanocrystals, was significantly increased and was similar to Sporanox® injection. The ITZ-PBLA-Nanos also demonstrated better dilution stability and storage stability compared with ITZ-F68-Nanos. The particle size of ITZ-PBLA-Nanos did not change significantly after incubated in rat plasma for 24h which is a good attribute for I.V. administration. Acute toxicity tests showed that ITZ-PBLA-Nanos has the highest LD50 compared with ITZ-F68-Nanos and Sporanox® injection. ITZ-PBLA-Nanos also showed stronger inhibiting effect on the growth of Candida albicans compared with Sporanox® injection. Therefore, PEG-PBLA has a promising potential as a biocompatible stabilizer for ITZ nanosuspensions and potentially for other nanosuspensions as well.

Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.