The Lower Mekong Delta Coastal Zone (LMDCZ) is emblematic of the coastal erosion problem facing many tropical deltas. Over the last 3500 years, large river sediment fluxes expanded the delta seaward, ...and waves and currents formed the Ca Mau Peninsula to the southwest. Since the middle of the 20th century, the LMDCZ is affected by various human activities that include reduction of river fluxes due to damming and sand mining, land subsidence due to groundwater extraction, and reduction of protective coastal mangroves in favor of agriculture and aquaculture. Coastal erosion is observed along many sections of the delta, with a rate of up to 50 m per year in some areas. However, the role of human activities remains difficult to assess because of its complexity. The present modeling study is designed to sort out the contribution of natural hydrodynamic redistribution of sediments from man-induced erosion. The modeling system used is based on CROCO, forced by global reanalyses at the boundaries and at the surface, including wave statistics (required by the sediment transport model). Tides and realistic river forcing are also included. Calibration and validation relies on a combination of in situ and remotely-sensed observations, and laboratory experiments. Once validated, coastal dynamics are investigated by performing sensitivity experiments for both the hydro- and sediment dynamics. The results suggest that while wind is the main factor driving the coastal currents, the sediment dynamics is essentially the result of re-suspension due to wave-induced bed shear stress. The suspended sediments are then redistributed by coastal currents that are not limited to the nearshore zone. Strong seasonality of the process is observed with the northeast winter monsoon being the season of strongest re-suspension and sediment redistribution. The annual sediment budget is characterized by important local disequilibrium, with alongshore patterns that are in agreement with the observed shoreline evolution. The effect of a decrease in river sediment supply is difficult to evaluate because the estuarine zone is still in accretion, apart from the particular case of Go Cong shores. Far from the estuarine zone, subsidence is an additional strong candidate to explain erosion in areas that should naturally be accreting. Synthesizing these results, the study proposes a first attempt at a “taxonomy and geography” of processes along the coastal Mekong delta that can explain the recent observations of shoreline changes and help design protection measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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The aim of this study was the development of nanostructured lipid carriers (NLCs) decorated with a polycationic cell-penetrating peptide (CPP). A coating with polyphosphates (PP) ...enables charge conversion at target cells being triggered by the membrane bound enzyme intestinal alkaline phosphatase (IAP).
The CPP, stearyl-nona-L-arginine (R9SA) was obtained by solid phase synthesis. Formed nanocarriers were characterized regarding size, polydispersity index, zeta potential and charge conversion in the presence of IAP and on Caco-2 cells. The BCS class IV drug saquinavir (SQV) was loaded into NLCs in different concentrations. Mucus diffusion ability of the NLCs was evaluated by the rotating tube method. Furthermore, cellular uptake was evaluated on Caco-2 cells and endosomal escape properties were investigated using erythrocytes.
