Design of Collagen and Gelatin-based Electrospun Fibers for Biomedical Purposes: An Overview.

Collagen and gelatin are essential natural biopolymers commonly utilized in biomaterials and tissue engineering because of their excellent physicochemical and biocompatibility properties. They can be used either in combination with other biomacromolecules or particles or even exclusively for the enhancement of bone regeneration or for the development of biomimetic scaffolds. Collagen or gelatin derivatives can be transformed into nanofibrous materials with porous micro- or nanostructures and superior mechanical properties and biocompatibility using electrospinning technology. Specific attention was recently paid to electrospun mats of such biopolymers, due to their high ratio of surface area to volume, as well as their biocompatibility, biodegradability, and low immunogenicity. The fiber mats with submicro- and nanometer scale can replicate the extracellular matrix structure of human tissues and organs, making them highly suitable for use in tissue engineering due to their exceptional bioaffinity. The drawbacks may include rapid degradation and complete dissolution in aqueous media. The use of gelatin/collagen electrospun nanofibers in this form is thus greatly restricted for biomedicine. Therefore, the cross-linking of these fibers is necessary for controlling their aqueous solubility. This led to enhanced biological characteristics of the fibers, rendering them excellent options for various biomedical uses. The objective of this review is to highlight the key research related to the electrospinning of collagen and gelatin, as well as their applications in the biomedical field. The review features a detailed examination of the electrospinning fiber mats, showcasing their varying structures and performances resulting from diverse solvents, electrospinning processes, and cross-linking methods. Judiciously selected examples from literature will be presented to demonstrate major advantages of such biofibers. The current developments and difficulties in this area of research are also being addressed.

Tuning the water intrinsic permeability of PEGDA hydrogel membranes by adding free PEG chains of varying molar masses.

We explore the effect of poly(ethylene glycol) (PEG) molar mass on the intrinsic permeability and structural characteristics of poly(ethylene glycol) diacrylate PEGDA/PEG composite hydrogel membranes. We observe that by varying the PEG content and molar mass, we can finely adjust the water intrinsic permeability by several orders of magnitude. Notably, we show the existence of maximum water intrinsic permeability, already identified in a previous study to be located at the critical overlap concentration C* of PEG chains, for the highest PEG molar mass studied. Furthermore, we note that the maximum intrinsic permeability follows a non-monotonic evolution with respect to the PEG molar mass and reaches its peak at 35 000 g mol-1. Besides, our results show that a significant fraction of PEG chains is irreversibly trapped within the PEGDA matrix even for the lowest molar masses down to 600 g mol-1. This observation suggests the possibility of covalent grafting of the PEG chains onto the PEGDA matrix. CryoSEM and AFM measurements demonstrate the presence of large micron-sized cavities separated by PEGDA-rich walls whose nanometric structures strongly depend on the PEG content. By combining our permeability and structural measurements, we suggest that the PEG chains trapped inside the PEGDA-rich walls induce nanoscale defects in the crosslinking density, resulting in increased permeability below C*. Conversely, above C*, we speculate that partially trapped PEG chains may form a brush-like arrangement on the surface of the PEGDA-rich walls, leading to a reduction in permeability. These two opposing effects are anticipated to exhibit molar-mass-dependent trends, contributing to the non-monotonic variation of the maximum intrinsic permeability at C*. Overall, our results demonstrate the potential to fine-tune the properties of hydrogel membranes, offering new opportunities for separation applications.

Green Synthesis of Zein-Based Nanoparticles Encapsulating Lupulone: Antibacterial and Antiphotoaging Agents.

