Effect of phosphorus and sodium acetate on lipid accumulation from Ankistrodesmus sp. IFRPD 1061 in an open pond.

Ankistrodesmus sp, has been comprehensively studied for their potential in the production of biodiesel due to their biomass productivity and high lipid content. This study examined the biomass productivity, and concentration, lipid productivity, and concentration, and lipid contents of Ankistrodesmus sp. IFRPD 1061 under several phosphorus concentrations. The optimum conditions were attained at 0.12 g/L KH2PO4. The highest lipid content reached to 35.950 ± 4.253% (w/w) in 22 days cultivation. An open pond cultivation system was used with the addition of 10 mM sodium acetate on every fourth day (0, 4, 8 and 12) of cultivation and KH2PO4 on twelfth day of cultivation. The obtained biomass productivity and concentration, lipid productivity and concentration and lipid content were 0.709 ± 0.027 g/L, 48.304 ± 1.894 mg/L/day, 0.214 ± 0.004 g/L 14.550 ± 0.215 mg/L/day and 30.154 ± 1.627% (w/w) in 14 days of cultivation, respectively. The results exhibited that addition of 10 mM sodium acetate and KH2PO4 may enhance lipid accumulation within algae cells in an open pond cultivation system.

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses.

Osteoporosis (OP), is a systemic bone disorder associated with low bone mass and bone tissue corrosion. Worsening of the disease condition leads to bone delicacy and fracture. Various drugs are available for the treatment of OP, however they have limitations including poor solubility, bioavailability and toxicity. Herein, Raloxifene-loaded polymeric nanoparticles (RLX-PNPs) were developed and investigated for the treatment of OP with possible solutions to the above mentioned problems. RLX-PNPs were prepared by modified ionic gelation method followed by determining their particle properties. FTIR, DSC and PXRD analysis of the RLX-PNPs were performed to check chemical interaction, thermal behavior and crystallinity, respectively. In-vitro release profile of RLX-PNPs was checked in lab setting, whereas its pharmacokinetics was investigated in Sprague-Dawley rats, in-vivo. Finally, the treatment potential of RLX-PNPs was analyzed in OP induced animal model. The optimized PNPs formulation indicated 134.5 nm particle size, +24.4 mV charge and 91.73% % EE. TEM analysis showed spherical and uniform sized particles with no interactions observed in FTIR analysis. In-vitro release of RLX from RLX-PNPs showed more sustained release behavior as compared to RLX-suspension. Moreover, pharmacokinetic investigations showed a significantly enhanced bioavailability of the RLX-PNPs as well as reduced serum levels of alkaline phosphatase and calcium in OP induced rats when compared with RLX-Suspension after oral administration. Findings of this study suggested that the developed RLX-PNPs have the potential to treat OP due to sustained release and improved bioavailability of the incorporated drug.

Cytotoxic Activity of Phytoconstituents Isolated from Monotheca buxifolia against Hepatocellular Carcinoma Cell Line HepG2: In Vitro and Molecular Docking Studies.

Natural products and conventional chemotherapeutic drugs are believed to enhance anticancer treatment efficacy while lowering toxicity. The current study investigates the cytotoxic and apoptogenic effects of Monotheca buxifolia bioactive compounds on HepG2 cell lines. MTT assay was used to assess the effect on the viability of HepG2 cells. Morphological changes were investigated. Annexin-V-FITC/PI was used to demonstrate apoptotic activity. A molecular dynamics simulation study was carried out to investigate the compound binding pattern in the active site of the PPRAδ protein. MTT and annexin V-FITC/PI assays revealed that the isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells. The IC50 value for lauric acid was 56.46 ± 1.20 µg/mL, 31.94 ± 1.03 µg/mL for oleanolic acid, and 83.80 ± 2.18 µg/mL for bis(2-ethylhexyl) phthalate. Apoptosis was observed in 29.5, 52.1 and 22.4% of HepG2 cells treated with lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate, respectively, after 24 h of treatment. Morphological assays and Hoechst staining microscopy revealed that the treatment caused morphological changes in the cell membrane and nuclear condensation. The high fluctuation indicates that various interactions were highly potent and widely adopted, and vice versa. Oleanolic acid displayed high residue fluctuation, remaining stable in the active site of the PPRAδ protein and involved in various interactions while remaining locally fluctuating in the binding sites of the other two compounds. These findings concluded that lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate have a significant apoptogenic effect against HepG2 cells in inducing apoptosis. Our findings suggest that these bioactive compounds could be used as adjuvant therapies.

