Orally deliverable strategy based on microalgal biomass for intestinal disease treatment.
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ABSTRACT:
SUBMITTER: Zhong D
PROVIDER: S-EPMC8612690 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose: Colitis-associated colorectal cancer (CAC) poses substantial challenges for effective treatment. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the safe and effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract. Experimental Design: In this study, we developed orally deliverable nanotherapeutics for the synergistic treatment of inflammatory bowel diseases (IBDs) and CAC. Water-insoluble curcumin (CUR) and 7-ethyl-10-hydroxycamptothecin (SN38), which served as anti-inflammatory and cytotoxic agents, respectively, were chemically engineered into hydrophilic mucoadhesive chitosan for the generation of chitosan-drug amphiphiles. Results: The resulting amphiphilic constructs formed core-shell nanostructures in aqueous solutions and were orally administered for in vivo therapeutic studies. Using a preclinical CAC mouse model, we showed that the orally delivered nanotherapeutics locally accumulated in inflamed intestinal regions and tumor tissues. Furthermore, the therapeutic synergy of the combined nanotherapeutics in CAC mice was evaluated. Compared with their individual drug forms, combined CUR and SN38 nanoparticles yielded synergistic effects to alleviate intestinal inflammation and protect mice from ulcerative colitis. Notably, the combinatorial therapy demonstrated a remarkable tumor shrinkage with only ~6% of the total tumors exceeding 4 mm in diameter, whereas ~35% of tumors were observed to exceed a diameter of 4 mm in the saline-treated CAC mice. These data suggest a new and reliable approach for improving the treatment of IBD and CAC. Conclusions: Our results showed that bioadhesive chitosan materials can be used to produce colloidal-stable nanotherapeutics that are suitable for oral delivery. Both nanotherapeutics exhibited substantial accumulation in inflamed intestinal regions and tumor tissues and showed good synergy for treating CAC, warranting further clinical translation.
| S-EPMC6831307 | biostudies-literature
Project description:Spinal muscular atrophy (SMA) is 1 of the leading causes of infant mortality. SMA is mostly caused by low levels of Survival Motor Neuron (SMN) protein due to deletion of or mutation in the SMN1 gene. Its nearly identical copy, SMN2, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Correction of SMN2 exon 7 splicing by an antisense oligonucleotide (ASO), nusinersen (Spinraza™), that targets the intronic splicing silencer N1 (ISS-N1) became the first approved therapy for SMA. Restoration of SMN levels using gene therapy was the next. Very recently, an orally deliverable small molecule, risdiplam (Evrysdi™), became the third approved therapy for SMA. Here we discuss how these therapies are positioned to meet the needs of the broad phenotypic spectrum of SMA patients.
| S-EPMC7691903 | biostudies-literature
Project description:BackgroundMicroalgae are well-established feedstocks for applications ranging from biofuels to valuable pigments and therapeutic proteins. However, the low biomass productivity using commercially available growth mediums is a roadblock for its mass production. This work describes a strategy to boost algal biomass productivity by using an effective CO2 supplement.ResultsIn the present study, a novel nanoemulsion-based media has been tested for the growth of freshwater microalgae strain Chlorella pyrenoidosa. Two different nanoemulsion-based media were developed using 1% silicone oil nanoemulsion (1% SE) and 1% paraffin oil nanoemulsion (1% PE) supplemented in Blue-green 11 media (BG11). After 12 days of cultivation, biomass yield was found highest in 1% PE followed by 1% SE and control, i.e., 3.20, 2.75, and 1.03 g L-1, respectively. The chlorophyll-a synthesis was improved by 76% in 1% SE and 53% in 1% PE compared with control. The respective microalgal cell numbers for 1% PE, 1% SE and control measured using the cell counter were 3.00 × 106, 2.40 × 106, and 1.34 × 106 cells mL-1. The effective CO2 absorption tendency of the emulsion was highlighted as the key mechanism for enhanced algal growth and biomass production. On the biochemical characterization of the produced biomass, it was found that the nanoemulsion-cultivated C. pyrenoidosa had increased lipid (1% PE = 26.80%, 1% SE = 23.60%) and carbohydrates (1% PE = 17.20%, 1% SE = 18.90%) content compared to the control (lipid = 18.05%, carbohydrates = 13.60%).ConclusionsThis study describes a novel nanoemulsion which potentially acts as an effective CO2 supplement for microalgal growth media thereby increasing the growth of microalgal cells. Further, nanoemulsion-cultivated microalgal biomass depicts an increase in lipid and carbohydrate content. The approach provides high microalgal biomass productivity without altering morphological characteristics like cell shape and size as revealed by field emission scanning electron microscope (FESEM) images.