Prolonged skin exposure to UV radiation may result in sunburn, with possible inflammatory and oxidative stress to the skin, skin photoaging, photocarcinogenesis, even DNA damage, and apoptosis if sunscreen protection is not used. Due to the advantages that they offer, high encapsulation capability, increased stability of encapsulated bioactive agents, and release control, nanoparticulate materials have been used in sunscreens despite the hazard that they present: their capacity to penetrate the skin causing toxic side effects (especially the chemical sunscreens). The present study reports the preparation of nanoparticulate composites containing only GRAS substances and using an eco-friendly, inexpensive procedure. The ingredients used have properties that are beneficial to the skin. Zein (Z), a prolamin-rich protein from corn, is biodegradable and biocompatible, is a moisture attractor, and shows effective absorption by cells. Lupulone (L), extracted from hops, is an antibacterial and antioxidant agent that has a stimulating effect on the collagen production in the body due to its content of phytohormones. Gum arabic (GA) is a natural glycoprotein used in beverages and cosmetics as an emulsifier/stabilizer. Composite matrices containing Z/GA/L were prepared using a simple method (antisolvent), which replaces the flammable solvent ethanol with aqueous propylene glycol. The nanocomposites were characterized by FTIR, composition, encapsulation efficiency, and loading capacity for L, size, zeta potential, and morphology (SEM). Their biological activity was investigated as well. The zein-based nanoparticles showed antioxidant and antimicrobial effects (even some synergistic, unexpected behavior) and modulatory activity on the matrix metalloproteinase MMP-1. Due to their properties, the nanoparticles discussed herein show potential for use in formulations for the skin, especially for mature skin, replacing chemical substances with potential side effects used typically in topical delivery systems.

Sieving and Clogging in PEG-PEGDA Hydrogel Membranes.

Hydrogels are promising systems for separation applications due to their structural characteristics (i.e., hydrophilicity and porosity). In our study, we investigate the permeation of suspensions of rigid latex particles of different sizes through free-standing hydrogel membranes prepared by photopolymerization of a mixture of poly(ethylene glycol) diacrylate (PEGDA) and large poly(ethylene glycol) (PEG) chains of 300,000 g·mol-1 in the presence of a photoinitiator. Atomic force microscopy and cryoscanning electron microscopy (cryoSEM) were employed to characterize the structures of the hydrogel membranes. We find that the 20 nm particle permeation depends on both the PEGDA/PEG composition and the pressure applied during filtration. In contrast, we do not measure a significant permeation of the 100 nm and 1 µm particles, despite the presence of large cavities of 1 µm evidenced by the cryoSEM images. We suggest that the PEG chains induce local nanoscale defects in the cross-linking of PEGDA-rich walls separating the micrometer-sized cavities, which control the permeation of particles and water. Moreover, we discuss the decline of the permeation flux observed in the presence of latex particles compared to that of pure water. We suggest that a thin layer of particles forms on the surface of the hydrogels.

Design of Tailor-Made Biopolymer-Based Capsules for Biological Application by Combining Porous Particles and Polysaccharide Assembly.

Various approaches have been described in the literature to demonstrate the possibility of designing biopolymer particles with well-defined characteristics, such as size, chemical composition or mechanical properties. From a biological point of view, the properties of particle have been related to their biodistribution and bioavailability. Among the reported core-shell nanoparticles, biopolymer-based capsules can be used as a versatile platform for drug delivery purposes. Among the known biopolymers, the present review focuses on polysaccharide-based capsules. We only report on biopolyelectrolyte capsules fabricated by combining porous particles as a template and using the layer-by-layer technique. The review focuses on the major steps of the capsule design, i.e., the fabrication and subsequent use of the sacrificial porous template, multilayer coating with polysaccharides, the removal of the porous template to obtain the capsules, capsule characterisation and the application of capsules in the biomedical field. In the last part, selected examples are presented to evidence the major benefits of using polysaccharide-based capsules for biological purposes.

Cyclodextrin-Calcium Carbonate Micro- to Nano-Particles: Targeting Vaterite Form and Hydrophobic Drug Loading/Release.

Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient's recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO3) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO3 micro- to nano-particles have been fabricated by combining Na2CO3 solution and CaCl2 solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the Na2CO3 and CaCl2 concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO3 particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca2+. The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).

Impact of tannic acid on nisin encapsulation in chitosan particles.