Phenotypic Analysis, Molecular Characterization, and Antibiogram of Caries-Causing Bacteria Isolated from Dental Patients.

Dental caries is a biofilm-mediated, sugar-driven, multifactorial, dynamic disease that results in the phasic demineralization and remineralization of dental hard tissues. Despite scientific advances in cariology, dental caries remains a severe global concern. The aim of this study was to determine the optimization of microbial and molecular techniques for the detection of cariogenic pathogens in dental caries patients, the prevalence of cariogenic bacteria on the basis of socioeconomic, climatological, and hygienic factors, and in vitro evaluation of the antimicrobial activity of selected synthetic antibiotics and herbal extracts. In this study, oral samples were collected from 900 patients for bacterial strain screening on a biochemical and molecular basis. Plant extracts, such as ginger, garlic, neem, tulsi, amla, and aloe vera, were used to check the antimicrobial activity against the isolated strains. Synthetic antimicrobial agents, such as penicillin, amoxicillin, erythromycin, clindamycin, metronidazole, doxycycline, ceftazidime, levofloxacin, and ciprofloxacin, were also used to access the antimicrobial activity. Among 900 patients, 63% were males and 37% were females, patients aged between 36 and 58 (45.7%) years were prone to disease, and the most common symptom was toothache (61%). For oral diseases, 21% used herbs, 36% used antibiotics, and 48% were self-medicated, owing to sweets consumption (60.66%) and fizzy drinks and fast food (51.56%). Staphylococcus mutans (29.11%) and Streptococcus sobrinus (28.11%) were found as the most abundant strains. Seven bacterial strains were successfully screened and predicted to be closely related to genera S. sobrinus, S. mutans, Actinomyces naeslundii, Lactobacillus acidophilus, Eubacterium nodatum, Propionibacterium acidifaciens, and Treponema Pallidum. Among plant extracts, the maximum zone of inhibition was recorded by ginger (22.36 mm) and amla (20.01 mm), while among synthetic antibiotics, ciprofloxacin and levofloxacin were most effective against all microbes. This study concluded that phyto extracts of ginger and amla were considered suitable alternatives to synthetic antibiotics to treat dental diseases.

Exploring the Therapeutic Properties of Alga-Based Silver Nanoparticles: Anticancer, Antibacterial, and Free Radical Scavenging Capabilities.

The current study was designed to evaluate the antioxidant, anticancer and antimicrobial activities of silver nanoparticles (AgNPs) biosynthesized by Spirulina platensis extract. The biosynthesized silver nanoparticles were characterized using Fourier transform infrared (FT-IR) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. The antioxidant activity of the biosynthesized AgNPs were determined via DPPH radical scavenging assay while its anticancer activity was determined using the MTT assay. The antimicrobial activity of the biosynthesized AgNPs were analyzed by disc diffusion method. Spirulina platensis acts as a reducing and capping agent. The efficacy of silver nanoparticles (AgNPs) in inhibiting the growth of Gram-negative bacteria, specifically Acetobacter, Klebsiella, Proteus vulgaris, and Pseudomonas aeruginosa, was assessed by the utilisation of the diffusion method. The study aimed to evaluate the efficacy of biosynthesized silver nanoparticles (AgNPs) against many strains of Pseudomonas aeruginosa bacteria. The findings of the study revealed that when administered in doses of 50 µl, 75 µl, and 100 µl, the largest observed zone of inhibition corresponded to measurements of 10.5 mm, 14 mm, and 16 mm, respectively. A zone of inhibition with dimensions of 8 mm, 10.5 mm, and 12 mm was detected during testing against Acetobacter at concentrations of 50 µl, 75 µl, and 100 µl, respectively. The findings also indicate that there is a positive correlation between the concentration of AgNP and the DPPH scavenging ability of silver nanoparticles. The percentage of inhibition observed at concentrations of 500 µg/ml, 400 µg/ml, 300 µg/ml, 200 µg/ml, and 100 µg/ml were recorded as 80±1.98, 61±1.98, 52±1.5, 42±1.99, and 36±1.97, respectively. In addition, it was observed that the silver nanoparticles exhibited the greatest antioxidant activity at a concentration of 500 g/ml, with a measured value of 80.89±1.99. The IC-50 values, representing the inhibitory concentration required to achieve 50 % inhibition, were found to be 8.16, 19.15, 30.14, 41.13, and 63.11 at inhibition levels of 36±1.97, 42±1.99, 52±1.5, 61±1.98, and 80±1.98, respectively.