| S-EPMC8091788 | biostudies-literature
Project description:This paper deals with the additive manufacturing of metakaolin-based geopolymers and with the use of microalgal biomass from wastewater treatment plants as biofiller in this kind of cementitious material. The study was developed following the evolution stages of the material, which was prepared and printed as a soft paste and then hardened thanks to an inorganic polymerization reaction (geopolymerization). Thus, the characterization techniques adopted encompassed rheometry, mechanical tests performed on the hardened material, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and mercury intrusion porosimetry (MIP). Microalgal biomass addition, evaluated in this study at 1, 3 and 5 php with respect to the powder weight, affected both the properties of the fresh and of the hardened material. Regarding the former aspect, biomass reduced the yield stress of the pastes, improving the ease of the extrusion process, but potentially worsening the ability to build structures in height. When hardened, geopolymers containing microalgae showed mechanical properties comparable to the unfilled material and a microstructure characterized by smaller pores. Finally, a printing test was successfully performed with a larger printer to assess the feasibility of producing large-scale structures. Taking into account these results, this study demonstrates the possibility of using microalgal biomass as biofiller in geopolymers for additive manufacturing.
| S-EPMC6479326 | biostudies-literature
Project description:Microalgal biomass is a promising feedstock for biofuels, feed/food and biomaterials. However, while production and commercialization of single-product commodities is still not economically viable, obtaining multiple products in a biomass biorefinery faces several techno- economic challenges. The aim of this study was to identify a suitable source of hydrolytic enzymes for algal biomass saccharification. Screening of twenty-six fungal isolates for secreted enzymes activity on Chlamydomonas reinhardtii biomass resulted in the identification of Aspergillus niger IB-34 as a candidate strain. Solid state fermentation on wheat bran produced the most active enzyme preparations. From sixty-five proteins identified by LC-MS, the majority corresponded to predicted secreted proteins belonging to the Gene Ontology categories of catalytic activity/hydrolase activity on glycosyl and O-glycosyl compounds. Defatted biomass of the more biotechnologically relevant strains towards the production of commodities, Chlorella sorokiniana and Scenedesmus obliquus, was fully saccharified after a mild pretreatment at 80 °C for 10 min, at a high biomass load of 10 % (w/v). Deffated and 2 saccharified biomass of both strains was further converted into ethanol by fermentation with Saccharomyces cerevisiae at a theoretical maximum efficiency, either by separated or simultaneous sccharification and fermentation. The resulting insoluble protein after biomass defatting with an organic solvent and enzymatic saccharification resulted in a high digestibility in an in vitro digestion assay. Proof-of-concept is presented for an enzyme-assisted biomass biorefinery which recovered 81% of the main biomass fractions in a likely active form for the conversion of lipids and carbohydrates into biofuels and proteins into feed/food.
2023-03-10 | PXD034998 | Pride
Project description:A dynamic coarse-grained model of microalgal growth considering light availability and temperature under discontinuous bioprocess operation was parameterized using experimental data from 15 batch cultivations of Nannochloropsis granulata in a pilot-scale tubular photobioreactor. The methodology applied consists of a consecutive two-step model parameter estimation using pooled, clustered and reorganized data to obtain initial estimates and multi-experiment fitting to obtain the final estimates, which are: maximum specific growth rate μmax = 1.56 d-1, specific photon half-saturation constant K S,ph = 1.89 mol ph g X - 1 d - 1 , specific photon maintenance coefficient m ph = 0.346 mol ph g X - 1 d - 1 and the cardinal temperatures T min = 2.3°C, T opt = 27.93°C and T max = 32.59°C. Biomass productivity prediction proved highly accurate, expressed by the mean absolute percent error MAPE = 7.2%. Model-based numerical optimization of biomass productivity for repeated discontinuous operation with respect to the process parameters cultivation cycle time, inoculation biomass concentration and temperature yielded productivity gains of up to 35%. This optimization points to best performance under continuous operation. The approach successfully applied here to small pilot-scale confirms an earlier one to lab-scale, indicating its transferability to larger scale tubular photobioreactors.