This study investigates the effect of addition of tannic acid on nisin encapsulated in chitosan matrices. Composite materials were prepared using a mild, environmentally friendly procedure, ionotropic gelation of chitosan by sodium tripolyphosphate in the presence of nisin (N) at different concentrations. In two parallel sets of preparations, tannic acid (TA) was added at 10:1 and 5:1 N:TA, respectively. The obtained particles were characterized by FTIR, SEM, size, zeta potential, encapsulation efficiency, loading capacity, and ratio of residual free amino groups. The kinetics of nisin release from the particles was studied to assess the role of TA as a potential modulator thereof. Its addition resulted in enhanced release, higher at lower N:TA ratio. An additional benefit was that TA, a strong antioxidant, imparted antioxidant activity to the composites. Antimicrobial turbidimetric tests were performed against one gram-positive bacterium (Staphylococcus aureus) and two gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), all relevant for the food, pharmaceutical, and cosmetic industries. All the composites showed synergistic effects against all the bacteria tested. The positive coaction was stronger against the gram-negative species. This is remarkable since nisin by itself has not known activity against them.

Metabolomic disorders unveil hepatotoxicity of environmental microplastics in wild fish Serranus scriba (Linnaeus 1758).

Coastal areas are worldwide subject to large inputs of anthropogenic wastes that are discharged directly into inshore waters, where they will be weathered into small microplastics (MPs) of up to a size <20 µm. This study provides information about the presence of small environmental MPs (≤3 µm) in the liver of adult benthopelagic fish Serranus scriba (Linnaeus 1758), caught from three coastal regions in Tunisia distinguished by different patterns of human activity. Polymer composition in fish liver was identified using Raman microspectroscopy. Results revealed differences in the abundance, size distribution and presence of plastic additives over the investigated sites. Polyethylene-vinyl acetate (PEVA: 34% particles/g of tissue), high density polyethylene (HDPE: 24.4%) and the two smaller size classes, i.e. 3-1.2 µm and 1.2-0.45 µm, were the most abundant MPs types and size distribution found, respectively, in Bizerte channel (BC) site (Bizerte city, Tunisia). Moreover, at hepatic level data showed a significant site-dependent cytotoxicity expressed by changes in malondialdehyde (MDA) content, presence of reactive oxygen species (ROS) expressed by altered level of catalase (CAT) and glutathione-S-transferase (GST) activities and in the content of metallothioneins (MTs), as well as genotoxicity by changes in the amount of micronucleus (MN), and neurotoxicity by altered activity of acetylcholinesterase (AChE). A innovative metabolomics analysis was also performed to further investigate the distinct patterns of key metabolite changes in the liver of Serranus scriba. A total of 36 metabolites were significantly affected, mainly involved in energy, amino acid and osmolyte metabolism. These findings emphasised for the first time a close relationship between the source, abundance and size ranges of environmental MPs ≤ 3 µm and their hepatotoxicity in wild organisms.

Autophagic event and metabolomic disorders unveil cellular toxicity of environmental microplastics on marine polychaete Hediste diversicolor.

Although the hazards of microplastics (MPs) have been quite well explored, the aberrant metabolism and the involvement of the autophagy pathway as an adverse response to environmental MPs in benthic organisms are still unclear. The present work aims to assess the impact of different environmental MPs collected from the south coast of the Mediterranean Sea, composed by polyethylene (PE), polyethylene vinyl acetate (PEVA), low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP) and polyamide (PA) on the metabolome and proteome of the marine polychaete Hediste diversicolor. As a result, all the microplastic types were detected with Raman microspectroscopy in polychaetes tissues, causing cytoskeleton damage and induced autophagy pathway manifested by immunohistochemical labeling of specific targeted proteins, through Tubulin (Tub), Microtubule-associated protein light chain 3 (LC3), and p62 (also named Sequestosome 1). Metabolomics was conducted to further investigate the metabolic alterations induced by the environmental MPs-mixture in polychaetes. A total of 28 metabolites were differentially expressed between control and MPs-treated polychaetes, which showed elevated levels of amino acids, glucose, ATP/ADP, osmolytes, glutathione, choline and phosphocholine, and reduced concentration of aspartate. These novel findings extend our understanding given the toxicity of environmental microplastics and unravel their underlying mechanisms.