All NLCs were obtained in a size range between 146 nm and 152 nm and a polydispersity index of 0.2. Incubation of PP coated PP-R9SA-NLCs with IAP led to a charge conversion from −41.8 mV to 6.4 mV (Δ48.2 mV). After four hours of incubation with IAP, phosphate release reached a plateau, indicating a faster polyphosphate cleavage than on Caco-2. Drug load and encapsulation efficiency of SQV was obtained up to 80.6% and 46.5 µg/mg. Mucus diffusion was increasing in the following rank order: R9SA-NLCs < blank NLCs < PP-R9SA-NLCs. R9SA-NLCs and PP-R9SA-NLCs increased the cellular uptake 15.6- and 13.2-fold, respectively, compared to the control NLCs. Erythrocytes interaction study revealed enhanced endosomal escape properties for R9SA-NLCs and PP-R9SA-NLCs when incubated with IAP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mucus permeation, mucoadhesion and cell membrane interaction are properties that a drug carrier needs to deliver macromolecule compounds through the mucus barrier and inside epithelial cells ...effectively. Herein, we prepared micelles from phosphorylated chitosan-stearic acid conjugates (CSSAP) possessing those properties. Their zeta potential can be shifted from negative to neutral once contacting with alkaline phosphatase (ALP). CSSAP micelles showed effective mucus permeation and cell association, thus could be used as a promising platform for mucosal drug delivery. CSSAP was obtained via two modifications: alkylation of CS with stearic acid (termed CSSA) followed by phosphorylation utilizing phosphorus pentoxide. CSSAP had critical micelle concentration value of 76 μg/mL and phosphate content of 1066 μmol/g polymer. Micelle hydrodynamic size was 50–60 nm. Upon contacting with ALP, the polymeric micelles showed a phosphate release of 626 μmol/g polymer (~60%) and a zeta potential shift from −20 to −9 mV within 30 min. They exhibited 6-times higher mucus permeation capacity than positively charged CSSA micelles. CSSAP micelles association to Caco-2 and HEK 293 cells depended on the ALP activity. On Caco-2 cells, cell association rate after 3 h was 2-times higher compared to association rate in the presence of 0.5% phosphatase inhibitors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, ...however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE. 3-((2-Acetamido-3-methoxy-3-oxopropyl)dithio) propanoic acid was covalently attached to Ch via a carbodiimide-mediated reaction. Low-, medium-, and high-modified Chs (Ch-SS-1, Ch-SS-2, and Ch-SS-3) with 54, 107 and 140 μmol of ligand per gram of polymer, respectively, were tested. In parallel, three thiolated Chs, namely Ch-SH-1, Ch-SH-2, and Ch-SH-3, were prepared by conjugating N-acetyl cysteine to Ch at the same degree of modification to compare the effectiveness of disulfide versus thiol modification on cell adhesion. Ch-SS-1 showed better cell adhesion capability than Ch-SS-2 and Ch-SS-3. This can be explained by the more lipophilic surfaces of Ch-SS as a higher modification was made. Although Ch-SH-1, Ch-SH-2, and Ch-SH-3 were shown to be good substrates for cell adhesion, growth, and proliferation, Ch-SS polymers were superior to Ch-SH polymers in the formation of 3D cell cultures. Cryogels structured by Ch-SS-1 (SSg) resulted in homogeneous scaffolds with tunable pore size and mechanical properties by changing the mass ratio between Ch-SS-1 and heparin used as a cross-linker. SSg scaffolds possessing interconnected microporous structures showed good cell migration, adhesion, and proliferation. Therefore, Ch-SS can be used to construct tunable cryogel scaffolds that are suitable for 3D cell culture and TE.
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IJS, KILJ, NUK, PNG, UL, UM
Dengue is the most prevalent arboviral disease of humans. The host and virus variables associated with dengue virus (DENV) transmission from symptomatic dengue cases (n = 208) to Aedes aegypti ...mosquitoes during 407 independent exposure events was defined. The 50% mosquito infectious dose for each of DENV-1-4 ranged from 6.29 to 7.52 log10 RNA copies/mL of plasma. Increasing day of illness, declining viremia, and rising antibody titers were independently associated with reduced risk of DENV transmission. High early DENV plasma viremia levels in patients were a marker of the duration of human infectiousness, and blood meals containing high concentrations of DENV were positively associated with the prevalence of infectious mosquitoes 14 d after blood feeding. Ambulatory dengue cases had lower viremia levels compared with hospitalized dengue cases but nonetheless at levels predicted to be infectious to mosquitoes. These data define serotype-specific viremia levels that vaccines or drugs must inhibit to prevent DENV transmission.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Since the 1960s the membrane‐bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even from the surface ...of nanocarriers, this enzyme enables the design of drug delivery systems that can alter their properties in the body on demand. Anionic nanocarriers exhibiting bioinert properties can alter their surface to interactive once having reached the target site as due to an ALP‐triggered cleavage of anionic phosphate groups from their surface charge converts to cationic improving for instance cellular uptake. Moreover, features such as the accumulation of nanocarriers at the target site or a targeted drug release triggered by ALP can be introduced. In addition, ALP is utilized to improve the potential of numerous diagnostic systems. Within this review, one provides an overview about the activity, selectivity, and distribution of this enzyme, as well as the great variety of applications in drug delivery and diagnostics making use of it.