| S-EPMC7247861 | biostudies-literature
Project description:The processing volume of bioengineering operations requires flow properties of algal mass for effective processing techniques. Chlorella Vulgaris microalgae cultured at 25 °C in Tap media under continuous illumination was considered. It showed an exponential phase of growth up to 8 days and then a stationary phase of growth from 8 days to 15 days. The rheological properties of microalgae biomass during the growth represented power law model. Microscopic analysis showed the influence of shearing on variation of algal structure from clusters to complete cell separation. The flow properties supported the microscopy analysis showing the shear thickening property at high shear rates and shear thinning nature at low shear regime. Optimal power required for the agitation of biomass based on the variations of non-Newtonian viscosity were predicted by considering the vessel geometry.
| S-EPMC6562143 | biostudies-literature
Project description:BackgroundMicroalgae are touted as an attractive alternative to traditional forms of biomass for biofuel production, due to high productivity, ability to be cultivated on marginal lands, and potential to utilize carbon dioxide (CO2) from industrial flue gas. This work examines the fossil energy return on investment (EROIfossil), greenhouse gas (GHG) emissions, and direct Water Demands (WD) of producing dried algal biomass through the cultivation of microalgae in Open Raceway Ponds (ORP) for 21 geographic locations in the contiguous United States (U.S.). For each location, comprehensive life cycle assessment (LCA) is performed for multiple microalgal biomass production pathways, consisting of a combination of cultivation and harvesting options.ResultsResults indicate that the EROIfossil for microalgae biomass vary from 0.38 to 1.08 with life cycle GHG emissions of -46.2 to 48.9 (g CO2 eq/MJ-biomass) and direct WDs of 20.8 to 38.8 (Liters/MJ-biomass) over the range of scenarios analyzed. Further anaylsis reveals that the EROIfossil for production pathways is relatively location invariant, and that algae's life cycle energy balance and GHG impacts are highly dependent on cultivation and harvesting parameters. Contrarily, algae's direct water demands were found to be highly sensitive to geographic location, and thus may be a constraining factor in sustainable algal-derived biofuel production. Additionally, scenarios with promising EROIfossil and GHG emissions profiles are plagued with high technological uncertainty.ConclusionsGiven the high variability in microalgae's energy and environmental performance, careful evaluation of the algae-to-fuel supply chain is necessary to ensure the long-term sustainability of emerging algal biofuel systems. Alternative production scenarios and technologies may have the potential to reduce the critical demands of biomass production, and should be considered to make algae a viable and more efficient biofuel alternative.
| S-EPMC3693881 | biostudies-literature
Project description:It is established that biodiversity determines productivity of natural ecosystems globally. We have proved that abiotic factors influenced biomass productivity in engineered ecosystems i.e. high rate algal ponds (HRAPs), previously. This study demonstrates that biotic factors, particularly microalgal diversity, play an essential role in maintaining stable biomass productivity in HRAP treating municipal wastewater by mutualistic adaptation to environmental factors. The current study examined data from the second year of a two-year study on HRAP treating municipal wastewater. Microalgal diversity, wastewater characteristics, treatment efficiency and several environmental and meteorological factors were documented. Multivariate statistical analyses reveal that microalgae in uncontrolled HRAPs adapt to adverse environmental conditions by fostering diversity. Subsequently, five dominant microalgal strains by biovolume were isolated, enriched, and optimum conditions for high biomass productivity were ascertained. These laboratory experiments revealed that different microalgal strains dominate in different conditions and a consortium of these diverse taxa help in sustaining the algae community from environmental and predatory pressures. Diversity, niche or seasonal partitioning and mutualistic growth are pertinent in microalgal cultivation or wastewater treatment. Therefore, enrichment of selective species would deprive the collective adaptive ability of the consortium and encourage system vulnerability especially in wastewater treatment.
| S-EPMC5434013 | biostudies-literature
Project description:Microalga is a promising biomass feedstock to restore the global carbon balance and produce sustainable bioenergy. However, the present biomass productivity of microalgae is not high enough to be marketable mainly because of the inefficient utilization of solar energy. Here, we study optical engineering strategies to lead to a breakthrough in the biomass productivity and photosynthesis efficiency of a microalgae cultivation system. Our innovative optical system modelling reveals the theoretical potential (>100 g m-2 day-1) of the biomass productivity and it is used to compare the optical aspects of various photobioreactor designs previously proposed. Based on the optical analysis, the optimized V-shaped configuration experimentally demonstrates an enhancement of biomass productivity from 20.7 m-2 day-1 to 52.0 g m-2 day-1, under the solar-simulating illumination of 7.2 kWh m-2 day-1, through the dilution and trapping of incident energy. The importance of quantitative optical study for microalgal photosynthesis is clearly exhibited with practical demonstration of the doubled light utilization efficiencies.
| S-EPMC6370833 | biostudies-literature