Multilayer dextran derivative based capsules fighting bacteria resistant to Antibiotic: Case of Kanamycin-Resistant Escherichia coli.

Bacteria resistance to antibiotics has emerged as a major health problem. Developing new antibacterial systems is then of major interest. In this sense, we present biocapsules presenting inherent antibacterial capacity. The self-assembly of charged biopolymer, namely diethylaminoethyl-dextran hydrochloride (dex+) and dextran sulfate (dex-), were done on calcium carbonate microparticles, used as a template. Zeta potential measurements have shown the successful alternate adsorption of these biopolymers and related charge reversal upon the multilayer film construction onto the particles surface. The shape of the capsules was characterized by scanning electron microscopy (SEM). These particles were tested against bacteria resistant to antibiotics, namely kanamycin-resistant Escherichia coli. An inhibitory effect of the particles was observed during bacterial growth in liquid medium, i.e. in the range of 10 % for (dex+/dex-)n coated CaCO3 materials and of 50% for (dex+/dex-)n capsules. These findings evidence the high potential of capsules to act as antimicrobial agents in future and in treatments against infections.

Controlling the growth of Escherichia coli by layer-by-layer encapsulation.

Escherichia coli is one of the most common commensal aerobic bacteria in the gut microbiota of humans (and other mammals). Nevertheless, if left free to proliferate, it can induce a large range of diseases from diarrhoea to extra-intestinal diseases. In recent years, this bacterium had become increasingly resistant to antibiotics. It is therefore essential to implement new approaches able to maintain both bacterial viability and to control their proliferation. In this context, we developed a process to encapsulate Escherichia coli in polymer shells. We took advantage of the fact that this bacterium has a negatively charged surface and modified it via a layer-by-layer process, i.e. with oppositely charged polyelectrolyte pairs (namely chitosan as the polycation and alginate or dextran sulfate as polyanion). We successfully demonstrate the controlled coating of the bacterial surface via zeta potential measurement, the viability of the encapsulated bacteria and a delay in growth due to the multilayer coating. This delay was dependent on the number of polyelectrolyte layers.

Cell surface nucleolin as active bait for nanomedicine in cancer therapy: a promising option.

Conventional chemotherapy used against cancer is mostly limited due to their non-targeted nature, affecting normal tissue and causing undesirable toxic effects to the affected tissue. With the aim of improving these treatments both therapeutically and in terms of their safety, numerous studies are currently being carried out using nanoparticles (NPs) as a vector combining tumor targeting and carrying therapeutic tools. In this context, it appears that nucleolin, a molecule over-expressed on the surface of tumor cells, is an interesting therapeutic target. Several ligands, antagonists of nucleolin of various origins, such as AS1411, the F3 peptide and the multivalent pseudopeptide N6L have been developed and studied as therapeutic tools against cancer. Over the last ten years or so, numerous studies have been published demonstrating that these antagonists can be used as tumor targeting agents with NPs from various origins. Focusing on nucleolin ligands, the aim of this article is to review the literature recently published or under experimentation in our research team to evaluate the efficacy and future development of these tools as anti-tumor agents.

Uptake, tissue distribution and toxicological effects of environmental microplastics in early juvenile fish Dicentrarchus labrax.