Current pandemic COVID-19 vaccine strategies and development: a comprehensive review

The coronavirus disease-19 pandemic with the characteristics of asymptomatic condition, long incubation period and poor treatment has influenced the entire globe. Coronaviruses are important emergent pathogens, specifically, the recently emerged sever acute respiratory syndrome coronavirus 2, the causative virus of the current COVID-19 pandemic. To mitigate the virus and curtail the infection risk, vaccines are the most hopeful solution. The protein structure and genome sequence of SARS-CoV-2 were processed and provided in record time; providing feasibility to the development of COVID-19 vaccines. In an unprecedented scientific and technological effort, vaccines against SARS-CoV-2 have been developed in less than one year. This review addresses the approaches adopted for SARS-CoV-2 vaccine development and the effectiveness of the currently approved vaccines(AU)

La pandemia de COVID-19, con sus características de condición asintomática, largo periodo de incubación y escaso tratamiento, ha tenido un impacto global. Los coronavirus son importantes patógenos emergentes, específicamente, el coronavirus del síndrome respiratorio agudo severo 2 descubierto recientemente, virus causal de la actual pandemia de COVID-19. Para mitigar el virus y reducir el riesgo de infección, las vacunas son la solución más esperanzadora. La estructura de la proteína y la secuencia del genoma del SARS-CoV-2 se procesaron y proporcionaron en un tiempo récord, lo que ha permitido el desarrollo de las vacunas contra el COVID-19. En un esfuerzo científico y tecnológico sin precedentes, se han desarrollado vacunas contra el SARS-CoV-2 en menos de un año. Esta revisión aborda los enfoques adoptados para el desarrollo de la vacuna contra el SARS-CoV-2 y la eficacia de las vacunas actualmente aprobadas(AU)

Formulation Development and Ex-Vivo Permeability of Curcumin Hydrogels under the Influence of Natural Chemical Enhancers.

BACKGROUND: The aim of the present research was to formulate and evaluate curcumin hydrogel and to investigate the potential of natural essential oils as permeation enhancers. METHODS: Curcumin 2% w/w hydrogel containing various concentrations of eucalyptus oil, aloe vera oil and clove oil was developed using carboxy methyl cellulose (CMC) as a gelling agent. Differential scanning calorimetry and Fourier Transform infrared spectroscopy were used to evaluate the compatibility between the drug and the excipients. In order to assess the efficacy of the formulation; rheological properties, skin irritation studies, in vitro release, ex vivo permeation and retention studies were conducted. RESULTS: DSC and FTIR suggest no in-compatibility between curcumin and excipients. Studies proved that addition of suitable natural permeation enhancers to the hydrogels improved the in vitro release and ex vivo permeation and retention of curcumin. From the various natural essential oils, the aloe vera oil at a concentration of 3% w/w had the greatest effect on the permeability rate and skin retention of the Curcumin and produces the highest enhancement ratio amongst all the concentrations of essential oils examined. CONCLUSION: Aloe vera oil enhances the permeation of curcumin across the skin by altering the complex structure of the stratum corneum without itself undergoing any change. The developed curcumin hydrogels along with natural essential oils may present an effective choice regarding skin infection/wound healing.

Cisplatin and oleanolic acid Co-loaded pH-sensitive CaCO3 nanoparticles for synergistic chemotherapy.

Despite being one of the most potent anticancer agents, cisplatin (CDDP) clinical usage is limited owing to the acquired resistance and severe adverse effects including nephrotoxicity. The current work has offered a unique approach by designing a pH-sensitive calcium carbonate drug delivery system for CDDP and oleanolic acid (OA) co-delivery, with an enhanced tumor efficacy and reduced unwanted effects. Micro emulsion method was employed to generate calcium carbonate cores (CDDP encapsulated) followed by lipid coating along with the OA loading resulting in the generation of lipid-coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs). In vitro biological assays confirmed the synergistic apoptotic effect of CDDP and OA against HepG2 cells. It was further verified in vivo through the tumor-bearing nude mice model where NPs exhibited enhanced satisfactory antitumor efficacy in contrast to free drug solutions. In vivo pharmacokinetic study demonstrated that a remarkable long circulation time with a constant therapeutic concentration for both drugs could be achieved via this drug delivery system. In addition, the in vivo imaging study revealed that DiR-loaded NPs were concentrated more in tumors for a longer period of time as compared to other peritoneal tissues in tumor bearing mice, demonstrating the site specificity of the delivery system. On the other hand, hematoxylin and eosin (H&E) staining of Kunming mice kidney tissue sections revealed that OA greatly reduced CDDP induced nephrotoxicity in the formulation. Overall, these results confirmed that our pH-sensitive dual loaded drug delivery system offers a handy direction for effective and safer combination chemotherapy.

Residential extremely low frequency magnetic fields and skin cancer.

OBJECTIVE: Photoinduced radical reactions have a fundamental role in skin cancer induced by ultraviolet radiation, and changes in radical reactions have also been proposed as a mechanism for the putative carcinogenic effects of extremely low frequency (ELF) magnetic fields (MFs). We assessed the association of melanoma and squamous cell carcinoma with residential MF exposure. METHODS: All cohort members had lived in buildings with indoor transformer stations (TSs) during the period from 1971 to 2016. MF exposure was assessed based on apartment location. Out of the 225 492 individuals, 8617 (149 291 person-years of follow-up) living in apartments next to TSs were considered as exposed, while individuals living on higher floors of the same buildings were considered as referents. Associations between MF exposure and skin cancers were examined using Cox proportional hazard models. RESULTS: The HR for MF exposure ≥6 month was 1.05 (95% CI 0.72 to 1.53) for melanoma and 0.94 (95% CI 0.55 to 1.61) for squamous cell carcinoma. Analysis of the age at the start of residence showed an elevated HR (2.55, 95% CI 1.15 to 5.69) for melanoma among those who lived in the apartments when they were less than 15 years old. This finding was based on seven exposed cases. CONCLUSIONS: The results of this study suggested an association between childhood ELF MF exposure and adult melanoma. This is in agreement with previous findings suggesting that the carcinogenic effects of ELF MFs may be associated particularly with childhood exposure.

Cellulase Addition and Pre-hydrolysis Effect of High Solid Fed-Batch Simultaneous Saccharification and Ethanol Fermentation from a Combined Pretreated Oil Palm Trunk.

In the current study, alkaline hydrogen peroxide pretreated oil palm trunk fibers were subjected to ethanol production via simultaneous saccharification and fermentation (SSF). The effect of high substrate loading, enzyme and substrate feeding strategy, and influence of a pre-hydrolysis step in SSF was studied to scale up ethanol production. In the enzyme feeding strategy, the addition of an enzyme at the start of fed-batch SSF significantly (p < 0.05) increased ethanol concentration to 51.05 g/L, ethanol productivity (QP ) to 0.61 g/L·h, and ethanol yield (Y P/S) to 0.31 g/g, with a theoretical ethanol yield of 60.65%. Furthermore, the initial velocity of the enzyme (V 0) in the first 8 h was 2.27 (g/h) with a glucose concentration of 18.17 g/L. On the other hand, the substrate feeding strategy and pre-hydrolysis simultaneous saccharification and fermentation (PSSF) process were studied in a 1 L fermenter. PSSF in fed batch with 10 and 20% (w/v) significantly improved enzyme hydrolysis, circumvent the problems of high viscosity, reduced overall fermentation time, and gave the highest ethanol concentration of 51.66 g/L, ethanol productivity (QP ) of 0.72 g/L·h, ethanol yield (Y P/S) of 0.31 g/g, and theoretical ethanol yield of 60.66%. In addition, PSSF with 10 and 20% significantly increased the initial velocity of the enzyme (V 0) to 4.64 and 4.40 (g/h) and glucose concentration to 37.14 and 35.27 g/L, respectively. This result indicated that ethanol production by PSSF along with substrate feeding could enhance ethanol production efficiently.

