Fine particulate matter air pollution and the mortality of children under five: a multilevel analysis of the Ethiopian Demographic and Health Survey of 2016.

Background: Every year, polluted air is costing the globe 543,000 deaths of children under five. The particulate matter below 2.5 µm diameter (PM2.5) is a part of air pollution that has adverse effects on children's health. In Ethiopia, the effect of ambient PM2.5 is least explored. This study aimed to assess the association between PM2.5 and under-five mortality in Ethiopia. Methods: The study used the data from the Ethiopian Demographic Health Surveys conducted in 2016, collected between January 18 and June 27. All children under five who had data on child mortality and location coordinates were included in the study. Exposure to ambient PM2.5 concentration was a satellite-based estimate by the Atmospheric Composition Analysis Group at Washington and Dalhousie University, in the United States and Canada, respectively. Annual mean pollution levels and mortality datasets were matched by children's geographical location and dates of birth, death, and interview. The relationship between ambient PM2.5 and under-five mortality was determined by a multilevel multivariable logistic regression on R software. The statistical analyses were two-sided at a 95% confidence interval. Results: The study addressed 10,452 children with the proportion of under-five mortality being 5.4% (95% CI 5.0-6.8%). The estimated lifetime annual mean exposure of ambient total PM2.5 was 20.1 ± 3.3 µgm-3. A 10-unit increase in the lifetime annual mean ambient total PM2.5 was associated with 2.29 [95% CI 1.44, 3.65] times more odds of under-five mortality after adjusting for other variables. Conclusion: Children under five are exposed to higher levels of ambient PM2.5 concentration, exceeding the limit set by the World Health Organization. Ambient PM2.5 is significantly associated with under-five mortality, adjusting for other variables. Strong measures need to be taken to reduce air pollution.

Nonfatal Occupational Injuries Among Artisanal and Small-scale Gold Mining Workers in Ethiopia.

Background: Artisanal and Small-scale Gold Mining (ASGM) is widely practiced in Ethiopia. Injuries are among the public health concerns in the mining sector. This study aimed to assess the prevalence of nonfatal occupational injuries and associated factors among workers in ASGM in Ethiopia. Methods: A cross-sectional study design was employed from April to June 2020. A total of 403 participants were selected with a simple random sampling technique. A structured questionnaire was utilized for the data collection. Descriptive statistics were used to characterize the information and binary logistic regression was applied to test the association. Predictor variables with P-value < .05 with an Odds ratio of 95% CI in multivariable analysis were considered as associated factors. Results: A total of 403 participants were interviewed with a response rate of 95.5%. The prevalence of nonfatal occupational injury was 25.1% in the past 12 months. About one-third of the injuries, 32 (31.7%), were on the upper extremity and feet, 18 (17.8%). Symptoms of mercury toxicity (AOR: 2.39, 95% CI [1.27-4.52]), 1 to 4 years of work experience (AOR: 4.50, 95% CI [1.57-12.9]), full work shift (AOR: 6.06, 95% CI [1.97-18.7]), and job in the task of mining activities (AOR: 4.83, 95% CI [1.48-15.7]) were associated with the injury. Conclusion: A substantially high prevalence of injuries was observed. Work-related factors were found to be significantly associated with the occurrence of injury. The government body, mining sector, and workers are advised to apply interventions focusing on the improvement of working conditions and safety practices to minimize injury.

The spatial and temporal variation of fine particulate matter pollution in Ethiopia: Data from the Atmospheric Composition Analysis Group (1998-2019).

BACKGROUND: Evidence suggests ambient fine particulate matter (PM2.5) is a risk factor for cardiovascular diseases, lung cancer morbidity and mortality, and all-cause mortality. Countries that implement strong policies are able to reduce ambient PM2.5 concentration. In Ethiopia, however, PM2.5 monitoring stations, laboratory technicians, and equipment are staggeringly limited. In this study, the spatial and temporal variation of PM2.5 in Ethiopia was assessed. METHODS: Satellite-based PM2.5 estimates, from the year 1998 to 2019, by Atmospheric Composition Analysis Group (ACAG) at a spatial resolution of 0.01° X 0.01° was used. The annual mean PM2.5 concentration for all administrative regions and zones in Ethiopia was extracted. The average mean from the twenty-two years was also calculated. The trend of PM2.5 concentration was graphed and quantitatively calculated using the Mann-Kendall test. The slope of the change over time was estimated using the Theil-Sen slope. At the zonal administration level, for the average annual mean, spatial dependency using univariate Global Moran's I and clustering and outlier tests using Anselin Local Moran's were performed. RESULTS: The country's average annual mean PM2.5 concentration was 17 µgm-3. The Afar region had the highest concentration, 27.9 µgm-3. The Mann-Kendall S was positive and significant at p<0.001. The spatial distribution of satellite-based ambient PM2.5 concentration was non-random. Significant highest value clustering of ambient total PM2.5 concentration exists in the Afar, Eastern Tigray, and Eastern and Southeastern Amhara while the significant lowest value dispersing was observed in the Southern Oromia and Somali region. CONCLUSION: At the national and regional levels, the annual mean ambient PM2.5 concentration is beyond the World Health Organization (WHO)-recommended level. The ambient PM2.5 concentration distribution is spatially dependent and significantly clustered in space. Installation of additional ground-based PM2.5 monitoring devices, particularly in regions where PM2.5 concentration is higher, is recommended. Validating satellite-based PM2.5 data with ground-based measurements in the country is also advised.

PAMAM Dendritic Nanoparticle-Incorporated Hydrogel to Enhance the Immunogenic Cell Death and Immune Response of Immunochemotherapy.

The efficiency of chemotherapy is frequently affected by its multidrug resistance, immune suppression, and severe side effects. Its combination with immunotherapy to reverse immune suppression and enhance immunogenic cell death (ICD) has emerged as a new strategy to overcome the aforementioned issues. Herein, we construct a pH-responsive PAMAM dendritic nanocarrier-incorporated hydrogel for the co-delivery of immunochemotherapeutic drugs. The stepwise conjugation of moieties and drug load was confirmed by various techniques. In vitro experimental results demonstrated that PAMAM dendritic nanoparticles loaded with a combination of drugs exhibited spherical nanosized particles, facilitated the sustained release of drugs, enhanced cellular uptake, mitigated cell viability, and induced apoptosis. The incorporation of PAB-DOX/IND nanoparticles into thermosensitive hydrogels also revealed the formation of a gel state at a physiological temperature and further a robust sustained release of drugs at the tumor microenvironment. Local injection of this formulation into HeLa cell-grafted mice significantly suppressed tumor growth, induced immunogenic cell death-associated cytokines, reduced cancer cell proliferation, and triggered a CD8+ T-cell-mediated immune response without obvious systemic toxicity, which indicates a synergistic ICD effect and reverse of immunosuppression. Hence, the localized delivery of immunochemotherapeutic drugs by a PAMAM dendritic nanoparticle-incorporated hydrogel could provide a promising strategy to enhance antitumor activity in cancer therapy.

Combination of ovalbumin-coated iron oxide nanoparticles and poly(amidoamine) dendrimer-cisplatin nanocomplex for enhanced anticancer efficacy.

Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR)-based tumor targeted 4.5 generation poly(amidoamine) dendrimer(4.5GDP)-cisplatin (Cis-pt) nanocomplex (NC) (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs were examined via FTIR spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The conjugation of Cis-pt with 4.5GDP was confirmed using carbon NMR spectroscopy. The tumor-specific 4.5GDP-Cis-pt NC provided 45%and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed for the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NPs were biocompatible with different cell lines, even at a high concentration (200 µg mL-1). However, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL-1) significantly increased the cytotoxicity against the cancer cells in a dose-dependent manner with the increasing AC-IO-Ova NPs concentrations. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, AC-IO-Ova NPs might assist the efficiency of anticancer cells, inducing an innate immune response via M1 macrophage polarization. We provide a novel synergistic chemoimmunotherapeutic strategy to enhance the anticancer efficacy of cisplatin via a chemotherapeutic agent 4.5GDP-Cis-pt NC and induce proinflammatory cytokines stimulating innate immunity through AC-IO-Ova NPs against tumors.

Source Apportionment of Fine Organic Particulate Matter (PM2.5) in Central Addis Ababa, Ethiopia.