As the smallest environmental microplastics (EMPs), even at nanoscale, are increasingly present in the environment, their availability and physical and chemical effects on marine organisms are poorly documented. In the present study, we primarily investigated the uptake and accumulation of a mixture of environmental microplastics (EMPs) obtained during an artificial degradation process in early-juvenile sea bass (Dicentrarchus labrax). Moreover, we evaluated their hazardous effects using biochemical markers of cytotoxicity. Polymer distribution and composition in gill, gut, and liver were analyzed using polarized light microscopy (PLM) and Raman microspectroscopy (RMS). Our findings revealed the size-dependent ingestion and accumulation of smaller MPs (0.45-3 µm) in fish tissues even after a short-term exposure (3 and 5 days). In addition to MPs, our results showed the presence of plastic additives including plasticizers, flame retardants, curing agents, heat stabilizers, and fiber-reinforced plastic materials in fish tissues, which contributed mostly to the larger-sized range (≥ 1.2 µm). Our data showed that significant oxidative alterations were highly correlated with MPs size range. Our results emphasized that the toxicity of smaller EMPs (≤ 3 µm) was closely related to different factors, including the target tissue, exposure duration, size range of MPs, and their chemical properties.

Uptake, accumulation and associated cellular alterations of environmental samples of microplastics in the seaworm Hediste diversicolor.

The ubiquitous distribution of microplastics (MPs) in the marine environment raises global concern to understand their impact. Environmental MPs have been shown to exhibit different physicochemical properties during their life cycles. However, the body of knowledge regarding their accumulation and biological effects is still significantly limited compared to manufactured MPs. To evaluate the hazardous effects of a mixture of environmental MPs collected along the Tunisian beaches, their accumulation and cellular effects were investigated in Hediste diversicolor. MP sample was composed of polyethylene (PE), polyethylene vinyl acetate (PEVA), low-density polyethylene (LDPE), high-density polyethylene (HDPE), polypropylene (PP) and polyamide (PA) analyzed using Raman microspectroscopy (RM). The concentrations of MPs in seaworm tissues increased over time, following the order 1.2-0.45 µm > 3-1.2 µm > 100-3 µm. The ingestion of MPs by H. diversicolor reduced their survival and growth, affected the neuro-transmission and antioxidant pathways. Our data emphasised that the toxic effects of environmental MPs were closely related to the exposure dose and period. The results also demonstrated that the size distribution of MPs in seaworms was mainly correlated with biochemical markers. This study highlights the ecological risk in the ingestion and accumulation of environmental MPs by biota that threatens their functional parameters.

Molecular "wiring" of plasma amine oxidase: Green and enzyme friendly approaches.

The study describes two approaches to enhance oxidoreductases. Both target molecular "wiring" of enzymes using green processes. The concepts were tested on plasma amine oxidase (PAO). In the first procedure PAO was transiently exposed to an ionic liquid (IL) in the presence of redox molecules, which resulted in partial unfolding. During subsequent dialysis, the enzyme refolded entrapping redox units and affording shorter distances for electron tunneling, hence a molecular "wire" to PAO's prosthetic groups. The other procedure described herein was totally reagentless, using high hydraulic pressure (HHP) to partially denature PAO (in the presence of redox molecules) followed by dialysis and refolding. The two approaches to enzyme "wiring" are discussed comparatively from the point of view of the parameters used during the procedure, residual enzyme activity, nature of the modifier, interaction between PAO and the redox molecules, and stability over time. The most active modified PAO (PAO-ME) from each series was tested in a biosensor for amine detection, toward applications in the food industry and clinical laboratory. Our approaches used "green" reagents (IL) and were made enzyme-friendly as well by the choice of "wires".

Fabrication of large pore mesoporous silica microspheres by salt-assisted spray-drying method for enhanced antibacterial activity and pancreatic cancer treatment.