Alkaline phosphatase has been an endogenous partner for phosphate prodrugs for decades. More recently, it has been utilized as a reliable partner for enzyme‐responsive drug nanocarriers and diagnostic systems constructed from novel phosphate‐functionalized biomaterials.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Ag/GO was successfully synthesized by co-precipitation.•LAA was used as a reducing agent, which is easy to find, and eco-friendly.•AgNPs with size 17.65 ± 4.76 nm were decorated on GO.•Concentration ...and contact time significantly affect the antibacterial activity.•The antibacterial activity of Ag/GO increased when pH value was decreased.
Herein, silver/graphene oxide (Ag/GO) nanocomposite was fabricated by co-precipitation with green reducing agent and then was characterized with modern analytical techniques. The antibacterial activities were conducted via the effects of Ag/GO concentration, time, and pH. Results show that silver nanoparticles were uniformly distributed on the GO sheets nanosized of 17.65 ± 4.76 nm. The antibacterial performance was optimized at pH 5.6, eradicating P. aeruginosa in 180 min at 50 µg/mL Ag/GO concentration and S. aureus in 480 min at 300 µg/mL Ag/GO. This demonstrates the potential of Ag/GO as an antibacterial nanocomposite material.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To prepare new polycationic pullulan derivatives exhibiting highly mucoadhesive and sustained drug release properties.
Hydroxy groups of pullulan were activated with mesyl chloride followed by ...conjugation with low-molecular weight polyamines. Pullulan-tris(2-aminoethyl)amine (Pul-TAEA) and pullulan-polyethyleneimine (Pul-PEI) were evaluated regarding swelling behaviour, mucoadhesive properties and potential to control drug release.
Pul-TAEA and Pul-PEI exhibited excellent swelling properties at pH 6.8 showing 240- and 370-fold increase in weight. Compared to unmodified pullulan, Pul-TAEA and Pul-PEI displayed 5- and 13.3-fold increased dynamic viscosity in mucus. Mucoadhesion studies of Pul-TAEA and Pul-PEI on intestinal mucosa showed a 6- and 37.8-fold increase in tensile strength, and a 72- and 120-fold increase in mucoadhesion time compared to unmodified pullulan, respectively. Due to additional ionic interactions between cationic groups on polyaminated pullulans and an anionic model drug, a sustained drug release was achieved.
Polyaminated pullulans are promising novel mucoadhesive excipients for mucosal drug delivery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to synthesize novel polymeric excipients forming mucoadhesive films for treatment of vaginal microbial infections. 2-(2-Amino ethyldisulfanyl) nicotinic acid was conjugated ...with gellan gum via amide bond formation. The structure of the resulting S-protected gellan gum was confirmed by 1H NMR. S-protected gellan gum variants were characterized for thiol content, cytotoxicity, rheological behaviour and film forming capability. Depending on the added amount of AMENA degree of thiolation was 81 ± 13 (S-GG 81) and 174 ± 16 (S-GG 174) μmol/g, respectively. Vaginal films were casted from S-protected gellan gum variants and studied for adherence to vaginal mucosa, drug release and antimicrobial activity. S-protected gellan gum remained biocompatible showing >87% cell viability. S-GG 81 and S-GG 174 exhibited 1.84- and 4.3-fold increased dynamic viscosity in porcine mucus in comparison to unmodified gellan gum, respectively. Compared to gellan gum films, thiol functionalized gellan gum films showed 3-fold improved adhesion on mucosal surface over a period of 3 h along with significant antimicrobial activity. Moreover, S-protected gellan gum provided a sustained release of metronidazole. According to these results, S-protected gellan gum proved to be a promising novel excipient for casting vaginal films, exhibiting strongly improved mucoadhesive and antimicrobial properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP