Polysaccharides and proteins-based bionanocomposites for microencapsulation of probiotics to improve stability and viability in the gastrointestinal tract: A review.

Probiotics have recently received significant attention due to their various benefits, such as the modulation of gut flora, reduction of blood sugar and insulin resistance, prevention and treatment of digestive disorders, and strengthening of the immune system. One of the major issues concerning probiotics is the maintenance of their viability in the presence of digestive conditions and extended shelf life during storage. To address this concern, numerous techniques have been explored to achieve success. Among these methods, the microencapsulation of probiotics has been proposed as the most effective way to overcome this challenge. The combination of nanomaterials with biopolymer coating is considered a novel approach to improve its viability and effective delivery. The use of polysaccharides and proteins-based bionanocomposites for microencapsulation of probiotics has emerged as an efficient and promising approach for maintaining cell viability and targeted delivery. This review article aims to investigate the use of different bionanocomposites in microencapsulation of probiotics and their effect on cell survival in long-term storage and harsh conditions in the gastrointestinal tract.

Integrating gene expression data into a genome-scale metabolic model to identify reprogramming during adaptive evolution.

The development of a method for identifying latent reprogramming in gene expression data resulting from adaptive laboratory evolution (ALE) in response to genetic or environmental perturbations has been a challenge. In this study, a method called Metabolic Reprogramming Identifier (MRI), based on the integration of expression data to a genome-scale metabolic model has been developed. To identify key genes playing the main role in reprogramming, a MILP problem is presented and maximization of an adaptation score as a criterion indicating a pattern of using metabolism with maximum utilization of gene expression resources is defined as an objective function. Then, genes with complete expression usage and significant expression differences between wild-type and evolved strains were selected as key genes for reprogramming. This score is also applied to evaluate the compatibility of expression patterns with maximal use of key genes. The method was implemented to investigate the reprogramming of Escherichia coli during adaptive evolution caused by changing carbon sources. cyoC and cydB responsible for establishing proton gradient across the inner membrane were identified to be vital in the E. coli reprogramming when switching from glucose to lactate. These results indicate the importance of the inner membrane in reprogramming of E. coli to adapt to the new environment. The method predicts no reprogramming occurs during the evolution for growth on glycerol.

Inhibitory effect of plain and functionalized graphene nanoplateles on hen egg white lysozyme fibrillation.

Protein fibrillation is a phenomenon associated with misfolding and the production of highly ordered nanofibrils, which may cause serious degenerative diseases such as Parkinson's disease, Alzheimer's disease, and type 2 diabetes. Upon contact with biological fluids, the nanomaterials are immediately covered by proteins and interact with them. In this study, the effects of Graphene NanoPlateles (Plain-GNPs) and their modified forms with a carboxyl group (GNPs -COOH) and an amine group (GNPs -NH2) are evaluated on the fibrillation process of Hen Egg White Lysozyme (HEWL). The fibrillation process of HEWL was studied using thioflavin-T, Circular Dichroism spectrometry, and Atomic Force Microscopy. Plain-GNPs significantly decreased the fibrillation process at different stages, including nucleation, exponential fibrillation phases, and end-mature fibril products. However, GNPs-COOH and GNPs-NH2 affected the final fluorescence of ThT. The species formed in the presence of Plain-GNPs showed less toxicity in SH-SY5Y cells, which could be applicable for therapeutic purposes.

Role of bioactive magnetic nanoparticles in the prevention of wound pathogenic biofilm formation using smart nanocomposites.

BACKGROUND: Biofilm formation and its resistance to various antibiotics is a serious health problem in the treatment of wound infections. An ideal wound dressing should have characteristics such as protection of wound from microbial infection, suitable porosity (to absorb wound exudates), proper permeability (to maintain wound moisture), nontoxicity, and biocompatibility. Although silver nanoparticles (AgNPs) have been investigated as antimicrobial agents, their limitations in penetrating into the biofilm, affecting their efficiency, have consistently been an area for further research. RESULTS: Consequently, in this study, the optimal amounts of natural and synthetic polymers combination, along with AgNPs, accompanied by iron oxide nanoparticles (IONPs), were utilized to fabricate a smart bionanocomposite that meets all the requirements of an ideal wound dressing. Superparamagnetic IONPs (with the average size of 11.8 nm) were synthesized through co-precipitation method using oleic acid to improve their stability. It was found that the addition of IONPs to bionanocomposites had a synergistic effect on their antibacterial and antibiofilm properties. Cytotoxicity assay results showed that nanoparticles does not considerably affect eukaryotic cells compared to prokaryotic cells. Based on the images obtained by confocal laser scanning microscopy (CLSM), significant AgNPs release was observed when an external magnetic field (EMF) was applied to the bionanocomposites loaded with IONPs, which increased the antibacterial activity and inhibited the formation of biofilm significantly. CONCLUSION: These finding indicated that the nanocomposite recommended can have an efficient properties for the management of wounds through prevention and treatment of antibiotic-resistant biofilm.

Developing a metabolic model-based fed-batch feeding strategy for Pichia pastoris fermentation through fine-tuning of the methanol utilization pathway.

Pichia pastoris is a commonly used microbial host for recombinant protein production. It is mostly cultivated in fed-batch mode, in which the environment of the cell is continuously changing. Hence, it is vital to understand the influence of feeding strategy parameters on the intracellular reaction network to fine-tune bioreactor performance. This study used dynamic flux balance analysis (DFBA) integrated with transcriptomics data to simulate the recombinant P. pastoris (Muts ) growth during the induction phase for three fed-batch strategies, conducted at constant specific growth rates (µ-stat). The induction phase was split into equal time intervals, and the correlated reactions with protein yield were identified in the three fed-batch strategies using the Pearson correlation coefficient. Subsequently, principal component analysis (PCA) was applied to cluster induction phase time intervals and identify the role of correlated reactions on metabolic differentiation of time intervals. It was found that increasing fluxes through the methanol dissimilation pathway increased protein yield. By adding a methanol assimilation pathway inhibitor (HgCl2 ) to the shake flask medium growing on glycerol: methanol mixture (10%: 90%, v/v), the protein titre increased by 60%. As per DFBA, the higher the methanol to biomass flux ratio (Rmeoh/Δx ), the higher the protein yield. Finally, a novel feeding strategy was developed to increase the amount of Rmeoh/Δx compared to the three feeding strategies. The concentration of recombinant human growth hormone (rhGH), used as the model protein, increased by 16% compared to the optimal culture result obtained previously (800 mg L-1 to 928 mg L-1 ), while production yield improved by 85% (24.8 mg gDCW -1 to 46 mg gDCW -1 ).

Rapid generation of homogenous tumor spheroid microtissues in a scaffold-free platform for high-throughput screening of a novel combination nanomedicine.

Combination nanomedicine is a potent strategy for cancer treatment. Exploiting different mechanisms of action, a novel triple drug delivery system of 5-fluorouracil, curcumin, and piperine co-loaded human serum albumin nanoparticles (5FU-CUR-PIP-HSA-NPs) was developed via the self-assembly method for suppressing breast tumor. Both hydrophobic and hydrophilic drugs were successfully encapsulated in the HSA NPs with a high drug loading efficiency (DLE) of 10%. Successful clinical translation of nanomedicines, however, is a challenging process requiring considerable preclinical in vitro and in vivo animal tests. The aim of this study was to develop a homemade preclinical 3D culture model in the standard 96-well plates in a cost and time-effective novel approach for the rapid generation of homogenous compact tumor spheroids for disease modeling, and anticancer therapeutic/nanomedicine screening. The knowledge of drug screening can be enhanced by employing such a model in a high-throughput manner. Accordingly, to validate the formulated drug delivery system and investigate the cellular uptake and cytotoxicity effect of the nanoformulation, 3D tumor spheroids were employed. The practicality of the nanomedicine system was substantiated in different tests. The in vitro uptake of the NPs into the tight 3D tumor spheroids was facilitated by the semi-spherical shape of the NPs with a proper size and surface charge. 5FU-CUR-PIP-HSA-NPs demonstrated high potency of migration inhibition as a part of successful anti-metastatic therapy as well. The remarkable differences in 2D and 3D cytotoxicities emphasize the importance of employing 3D tumor models as an intermediate step prior to in vivo animal experiments for drug/nanomedicine screening.

Green synthesis of bovine serum albumin/oxidized gum Arabic nanocomposite as pH-responsive carrier for controlled release of piperine and the molecular docking study.

A safe drug carrier was synthesized by albumin (BSA) and oxidized gum arabic (OGA). Piperine (PIP) was loaded into BSA/OGA nanobiocomposites by desolvation method. A set of experiments were designed by considering different contents of OGA (5, 7.5 and 10 mg) and PIP (1 and 2 mg). The presence of the band at 1600-1660 cm-1 in FTIR spectra revealed the successful interaction between OGA and BSA. PIP2-BSA/OGA5 was selected as a suitable carrier due to its smaller size (<300 nm) and higher loading efficiency (1.5 ± 0.2 %). The encapsulation efficiency of PIP into BSA/OGA5 was 57.6 ± 2 %. The average size, polydispersity index and zeta potential of PIP2-BSA/OGA5 were 292 ± 4.4 nm, 0.185 ± 0.03 and - 24.4 ± 1.7 mV, respectively. SEM and TEM images proved the formation of spherical-shaped nanoparticles. The disappearance of endothermic peak belonging to free PIP in DSC thermogram of PIP2-BSA/OGA5 evidenced its encapsulation into carrier. PIP2-BSA/OGA5 exhibited the sustained drug release. The cell viability of MCF-7 cells after 48 h exposure to BSA/OGA5, PIP2-BSA/OGA5 and free PIP was reported 90 %, 40.1 % and 30.6 %, respectively. The molecular docking study reported that the binding affinity of PIP for BSA/OGA nanocomposite was -8.7 kcal/mol indicating the acceptable stability of the prepared drug carrier.

Reconstruction of a generic genome-scale metabolic network for chicken: Investigating network connectivity and finding potential biomarkers.

Chicken is the first sequenced avian that has a crucial role in human life for its meat and egg production. Because of various metabolic disorders, study the metabolism of chicken cell is important. Herein, the first genome-scale metabolic model of a chicken cell named iES1300, consists of 2427 reactions, 2569 metabolites, and 1300 genes, was reconstructed manually based on KEGG, BiGG, CHEBI, UNIPROT, REACTOME, and MetaNetX databases. Interactions of metabolic genes for growth were examined for E. coli, S. cerevisiae, human, and chicken metabolic models. The results indicated robustness to genetic manipulation for iES1300 similar to the results for human. iES1300 was integrated with transcriptomics data using algorithms and Principal Component Analysis was applied to compare context-specific models of the normal, tumor, lean and fat cell lines. It was found that the normal model has notable metabolic flexibility in the utilization of various metabolic pathways, especially in metabolic pathways of the carbohydrate metabolism, compared to the others. It was also concluded that the fat and tumor models have similar growth metabolisms and the lean chicken model has a more active lipid and carbohydrate metabolism.

Valine feeding reduces ammonia production through rearrangement of metabolic fluxes in central carbon metabolism of CHO cells.

Ammonia is a toxic byproduct of CHO cell metabolism, which inhibits cell growth, reduces cell viability, alters glycosylation, and decreases recombinant protein productivity. In an attempt to minimize the ammonium accumulation in cell culture media, different amino acids were added individually to the culture medium before the production phase to alleviate the negative effects of ammonium on cell culture performance. Among all the amino acids examined in this study, valine showed the most positive impact on CHO cell culture performance. When the cultured CHO cells were fed with 5 mM valine, EPO titer was increased by 25% compared to the control medium, and ammonium and lactate production were decreased by 23 and 26%, respectively, relative to the control culture. Moreover, the sialic acid content of the EPO protein in valine-fed culture was higher than in the control culture, most likely because of the lower ammonium concentration. Flux balance analysis (FBA) results demonstrated that the citric acid cycle was enriched by valine feeding. The measurement of TCA cycle activity supported this finding. The analysis revealed that there might be a link between promoting tricarboxylic acid (TCA) cycle metabolism in valine-fed culture and reduction in lactate and ammonia accumulation. Furthermore, in valine-fed culture, FBA outcomes showed that alanine was excreted into the medium as the primary mechanism for reducing ammonium concentration. It was predicted that the elevated TCA cycle metabolism was concurrent with an increment in recombinant protein production. Taken together, our data demonstrate that valine addition could be an effective strategy for mitigating the negative impacts of ammonium and enhancing glycoprotein production in both quality and quantity. KEY POINTS: • Valine feeding can mitigate the negative impacts of ammonia on CHO cell growth. • Valine addition assists the ammonia removal mechanism by enriching the TCA cycle. • Ammonia is removed from the media through alanine excretion in valine-fed culture.

Increasing-Aeration Strategy: a Practical Approach to Enhance the Schizophyllan Production and Improve the Operational Conditions of Schizophyllum commune Cultivation in the Stirred Tank and Bubble Column Bioreactors.

In the present study, the effect of employing the increasing- aeration strategy (IAS) in the oxygen-limited situation and proportionate to increasing oxygen demand of the fungus Schizophyllum commune (S. commune) has been investigated in both stirred tank (STB) and bubble column (BCB) bioreactors. The purpose was to enhance schizophyllan (SPG) production by preventing oxygen starvation, improve mixing conditions of pseudoplastic culture, and intensify shear stress on fungus pellets to release SPG. At first, a constant-aeration rate of 0.08 vvm was implemented in both bioreactors to evaluate the new strategy compared to the previously studied methods. In the second set of experiments with IAS, along with the increasing oxygen demand of culture, the inlet airflow was increased gradually, while the dissolved oxygen (DO) was maintained higher than zero and below 1%. Using IAS in STB significantly raised productivity by about 100% in 96 h from 0.035 to 0.073 g/L.h. Also, employing this strategy in BCB led to a 30% increase in the maximum SPG production from 3.2 to 4.2 g/L. IAS can effectively help handle the operation of S. commune cultivation on a large scale by improving mixing conditions, mass transfer, and shear stress in both bioreactor types. This method had a significant impact on STB cultivation and its productivity so that it can be a practical approach to SPG's industrial production.

A Protein Corona Modulates Interactions of α-Synuclein with Nanoparticles and Alters the Rates of the Microscopic Steps of Amyloid Formation.

Nanoparticles (NPs) can modulate protein aggregation and fibril formation in the context of amyloid diseases. Understanding the mechanism of this action remains a critical next step in developing nanomedicines for the treatment or prevention of Parkinson's disease. α-Synuclein (α-Syn) can undergo interactions of different strength with nanoparticles, and these interactions can be prevented by the presence of a protein corona (PC) acquired during the exposure of NPs to serum proteins. Here, we develop a method to attach the PC irreversibly to the NPs, which enables us to study in detail the interaction of α-Syn and polyethylenimine-coated carboxyl-modified polystyrene NPs (PsNPs-PEI) and the role of the dynamics of the interactions. Analysis of the kinetics of fibril formation reveals that the NPs surface promotes the primary nucleation step of amyloid fibril formation without significantly affecting the elongation and fragmentation steps or the final equilibrium. Furthermore, the results show that even though α-Syn can access the surface of NPs that are precoated with a PC, due to the dynamic nature of the PC proteins, the PC nevertheless reduces the acceleratoring effect of the NPs. This effect is likely to be caused by reducing the overall amount of weakly interacting α-Syn molecules on the NP surface and the access of further α-Syn required for fibril elongation. Our experimental approach provides microscopic insight into how serum proteins can modulate the complex interplay between NPs and amyloid proteins.

Highly efficient porous magnetic polydopamine/copper phosphate with three-dimensional hierarchical nanoflower morphology as a selective platform for recombinant proteins separation.

The separation and purification of recombinant pharmaceutical proteins is a fundamental and challenging step in the biotechnology industry. Hierarchical nanostructures with unique features and high stability can be used as efficient adsorbents. In this study, hierarchical magnetic polydopamine-copper phosphate nanoflowers (Cu-PDA MNFs) were synthesized as high-performance magnetic adsorbents in a simple and low-cost method based on green chemistry. The prepared hybrid Cu-PDA MNFs revealed great performance for separating pure recombinant human growth hormone (rhGH) and the rhGH acquired from recombinant Pichia pastoris yeast fermentation. The analysis confirmed that Cu-PDA MNFs exhibited a high adsorption capacity of 257.4 mg rhGH g-1 Cu-PDA MNFs and a fast adsorption rate for approaching the adsorption equilibrium within less than 30 min with a recovery efficiency of 74% of rhGH from the real sample. In addition, recycling tests demonstrated the stability and recyclability of Cu-PDA MNFs for at least six cycles with almost constant adsorption capacity and no toxicity. Based on these results, Cu-PDA MNFs could be considered as a promising candidate for separation and purification of rhGH. This work presents a new approach to using organic-inorganic nanoflowers as the hierarchical nanostructure for purification of pharmaceutical proteins with high performance.

Living Lactobacillus-ZnO nanoparticles hybrids as antimicrobial and antibiofilm coatings for wound dressing application.

Probiotic bacteria are able to produce antimicrobial substances as well as to synthesize green metal nanoparticles (NPs). New antimicrobial and antibiofilm coatings (LAB-ZnO NPs), composed of Lactobacillus strains and green ZnO NPs, were employed for the modification of gum Arabic-polyvinyl alcohol-polycaprolactone nanofibers matrix (GA-PVA-PCL) against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. The physicochemical properties of ZnO NPs biologically synthesized by L. plantarum and L. acidophilus, LAB-ZnO NPs hybrids and LAB-ZnO NPs@GA-PVA-PCL were studied using FE-SEM, EDX, EM, FTIR, XRD and ICP-OES. The morphology of LAB-ZnO NPs hybrids was spherical in range of 4.56-91.61 nm with an average diameter about 34 nm. The electrospun GA-PVA-PCL had regular, continuous and without beads morphology in the scale of nanometer and micrometer with an average diameter of 565 nm. Interestingly, the LAB not only acted as a biosynthesizer in the green synthesis of ZnO NPs but also synergistically enhanced the antimicrobial and antibiofilm efficacy of LAB-ZnO NPs@GA-PVA-PCL. Moreover, the low cytotoxicity of ZnO NPs and ZnO NPs@GA-PVA-PCL on the mouse embryonic fibroblasts cell line led to make them biocompatible. These results suggest that LAB-ZnO NPs@GA-PVA-PCL has potential as a safe promising antimicrobial and antibiofilm dressing in wound healing against pathogens.

Synergisms of machine learning and constraint-based modeling of metabolism for analysis and optimization of fermentation parameters.

Recent noteworthy advances in developing high-performing microbial and mammalian strains have enabled the sustainable production of bio-economically valuable substances such as bio-compounds, biofuels, and biopharmaceuticals. However, to obtain an industrially viable mass-production scheme, much time and effort are required. The robust and rational design of fermentation processes requires analysis and optimization of different extracellular conditions and medium components, which have a massive effect on growth and productivity. In this regard, knowledge- and data-driven modeling methods have received much attention. Constraint-based modeling (CBM) is a knowledge-driven mathematical approach that has been widely used in fermentation analysis and optimization due to its ability to predict the cellular phenotype from genotype through high-throughput means. On the other hand, machine learning (ML) is a data-driven statistical method that identifies the data patterns within sophisticated biological systems and processes, where there is inadequate knowledge to represent underlying mechanisms. Furthermore, ML models are becoming a viable complement to constraint-based models in a reciprocal manner when one is used as a pre-step of another. As a result, a more predictable model is produced. This review highlights the applications of CBM and ML independently and the combination of these two approaches for analyzing and optimizing fermentation parameters.

High cell density culture of recombinant E. coli in the miniaturized bubble columns.

Miniaturized bubble columns (MBCs) can provide mass transfer characteristics similar to stirred tank bioreactors. In this study, a new application was developed for MBCs to investigate the effect of feeding strategy and medium type on the fed-batch culture of recombinant E. coli. The results showed that the exponential feeding strategy and defined M9 medium were more suitable to achieve the high cell density culture (HCDC). The maximum obtained cell concentration in exponential feeding strategy in the defined medium without induction, was at OD600 of 169, while glucose concentration was maintained under 2 g/L. To the best of our knowledge, this cell concentration cannot be achieved in lab or pilot scale bubble columns. At the end of the process, adverse effect of the metabolic burden due to induction and mass transfer limitations decreased the obtained final cell concentration to OD600 of 116. Finally, a comparison of the results for fed-batch culture in the stirred tank bioreactor with those of the MBCs showed that their lower cell concentrations were due to the hydrodynamics limitations of MBCs. Yet, it was found that the MBCs are efficient tools in development of feeding strategies and evaluation of medium components for HCDC of recombinant E. coli.

An integrated modular framework for modeling the effect of ammonium on the sialylation process of monoclonal antibodies produced by CHO cells.

BACKGROUND: Monoclonal antibodies (mABs) have emerged as one of the most important therapeutic recombinant proteins in the pharmaceutical industry. Their immunogenicity and therapeutic efficacy are influenced by post-translational modifications, specifically the glycosylation process. Bioprocess conditions can influence the intracellular process of glycosylation. Among all the process conditions that have been recognized to affect the mAB glycoforms, the detailed mechanism underlying how ammonium could perturb glycosylation remains to be fully understood. It was shown that ammonium induces heterogeneity in protein glycosylation by altering the sialic acid content of glycoproteins. Hence, understanding this mechanism would aid pharmaceutical manufacturers to ensure consistent protein glycosylation. METHODS: Three different mechanisms have been proposed to explain how ammonium influences the sialylation process. In the first, the inhibition of CMP-sialic acid transporter, which transports CMP-sialic acid (sialylation substrate) into the Golgi, by an increase in UDP-GlcNAc content that is brought about by the augmented incorporation of ammonium into glucosamine formation. In the second, ammonia diffuses into the Golgi and raises its pH, thereby decreasing the sialyltransferase enzyme activity. In the third, the reduction of sialyltransferase enzyme expression level in the presence of ammonium. We employed these mechanisms in a novel integrated modular platform to link dynamic alteration in mAB sialylation process with extracellular ammonium concentration to elucidate how ammonium alters the sialic acid content of glycoproteins. RESULTS: Our results show that the sialylation reaction rate is insensitive to the first mechanism. At low ammonium concentration, the second mechanism is the controlling mechanism in mAB sialylation and by increasing the ammonium level (< 8 mM) the third mechanism becomes the controlling mechanism. At higher ammonium concentrations (> 8 mM) the second mechanism becomes predominant again. CONCLUSION: The presented model in this study provides a connection between extracellular ammonium and the monoclonal antibody sialylation process. This computational tool could help scientists to develop and formulate cell culture media. The model illustrated here can assist the researchers to select culture media that ensure consistent mAB sialylation.

Pectin/lignocellulose nanofibers/chitin nanofibers bionanocomposite as an efficient biosorbent of cholesterol and bile salts.

A new biosorbent Ca-crosslinked pectin/lignocellulose nanofibers/chitin nanofibers (PLCN) was synthesized for cholesterol and bile salts adsorption from simulated intestinal fluid during gastric-intestinal passage. The physico-chemical properties of PLCN were studied using SEM, FTIR, XRD, DSC and BET. Before gastrointestinal passage, PLCN had an amorphous single-phase, compact structure formed via hydrogen and van der Waals bonds that revealed an irregular shape with the shriveled surface but watery condition and enzymatic digestion led to create a porous structure without destruction because of the water-insoluble nanofibers, therefore increasing the adsorption capacity. The maximum adsorption capacity reached 37.9 and 5578.4 mg/g for cholesterol and bile salts, respectively. Freundlich isotherm model indicated the reversible heterogeneous adsorption of both cholesterol and bile salts on PLCN. Further, their adsorption followed pseudo-second order kinetic model. These results suggest that PLCN has potential as a gastrointestinal-resistant biosorbent for cholesterol and bile salts adsorption applicable in medicine and food industry.