The development of infrastructure, a rapidly increasing population, and urbanization has resulted in increasing air pollution levels in the African city of Addis Ababa. Prior investigations into air pollution have not yet sufficiently addressed the sources of atmospheric particulate matter. This study aims to identify the major sources of fine particulate matter (PM2.5) and its seasonal contribution in Addis Ababa, Ethiopia. Twenty-four-hour average PM2.5 mass samples were collected every 6th day, from November 2015 through November 2016. Chemical species were measured in samples and source apportionment was conducted using a chemical mass balance (CMB) receptor model that uses particle-phase organic tracer concentrations to estimate source contributions to PM2.5 organic carbon (OC) and the overall PM2.5 mass. Vehicular sources (28%), biomass burning (18.3%), plus soil dust (17.4%) comprise about two-thirds of the PM2.5 mass, followed by sulfate (6.5%). The sources of air pollution vary seasonally, particularly during the main wet season (June-September) and short rain season (February-April): From motor vehicles, (31.0 ± 2.6%) vs. (24.7 ± 1.2%); biomass burning, (21.5 ± 5%) vs. (14 ± 2%); and soil dust, (11 ± 6.4%) vs. (22.7 ± 8.4%), respectively, are amongst the three principal sources of ambient PM2.5 mass in the city. We suggest policy measures focusing on transportation, cleaner fuel or energy, waste management, and increasing awareness on the impact of air pollution on the public's health.

Trends in non-pharmaceutical intervention (NPI) related community practice for the prevention of COVID-19 in Addis Ababa, Ethiopia.

BACKGROUND: The COVID-19 pandemic has affected Ethiopia since March 13, 2020, when the first case was detected in Addis Ababa. Since then, the incidence of cases has continued to increase day by day. As a result, the health sector has recommended universal preventive measures to be practiced by the public. However, studies on adherence to these preventive measures are limited. OBJECTIVE: To monitor the status of preventive practices of the population related to hand washing, physical distancing, and respiratory hygiene practices at selected sites within the city of Addis Ababa. METHODS: Weekly cross-sectional non-participatory observations were done during the period of April-June, 2020. Data was collected using the Open Data Kit (ODK) tool in ten public sites involving eight public facilities targeted for individual observations. Ten individuals were randomly observed at each facility over two days a week at peak hours of public services. WHO operational definitions of the preventive behaviors were adopted for this study. Observations were conducted anonymously at gates or entrances of public facilities and places. RESULTS: A total of 12,056 individual observations with 53% males and 82% in an estimated age range of 18-50 years age group were involved in this study. There was an increase in the practice of respiratory hygiene from 14% in week one to 77% in week 10, while those of hand hygiene and physical distancing changed little over the weeks from their baseline of 24% and 34%, respectively. Overall, respiratory hygiene demonstrated an increased rate of 6% per week, while hand hygiene and physical distancing had less than a 1% change per week, Females and the estimated age group of 18-50 years had practice changes in respiratory hygiene with no difference in hand hygiene and physical distancing practices. Respiratory hygiene took about six weeks to reach a level of 77% from its baseline of 24%, making an increment of about 9% per week. CONCLUSION: The public practice of respiratory hygiene improved threefold whereas hand hygiene and physical distancing revealed no change. Regularly sustained public mobilization and mass education are required to sustain the achievements gained in respiratory hygiene and further hand hygiene and physical distancing.

Fine particulate pollution concentration in Addis Ababa exceeds the WHO guideline value: Results of 3 years of continuous monitoring and health impact assessment.

Real-time monitoring of fine particulate matter (PM2.5) concentrations and assessing the health impact are limited in Ethiopia. The objective of this study is to describe current levels of PM2.5 air pollution in Addis Ababa and examine temporal patterns and to consider the health impact of current PM2.5 exposure levels. METHODS: PM2.5 concentrations were measured using a centrally-located Beta Attenuator Monitor (BAM-1022) for 3 years (1 April 2017 to 31 March 2020), with data downloaded biweekly. Deaths attributable to current PM2.5 concentration levels were estimated using the AirQ+ tool. The daily average was estimated using hourly data. RESULTS: The daily mean (SD) PM2.5 concentration was 42.4 µg/m3 (15.98). Two daily extremes were observed: morning (high) and afternoon (low). Sundays had the lowest PM2.5 concentration, while Mondays to Thursdays saw a continuous increase; Fridays showed the highest concentration. Seasons showed marked variation, with the highest values during the wet season. Concentration spikes reflected periods of intensive fuel combustion. A total of 502 deaths (4.44%) were attributable to current air pollution levels referenced to the 35 µg/m3 WHO interim target annual level and 2,043 (17.7%) at the WHO 10 µg/m3 annual guideline. CONCLUSION: PM2.5 daily levels were 1.7 times higher than the WHO-recommended 24-hour guideline. The current annual mean PM2.5 concentration results in a substantial burden of attributable deaths compared to an annual mean of 10 µg/m3. The high PM2.5 level and its variability across days and seasons calls for citywide interventions to promote clean air.