Large-pore mesoporous silica (LPMS) microspheres with tunable pore size have received intensive interest in the field of drug delivery due to their high storage capacity and fast delivery rate of drugs. In this work, a facile salt-assisted spray-drying method has been developed to fabricate LPMS microspheres using continuous spray-drying of simple inorganic salts as pore templates and colloidal SiO2 nanoparticles as building blocks, followed by washing with water to remove the templates. More importantly, the porosity of the LPMS microspheres can be finely tuned by adjusting the furnace temperature and relative concentration of the salt to SiO2, which could lead to optimal pharmaceutical outcomes. Then, the biological roles of these LPMS microspheres were evaluated in antibacterial and cancer therapy. In this regard, rhodamine b as a probe was initially loaded inside the LPMS microspheres. The obtained particles not only showed high entrapment efficiency (up to 30%) and a pH-responsive drug release but also presented pore-size-controlled drug release performance. Then, in vitro antibacterial activities of multiple antibiotics, namely nalidixic acid, chloramphenicol, and ciprofloxacin, loaded in the LPMS particles were investigated against two pathogenic bacteria, Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). The results indicated bacterial inhibition up to 70% and 20% in less than 2 h for Escherichia coli and Staphylococcus aureus, respectively. This inhibition of bacterial growth was accompanied by no bacterial regrowth within 30 h. Finally, the versatility of LPMS microspheres as drug carriers in pancreatic cancer treatment was explored. In this regard, a pro-apoptotic NCL antagonist agent (N6L) as an antitumor agent was successfully loaded onto LPMS microspheres. Interestingly, the resulting particles showed pore-size-dependent anticancer activity with inhibition of cancer cell growth up to 60%.

First report on the presence of small microplastics (≤ 3 µm) in tissue of the commercial fish Serranus scriba (Linnaeus. 1758) from Tunisian coasts and associated cellular alterations.

There is limited research on the ingestion of microplastic particles (MPs) by fish from the southern part of the Mediterranean Sea. This study provides the occurrence of small MPs (≤3 µm) in the gastrointestinal tract and muscle of adult benthopelagic fish Serranus scriba (L.1758), caught along Tunisian coasts. MPs were extracted from selected tissues using a potassium hydroxide digestion method (KOH 10%) and then quantified, and their chemical structure was characterized through Raman microspectroscopy. The results highlighted that MPs were present in all samples. The average abundance of MPs per gram of fish tissue identified through successive filters of 3 µm, 1.2 µm, and 0.45 µm differed significantly among the sites. The properties of the MPs extracted indicated that polyethylene-vinyl-acetate (PEVA: 33.45%), high density polyethylene (HD-PE: 17.33%), and fragments were the most abundant plastic types and shape found, respectively. Among those, most MPs were found at a size class of 3-1.2 µm (∼60%), especially in the muscle, suggesting a high transfer of MPs into the human diet. Our field work also aimed to explore the effects observed in the gastrointestinal tract with a battery of biomarkers assessing oxidative stress and neurotoxicity. The preliminary results of this study showed the existence of a link between small MPs, sites, and their associated urban activities and induced oxidative stress. However, more detailed studies are required to evaluate the transfer of MPs into tissues and the potential impacts of this transfer on human health.

Antibiotic loading and development of antibacterial capsules by using porous CaCO3 microparticles as starting material.

Porous calcium carbonate (CaCO3) particles have been shown to be highly advantageous for biological applications, mainly due to their large surface area and their stability in physiological media. Also, developing appropriate antibacterial materials presenting the benefits of non-formation of harmful compounds is of major interest. Two characteristics of CaCO3 particles were investigated herein: (i) antibiotic-loading capacity and (ii) the possibility of using CaCO3 particles as a template for the fabrication of biocapsules presenting inherent antibacterial capacity. The particles were tested against two representative pathogenic bacteria (Staphylococcus aureus and Escherichia coli). On one hand, a method for antibiotic (namely penicillin, ampicillin and ciprofloxacin) loading inside calcium carbonate particles was developed and antibacterial activity was investigated. Encapsulation efficiency and loading content were 95% and 5%, respectively. We showed that antibiotics prevented bacterial growth within 2 h, with no evidence of bacterial regrowth within 16 h; bactericidal effects were also observed. On the other hand, the self-assembly of charged polysaccharides, namely chitosan (chi+) and dextran sulfate (dex-), were assessed on calcium carbonate microparticles used as a sacrificial matrix. During bacterial growth in a liquid medium, an inhibitory effect of these particles was observed, i.e. Staphylococcus aureus (Gram-positive) (from 16.3% to 48.8% for (chi+/dex-)n-chi+ coated CaCO3 materials and from 41.9% to 93.0% for (chi+/dex-)n-chi+ capsules) and Escherichia coli (Gram-negative) (from 18.2% to 45.5% for (chi+/dex-)n-chi+ coated CaCO3 materials and from 40.0% to 89.1% for (chi+/dex-)n-chi+ capsules). Staining with acridine orange highlighted the bactericidal effect of the designed particles. These findings demonstrate the excellent potential of using calcium carbonate particles in antibiotic therapy as a starting point for the development of smart materials.

Aerosol-Assisted Synthesis of Tailor-Made Hollow Mesoporous Silica Microspheres for Controlled Release of Antibacterial and Anticancer Agents.

Hollow mesoporous silica microsphere (HMSM) particles are one of the most promising vehicles for efficient drug delivery owing to their large hollow interior cavity for drug loading and the permeable mesoporous shell for controlled drug release. Here, we report an easily controllable aerosol-based approach to produce HMSM particles by continuous spray-drying of colloidal silica nanoparticles and Eudragit/Triton X100 composite (EUT) nanospheres as templates, followed by template removal. Importantly, the internal structure of the hollow cavity and the external morphology and the porosity of the mesoporous shell can be tuned to a certain extent by adjusting the experimental conditions (i.e., silica to EUT mass ratio and particle size of silica nanoparticles) to optimize the drug loading capacity and the controlled-release properties. Then, the application of aerosol-synthesized HMSM particles in controlled drug delivery was investigated by loading amoxicillin as an antibiotic compound with high entrapment efficiency (up to 46%). Furthermore, to improve the biocompatibility of the amoxicillin-loaded HMSM particles, their surfaces were functionalized with poly(allylamine hydrochloride) and alginate as biocompatible polymers via the layer-by-layer assembly. The resulting particles were evaluated toward Escherichia coli (Gram-negative) bacteria and indicated the bacterial inhibition up to 90% in less than 2 h. Finally, we explored the versatility of HMSMs as drug carriers for pancreatic cancer treatment. Because the pH value of the extracellular medium in pancreatic tumors is lower than that of the healthy tissue, chitosan as a pH-sensitive gatekeeper was grafted to the HMSM surface and then loaded with a pro-apoptotic NCL antagonist agent (N6L) as an anticancer drug. The obtained particles exhibited pH-responsive drug releases and excellent anticancer activities with inhibition of cancer cell growth up to 60%.

Abundance and distribution of small microplastics (≤ 3 µm) in sediments and seaworms from the Southern Mediterranean coasts and characterisation of their potential harmful effects.

Microplastics (MPs) are an uncontrolled contaminant affecting marine ecosystems. Studying their undesirable effects has been an attractive field for scientists in recent years. This study is the first to investigate the uptake and distribution of small microplastics (≤3 µm) from several sites in the Southern Mediterranean coasts. This work primarilyaims to provide a qualitative and quantitative analysis of microplastics in sediments as well as in the seaworms (Hediste diversicolor) from eight sites from the Tunisian coasts using Fourier transform infrared spectroscopy and Raman microspectroscopy. The second aim is to evaluate the potential toxic effects of environmental microplastics using a set of biomarkers such as Catalase, Glutathione-S-Transferase, Malondialdehyde and Acetylcholinesterase. Our findings showed that microplastics (1 mm-1.2 µm) were present in all sediments with its abundance ranging from 129 to 606 items kg-1. Microplastic accumulation in seaworms (3 µm-0.22 µm) was 0.5-3.7 items g-1. The predominant polymer was polyethylene. Results also revealed a significant variation among sites in the parameters associated with oxidative stress. Thus, size abundance of microplastics in seaworms was mainly correlated with oxidative stress biomarkers. Our data should be carefully considered in view of the microplastic presence with several types and sizes in Tunisian coastal sites, their potential toxic effects, and their transfer into food web.