Repetitive non-destructive extraction of lipids from Chlorella vulgaris grown under stress conditions.

The aim of this study was the investigation of non-destructive lipid extraction from Chlorella vulgaris grown under stress conditions of nutrient limitation and salinity. To select a suitable solvent for extraction, the performances of decane, dodecane and hexadecane were tested based on their effect on lipid extraction and cell viability. The results showed that dodecane was the most suitable solvent for the extraction process. The concentration of extracted lipids from stressed cells was 2762.52 ± 11.38 mg L-1, i.e. a value 1.75 times higher than that obtained from unstressed cells. Long-term extraction was also evaluated with continuous dodecane recirculation during five-stage extraction and a recovery time of 24 h between the extraction steps, which yielded after the fifth extraction stage a total lipid amount as high as 9811.56 mg L-1. These results showed that non-destructive lipid recovery can be effectively performed by applying stress conditions and in repetitive extractions.

A novel self-assembled micelles based on stearic acid modified schizophyllan for efficient delivery of paclitaxel.

This study was aimed to design a novel amphiphilic carrier based on schizophyllan (SPG) exopolysacharide for drug delivery. Stearic acid (SA) was used for the esterification of SPG with two degrees of substitutions (SA-SPG0.5 and SA-SPG1). The H NMR and FTIR spectroscopies verified the succesfull esterification of SPG. The polymeric micelles easily self-assembled into nanomicelles by ultrasound method. Fluorescence spectroscopy showed that the critical micelle concentrations (CMCs) of SA-SPG0.5 and SA-SPG1 micelles were 0.068 mg/mL and 0.027 mg/mL, respectively. DLS analyses showed that nanomicelles were ranged from 156 to 175 nm. SEM and TEM images showed that nanomicelles were mostly spherical. Paclitaxel (PTX) as a drug model was successfully loaded into SA-SPG nanomicelles with three different drug/polymer weight ratios of 0.1, 0.2 and 0.3. The highest encapsulation efficiency (75 %) was obtained when the PTX/SA-SPG weight ratio was 0.1. The in vitro release of PTX from SA-SPG micelles represented the sustained release profile over 144 h. MTT assay showed that the PTX-loaded SA-SPG nanomicelles had the higher cytotoxicity against MCF-7 cells than free PTX. These results revealed that the synthesized SA-SPG nanomicelles had a promising potential as a new carrier for efficient delivery of hydrophobic drugs.

Synthesis and characterization of Schiff base containing bovine serum albumin-gum arabic aldehyde hybrid nanogels via inverse miniemulsion for delivery of anticancer drug.

The periodate modified gum arabic was used as a natural-based, non-toxic cross-linker to synthesize hybrid bovine serum albumin-gum arabic aldehyde (BSA-GAA) nanogels by Schiff base reaction through the inverse miniemulsion method for the first time. The synthesis process was performed in the absence of toxic organic solvents using fractionated coconut oil as the continuous phase. The particle size of the nanogels was managed by tweaking the concentration of the surfactants (Span 80/Tween 80) and the total volume of the aqueous phase. Based on the bicinchoninic acid method, the cross-linking efficiency of BSA and GAA was estimated at 98%. 5-fluorouracil (5-FU) was selected as the sample drug. The 5-FU-loaded hybrid nanogels showed a spherical morphology with an average diameter of 231.33 ±12.74 nm and a zeta potential of -31.6 mV. The encapsulation and loading efficiency of the nanogels were calculated at 42 ± 4.52% and 2.37 ± 0.59%, respectively. The properties of the hybrid nanogels were analyzed by dynamic light scattering (DLS), Fourier transform infrared microscopy (FTIR) analysis, field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). The pH sensitivity of the hybrid nanogels was confirmed by the in vitro release profiles of 5-FU in different buffers. Hemolysis assay revealed the in vitro hemocompatibility of the hybrid nanogels which inhibited the growth of MCF-7 cells with an IC50 value of 16.21 µM. The present study suggested that these biobased hybrid nanogels could have a great potential in drug delivery and other biomedical applications.