Assessment of Computer Vision Syndrome and Personal Risk Factors among Employees of Commercial Bank of Ethiopia in Addis Ababa, Ethiopia.

Background: Computer vision syndrome (CVS) is an amalgam of visual symptoms caused by continued use of computers. Worldwide, up to 70 million workers are at risk for computer vision syndrome resulting in reduced productivity at work and reduced quality of life. Bank employees are among the risky workers with unknown magnitude of the syndrome. Therefore, the main aim of this study was to determine the prevalence of CVS and its associated personal factors among employees of Commercial Bank of Ethiopia. Methods: A total of three hundred and fifty-nine bank workers participated in the study between February and March 2018. A self-administered structured questionnaire was used to collect sociodemographic data, CVS symptoms, and its personal factors. Snellen chart tool was used to measure blurred vision. Data entry and analysis were performed via Epi Info™ 7 and Statistical Package for the Social Sciences (SPSS) version 21. Binary logistic regression and multivariable logistic regression were performed to assess the association and control the potential confounders. Result: The prevalence of computer vision syndrome in the last 12 months among the total study subjects, 359 (98% response rate), was 262 (74.6%) (95% confidence interval [CI] = 70.1, 79.5). Risk factors that could not be intervened with were sex (AOR: 1.8; 95% CI (1-3)) and age group (AOR: 3.11; 95% CI (1.2-8)). Causal factors that could be intervened with were use of electronic materials outside work (AOR: 3.11; 95% CI (1.15-8.36). Protective factor that could be intervened with was habit of taking a break (AOR: 0.44; 95% CI (0.3-0.8)). Conclusion and Recommendation. Three-fours of the employees were at risk. Sex, age, habit of taking a break, and use of electronic materials outside work environment were significantly associated with the presence of CVS. Remedial actions need to be considered at individual level.

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery.

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL-1 in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy.

Ibuprofen-Loaded Heparin Modified Thermosensitive Hydrogel for Inhibiting Excessive Inflammation and Promoting Wound Healing.

Hydrogels have been investigated as ideal biomaterials for wound treatment owing to their ability to form a highly moist environment which accelerates cell migration and tissue regeneration for prompt wound healing. They can also be used as a drug carrier for local delivery, and are able to activate immune cells to enhance wound healing. Here, we developed heparin-conjugated poly(N-isopropylacrylamide), an injectable, in situ gel-forming polymer, and evaluated its use in wound healing. Ibuprofen was encapsulated into the hydrogel to help reduce pain and excessive inflammation during healing. In addition to in vitro studies, a BALB/c mice model was used to evaluate its effect on would healing and the secretion of inflammatory mediators. The in vitro assay confirmed that the ibuprofen released from the hydrogel dramatically reduced lipopolysaccharide-induced inflammation by suppressing the production of NO, PGE2 and TNF-α in RAW264.7 macrophages. Moreover, an in vivo wound healing assay was conducted by applying hydrogels to wounds on the backs of mice. The results showed that the ibuprofen-loaded hydrogel improved healing relative to the phosphate buffered saline group. This study indicates that ibuprofen loaded in an injectable hydrogel is a promising candidate for wound healing therapy.

Chemical Characterization and Seasonality of Ambient Particles (PM2.5) in the City Centre of Addis Ababa.