Unethical Leadership and Employee Extra-Role Behavior in Information Technology Sector: A Moderated Mediation Analysis.

During the COVID-19 pandemic, enterprises were obliged to employ social media and digital tools to complete ordinary work. The pandemic has created a series of complexities and challenges, which have hampered harmonic contact between leaders and followers. The indirect relationship between unethical leadership and extra-role behavior (EXB) via psychological empowerment (PYE) is investigated in this study. We also look into the role of perceived organizational support (POS) as a moderator in the link between unethical leadership and PYE, as well as the indirect link between unethical leadership and EXB. Data were obtained from 258 supervisor-employee dyads from various small- and mid-sized information technology (IT) enterprises using time lag data. Unethical leadership has an impact on employee psychological empowerment as well as EXB. The findings of this study indicated that POS also mitigated the negative consequences of unethical leadership on employee psychological empowerment. Similarly, the role of psychological empowerment as a mediator in the link between unethical leadership and employee EXB is influenced by POS. This study will also benefit researchers and practitioners interested in human resource practices in the IT industry.

Macrophage targeting with the novel carbopol-based miltefosine-loaded transfersomal gel for the treatment of cutaneous leishmaniasis: in vitro and in vivo analyses.

OBJECTIVE: The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) via efficient targeting of leishmania infected macrophages. METHODS: Miltefosine-loaded transfersomes (HePCT) were prepared by ethanol injection method followed by their incorporation into carbopol gel to form HePCTG. The prepared HePCT were assessed for physicochemical properties including mean particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, and deformability. Similarly, HePCTG was evaluated for physiochemical and rheological attributes. The in vitro release, skin permeation, skin irritation, anti-leishmanial activity, and in vivo efficacy in BALB/c mice against infected macrophages were also performed for HePCT. RESULTS: The optimized HePCT displayed a particle size of 168 nm with entrapment efficiency of 92%. HePCTG showed suitable viscosity, pH, and sustained release of the incorporated drug. Furthermore, HePCT and HePCTG demonstrated higher skin permeation than drug solution. The results of macrophage uptake study indicated improved drug intake by passive diffusion. The lower half maximal inhibitory concentration value, selectivity index and higher 50% cytotoxic concentration  value of HePCT compared to that of HePC solution demonstrated the improved anti-leishmanial efficacy and non-toxicity of the formulation. This was further confirmed by the notable reduction in parasite load and lesion size observed in in vivo anti-leishmanial study. CONCLUSION: It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.

A cohort study on adult hematological malignancies and brain tumors in relation to magnetic fields from indoor transformer stations.

Extremely low frequency (ELF) magnetic fields (MF) have been classified as possibly carcinogenic. This classification was mainly based on studies indicating increased risk of leukemia in children living near power lines. Increased risks of adult hematological malignancies and brain tumors have also been reported, but the results are mixed. We assessed incidence of adult hematological malignancies and brain tumors associated with residential MF exposure. All cohort members had lived in buildings with indoor transformer stations (TS). MF exposure was assessed based on apartment location. Out of the 256,372 individuals, 9,636 (165,000 person-years of follow-up) living in apartments next to TSs were considered as exposed. Associations between MF exposure and neoplasms were examined using Cox proportional hazard models. The hazard ratio (HR) for MF exposure ≥ 1 month was below one for most hematological neoplasms (HR for any hematological neoplasm: 0.75; 95% CI: 0.54-1.03), and decreased with increasing duration of exposure (HR for exposure ≥ 10 years: 0.47; 95% CI: 0.22-0.99). However, the HR for acute lymphocytic leukemia (ALL) was 2.86 (95% CI: 1.00-8.15), based on 4 exposed cases; the risk increased with duration of exposure (HR for exposure ≥3 years: 3.61; 95% CI: 1.05-12.4) and was particularly associated with childhood exposure (2 exposed cases, HR for exposure during the first two years of life: 11.5; 95% CI: 1.92-68.9). The HR for meningioma was 0.46 (95% CI: 0.19-1.11), with no evidence of exposure-response gradient with increasing duration of exposure. The HR for glioma was 1.47 (95% CI: 0.84-2.57). The hypothesis of a positive association between ELF MFs and adult hematological malignancies was supported only for ALL. The results suggested decreased rather than increased risk of most hematological neoplasms.