Ambient air pollution is a growing public health concern in major African cities, including Addis Ababa (Ethiopia), where little information is available on fine particulate matter (PM2.5, with aerodynamic diameter <2.5 µm) pollution. This paper aims to characterize annual PM2.5, including bulk composition and seasonal patterns, in Addis Ababa. We collected 24-h PM2.5 samples in the central city every 6 days from November 2015 to November 2016. The mean (±SD) daily PM2.5 concentration was 53.8 (±25.0) µg/m3, with 90% of sampled days exceeding the World Health Organization's guidelines. Principal components were organic matter (OM, 44.5%), elemental carbon (EC, 25.4%), soil dust (13.5%), and SNA (sulfate, nitrate, and ammonium ions, 8.2%). Higher PM2.5 concentrations were observed during the heavy rain season, while crustal dust concentrations ranged from 2.9 to 37.6%, with higher levels during dry months. Meteorological variables, vehicle emissions, biomass fuels, unpaved roads, and construction activity contribute to poor air quality. Compared to the Air Quality Index (AQI), 31% and 36% of observed days were unhealthy for everyone and unhealthy for sensitive groups, respectively. We recommend adopting effective prevention strategies and pursuing research on vehicle emissions, biomass burning, and dust control to curb air pollution in the city.

Fabrication of Core Crosslinked Polymeric Micelles as Nanocarriers for Doxorubicin Delivery: Self-Assembly, In Situ Diselenide Metathesis and Redox-Responsive Drug Release.

Polymeric micelles (PMs) have been used to improve the poor aqueous solubility, slow absorption and non-selective biodistribution of chemotherapeutic agents (CAs), albeit, they suffer from disassembly and premature release of payloads in the bloodstream. To alleviate the thermodynamic instability of PMs, different core crosslinking approaches were employed. Herein, we synthesized the poly(ethylene oxide)-b-poly((2-aminoethyl)diselanyl)ethyl l-aspartamide)-b-polycaprolactone (mPEG-P(LA-DSeDEA)-PCL) copolymer which self-assembled into monodispersed nanoscale, 156.57 ± 4.42 nm, core crosslinked micelles (CCMs) through visible light-induced diselenide metathesis reaction between the pendant selenocystamine moieties. The CCMs demonstrated desirable doxorubicin (DOX)-loading content (7.31%) and encapsulation efficiency (42.73%). Both blank and DOX-loaded CCMs (DOX@CCMs) established appreciable colloidal stability in the presence of bovine serum albumin (BSA). The DOX@CCMs showed redox-responsive drug releasing behavior when treated with 5 and 10 mM reduced glutathione (GSH) and 0.1% H2O2. Unlike the DOX-loaded non-crosslinked micelles (DOX@NCMs) which exhibited initial burst release, DOX@CCMs demonstrated a sustained release profile in vitro where 71.7% of the encapsulated DOX was released within 72 h. In addition, the in vitro fluorescent microscope images and flow cytometry analysis confirmed the efficient cellular internalization of DOX@CCMs. The in vitro cytotoxicity test on HaCaT, MDCK, and HeLa cell lines reiterated the cytocompatibility (≥82% cell viability) of the mPEG-P(LA-DSeDEA)-PCL copolymer and DOX@CCMs selectively inhibit the viabilities of 48.85% of HeLa cells as compared to 15.75% of HaCaT and 7.85% of MDCK cells at a maximum dose of 10 µg/mL. Overall, all these appealing attributes make CCMs desirable as nanocarriers for the delivery and controlled release of DOX in tumor cells.

Biotin-Decorated PAMAM G4.5 Dendrimer Nanoparticles to Enhance the Delivery, Anti-Proliferative, and Apoptotic Effects of Chemotherapeutic Drug in Cancer Cells.

Biotin receptors are overexpressed by various types of solid cancer cells and play a significant role in tumor metabolism, growth, and metastasis. Thus, targeting the biotin receptors on tumor cells may enhance the efficiency and reduce the side-effects of chemotherapy. The aim of this study was to develop a biotin-coupled poly(amido)amine (PAMAM) (PG4.5) dendrimer nanoparticle to enhance the tumor-specific delivery and intracellular uptake of anticancer drugs via receptor-mediated endocytosis. We modified PG4.5 with diethylenetriamine (DETA) followed by biotin via an amide bond and characterized the resulting PG4.5-DETA-biotin nanoparticles by 1H NMR, FTIR, and Raman spectroscopy. Loading and releasing of gemcitabine (GEM) from PG4.5-DETA-biotin were evaluated by UV-Visible spectrophotometry. Cell viability and cellular uptake were examined by MTT assay and flow cytometry to assess the biocompatibility, cellular internalization efficiency and antiproliferative activity of PG4.5-DETA-biotin/GEM. Gemcitabine-loaded PG4.5-DETA-biotin nanoparticles were spherical with a particle size of 81.6 ± 6.08 nm and zeta potential of 0.47 ± 1.25 mV. Maximum drug-loading content and encapsulation efficiency were 10.84 ± 0.16% and 47.01 ± 0.71%, respectively. Nearly 60.54 ± 1.99% and 73.96 ± 1.14% of gemcitabine was released from PG4.5-DETA-biotin/GEM nanoparticles after 48 h at the acidic pH values of 6.5 and 5, respectively. Flow cytometry and fluorescence microscopy of cellular uptake results revealed PG4.5-DETA-biotin/GEM nanoparticles selectively targeted cancer cells in vitro. Cytotoxicity assays demonstrated gemcitabine-loaded PG4.5-DETA-biotin significantly reduced cell viability and induced apoptosis in HeLa cells. Thus, biotin-coupled PG4.5-DETA nanocarrier could provide an effective, targeted drug delivery system and selectively convey gemcitabine into tumor cells.

In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers.

The recent discovery of small interfering RNAs (siRNAs) has opened new avenues for designing personalized treatment options for various diseases. However, the therapeutic application of siRNAs has been confronted with many challenges because of short half-life in circulation, poor membrane penetration, difficulty in escaping from endosomes, and insufficient release into the cytosol. To overcome these challenges, we designed a diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA)-modified polyamidoamine dendrimer generation 4.5 (PDG4.5), and characterized it using 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy (COSY), heteronuclear single-quantum correlation spectroscopy (HSQC), and Fourier transform infrared (FTIR) spectroscopy followed by conjugation with siRNA. The PDG4.5-DETA and PDG4.5-TEPA polyplexes exhibited spherical nanosize, ideal zeta potential, and effective siRNA binding ability, protected the siRNA from nuclease attack, and revealed less cytotoxicity of PDG4.5-DETA and PDG4.5-TEPA in HeLa cells. More importantly, the polyplexes also revealed good cellular internalization and facilitated translocation of the siRNA into the cytosol. Thus, PDG4.5-DETA and PDG4.5-TEPA can act as potential siRNA carriers in future medical and pharmaceutical applications.

Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy.

In a malignant tumor, overexpression of pro-angiogenic factors like vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks characterized by leaky, chaotically organized, immature, thin-walled, and ill-perfused. As a result, hostile tumor environment would be developed and profoundly hinders anti-cancer drug activities and fuels tumor progression. In this study, we develop a strategy of sequential sustain release of anti-angiogenic drug, Bevacizumab (BVZ), and anti-cancer drug, Doxorubicin (DOX), using poly (d, l-Lactide)- Poly (ethylene glycol) -Poly (d, l-Lactide) (PDLLA-PEG-PDLLA) hydrogel as a local delivery system. The release profiles of the drugs from the hydrogel were investigated in vitro which confirmed that relatively rapid release of BVZ (73.56 ±â€¯1.39%) followed by Dox (61.21 ±â€¯0.62%) at pH 6.5 for prolonged period. The in vitro cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. Likeways, the in vitro degradation of the copolymer showed 41.63 ±â€¯2.62% and 73.25 ±â€¯4.36% weight loss within 6 weeks at pH 7.4 and 6.5, respectively. After a single intratumoral injection of the drug-encapsulated hydrogel on Hela xenograft nude, hydrogel co-loaded with BVZ and Dox displayed the highest tumor suppression efficacy for up to 36 days with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drug by hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Encapsulation of gadolinium ferrite nanoparticle in generation 4.5 poly(amidoamine) dendrimer for cancer theranostics applications using low frequency alternating magnetic field.