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects.

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both in vivo and in vitro. In addition, Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

Registry of Buildings With Transformer Stations as a Basis for Epidemiological Studies on Health Effects of Extremely Low-Frequency Magnetic Fields.

Buildings with indoor transformer stations may serve as a basis for improved epidemiological studies on the health effects of extremely low-frequency magnetic fields (ELF MFs). Previous studies have shown that ELF MF exposure can be adequately assessed based on the fact that MF levels are high in apartments directly above transformers. In this paper, we describe the creation of a registry of Finnish residential buildings with built-in transformer stations and discuss its usability in epidemiological studies. Information obtained from electric utilities and building blueprints were used to identify 677 buildings in which an apartment was located above or adjacent to a transformer station. All apartments in these buildings were classified into exposure categories based on their location in relation to the transformer. Residential histories of these buildings were obtained from the Population Register Centre. Out of the 287,668 individuals who have resided in the buildings, 9,126 of them have resided in an apartment located directly above a transformer station. All information was collected without contacting residents, thus avoiding selection bias. The registry can be linked with data from high-quality nationwide registries to confirm or challenge the reported associations of ELF MF exposure and diseases such as cancer, miscarriage, and Alzheimer's disease. Bioelectromagnetics. 2020;41:34-40 © 2019 Bioelectromagnetics Society.

Pharyngeal Obturator Prosthetic Rehabilitation of Velopharyngeal Insufficiency.

Congenital or acquired defects of soft palate cause physical, functional and psychological disabilities. Surgical closure or prosthetic rehabilitation are the two treatment modalities. If surgery is contraindicated, prosthetic rehabilitation is the alternative treatment option. Pharyngeal obturator prosthesis provides adequate closure of the velopharyngeal insufficiency. In this case report, a young patient is treated for velopharyngeal insufficiency with pharyngeal obturator as the patient had refused to undergo surgical closure. The prosthesis was successfully fabricated and was evaluated for proper functioning. It improved speech, deglutition and psychological well-being of the patient.

Biocompatible co-loading vehicles for delivering both nanoplatin cores and siRNA to treat hepatocellular carcinoma.

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies. Herein, a biocompatible nanocarrier was designed in the study to deliver a chemotherapeutical agent CDDP and Bmi-1 siRNA to kill cancer cells and silence drug resistance related gene simultaneously. Calciumphosphate (CaP) was applied to coat both nanoplatin cores and siRNA as a shell for the purpose of delivering cargos to the cytosol of the tumor cells. Nanoplatin and siRNA co-loaded CaP nanoparticles (NPSC) enhanced cell uptake of CDDP and showed elevated drug accumulation in tumor. NPSC achieved considerable anti-cancer efficacy and counter-regulated drug tolerance, therefore, warranted a further investigation as a novel therapeutic nanosystem to improve cancer therapy.

Co-delivery of Bmi1 small interfering RNA with ursolic acid by folate receptor-targeted cationic liposomes enhances anti-tumor activity of ursolic acid in vitro and in vivo.

Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.

Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity.

Background: Cisplatin (CDDP), a widely used chemotherapeutic agent against hepatocellular carcinoma (HCC), faces severe resistance and hepatotoxicity problems which can be alleviated through combination therapy. Purpose: The objective of this study was to develop a pH-dependent calcium carbonate nano-delivery system for the combination therapy of CDDP with oleanolic acid (OA). Methods: A microemulsion method was employed to generate lipid coated cisplatin/oleanolic acid calcium carbonate nanoparticles (CDDP/OA-LCC NPs), and the loading concentration of CDDP and OA was measured by atomic absorption spectroscopy and HPLC respectively.Transmission electron microscopy (TEM) was used to examine the nanoparticles morphology while its pH dependent release characteristics were investigated through in vitro release study. Cellular uptake was examined through a fluorescence microscopy. Apoptotic assays and western blot analysis were conducted to explore the synergistic apoptotic effect of OA on CDDP against HCC cells. The hepatoprotective of OA for CDDP was evaluated through H&E staining. Results: TEM analysis revealed nanoparticles spherical shape with an average particle size of 206±15 nm, and the overall entrapment efficiency was 63.70%±3.9%. In vitro drug release study confirmed the pH-dependent property of the formulation, with the maximum CDDP release of 70%±4.6% at pH 5.5, in contrast to 28%±4.1% CDDP release at pH 7.4. Annexin V-FITC/PI assay and cell cycle analysis confirmed that CDDP and OA synergistically promoted greater HepG2 cells apoptosis for the CDDP/OA-LCC NPs as compared to their individual free drug solutions and NPs-treated groups. Western blot analysis also proved that CDDP/OA-LCC NPs induced the apoptosis by enhancing the proapoptotic protein expressions through downregulating P13K/AKT/mTOR pathway and upregulating p53 proapoptotic pathway. OA helped CDDP to overcome the resistance by downregulating the expression of proteins like XIAP, Bcl-2 via NF-κB pathway. OA also significantly alleviated CDDP-induced hepatotoxicity as evident from the decreased alanine transaminase, aspartate transaminase levels and histochemical evaluation. The possible mechanism may be related to the Nrf-2 induction via its antioxidant mechanism to maintain the redox balance and reduction in CYP2E1 activity which can lead to ROS-mediated oxidative stress. Conclusion: These results suggest that CDDP/OA-LCC NPs have promising applications for co-delivering CDDP and OA to synergize their anti-tumor activity against HCC and to utilize OA's protective effect against CDDP-induced hepatotoxicity.

CXCR4-Receptor-Targeted Liposomes for the Treatment of Peritoneal Fibrosis.

Peritoneal fibrosis (PF) is a common complication of long-term peritoneal dialysis (PD). It is considered as the main reason for dialysis inadequacy and PD withdrawal. Transforming growth factor beta (TGF-ß) regulates the expression of stromal cell-derived factor 1 (SDF-1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4) on human peritoneal mesothelial cells (HPMCs), resulting in an increased migratory potential of HPMCs and extracellular matrix (ECM) deposition in the scar tissue and eventually fibrosis. Because SDF-1α/CXCR4 activation has a vital role in the pathogenesis of PF, codelivery of a CXCR4-receptor targeting agent with an antifibrotic agent in a single nanocarrier can be a promising strategy for treating PF. Here, for the first time, AMD3100 (AMD), a CXCR4-receptor antagonist, was coformulated with sulfotanshinone IIA sodium (STS IIA) into a liposome (STS-AMD-Lips) to develop a CXCR4 receptor targeting form of combination therapy for PF. CXCR4 targeting increased the ability of liposomes to target fibrotic peritoneal mesothelial cells overexpressing CXCR4 and facilitated the ability of STS IIA treatment at the fibrotic site. The liposome had an average diameter of 103 nm with encapsulated efficiencies of above 50%. The in vivo studies confirmed the reversal of PD solution-induced epithelial-to-mesenchymal transition by STS-AMD-Lips in HPMCs. The in vivo studies also revealed the precise biodistribution of the liposomes to peritoneum. Significant reduction of the morphological lesions and decreased level of ECM proteins were observed in rats treated with STS-AMD-Lips, proving that the liposomal nanocarrier has excellent ability to reverse PF. It has been concluded that the STS-AMD-Lips exhibit specific peritoneal targeting ability and could be used to improve STS-AMD combination delivery for the treatment of PF.