Iron oxide-based magnetic resonance imaging (MRI) contrast agents have negative contrast limitations in cancer diagnosis. Gadolinium (Gd)-based contrast agents show toxicity. To overcome these limitations, Gd-doped ferrite (Gd:Fe3O4 (GdIO) nanoparticles (NPs) were synthesized as T1-T2 dual-modal contrast agents for MRI-traced drug delivery. A theranostics GdIO encapsulated in a Generation 4.5 PAMAM dendrimer (G4.5-GdIO) was developed by alkaline coprecipitation. The drug-loading efficiency of the NPs was ∼24%. In the presence of a low-frequency alternating magnetic field (LFAMF), a maximum cumulative doxorubicin (DOX) release of ∼77.47% was achieved in a mildly acidic (pH = 5.0) simulated endosomal microenvironment. Relaxometric measurements indicated superior r1 (5.19 mM-1s-1) and r2 (26.13 mM-1s-1) for G4.5-GdIO relative to commercially available Gd-DTPA. Thus, G4.5-GdIO is promising as an alternative noninvasive MRI-traced cancer drug delivery system.

Fabrication of redox-responsive Bi(mPEG-PLGA)-Se2 micelles for doxorubicin delivery.

Stimuli-responsive polymeric nanostructures have emerged as potential drug carriers for cancer therapy. Herein, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se2 from mPEG-PLGA and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. Due to its amphiphilic nature, Bi(mPEG-PLGA)-Se2 self-assembled in to stable micelles in aqueous solution with a hydrodynamic size of 123.9 ±â€¯0.85 nm. The Bi(mPEG-PLGA)-Se2 micelles exhibited DOX-loading content (DLC) of 6.61 wt% and encapsulation efficiency (EE) of 54.9%. The DOX-loaded Bi(mPEG-PLGA)-Se2 micelles released 73.94% and 69.54% of their cargo within 72 h upon treatment with 6 mM GSH and 0.1% H2O2, respectively, at pH 7.4 and 37 °C. The MTT assay results demonstrated that Bi(mPEG-PLGA)-Se2 was devoid of any inherent toxicity and the DOX-loaded micelles showed pronounced antitumor activities against HeLa cells, 44.46% of cells were viable at maximum dose of 7.5 µg/mL. The cellular uptake experiment further confirmed the internalization of DOX-loaded Bi(mPEG-PLGA)-Se2 micelles and endowed redox stimuli triggered drug release in cytosol and nuclei of cancer cells. Overall, the results suggested that the smart, biocompatible Bi(mPEG-PLGA)-Se2 copolymer could serve as potential drug delivery biomaterial for the controlled release of hydrophobic drugs in cancer cells.

Redox-Responsive Heparin-Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity.

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin-chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.

Indoor and Outdoor Air Pollution- related Health Problem in Ethiopia: Review of Related Literature.

BACKGROUND: The health effects of air pollution are generally global problems, but they have, since recently become issues of particular concern for developing countries. This review assessed the situation of air pollution and related health effects in the context of Ethiopia. METHODS: The materials reviewed in this publication are published scientific papers from online search engines, unpublished government reports and academic theses/dissertations. In addition, interview data obtained from authorities and experts involved in the management of air quality were analyzed, interpreted and reported in the article. RESULTS: Review of the few studies conducted in Ethiopia showed that average concentrations of PM2.5 reached as high as 280 µg/m3 for 24-hour measurements (range: 2,417-12,739 µg/m3). Indoor carbon monoxide (CO) levels were universally higher than regulatory limits for the United States and were found to be much higher among households using traditional stoves and solid biomass fuels. The use of traditional stoves and solid biomass fuels was reported in >95% of the households considered. High average levels of NO2 (97 ppb) were reported in a large longitudinal study. The ambient PM10 level was below the WHO guideline values in the majority of the samples. About 50% of the on-road CO samples taken from traffic roads in Addis Ababa were found to be less than the guideline values while the number of motor vehicles in Ethiopia is reported to be increasing by more than 9% per annum. There is a very limited air quality monitoring capacity in the country. The co-ordination between stakeholders in this regard is also inadequate. The limited evidence available on health effects of air pollution indicates that the prevalence of acute respiratory illness among children living in households using crude biomass fuels is significantly higher than the national average figures. CONCLUSION: The limited evidence reviewed and reported in this article indicates high levels of indoor air pollution and trends of worsening outdoor air pollution. This tentative conclusion carries with it the urgent need for more evidence-based research and capacity building in the areas of indoor and outdoor air pollution.