Metagenomic dissection of the intestinal microbiome in the giant river prawn Macrobrachium rosenbergii infected with Decapod iridescent virus 1.

Microbiome in the intestines of aquatic invertebrates plays pivotal roles in maintaining intestinal homeostasis, especially when the host is exposed to pathogen invasion. Decapod iridescent virus 1 (DIV1) is a devastating virus seriously affecting the productivity and success of crustacean aquaculture. In this study, a metagenomic analysis was conducted to investigate the genomic sequences, community structure and functional characteristics of the intestinal microbiome in the giant river prawn Macrobrachiumrosenbergii infected with DIV1. The results showed that DIV1 infection could significantly reduce the diversity and richness of intestinal microbiome. Proteobacteria represented the largest taxon at the phylum level, and at the species level, the abundance of Gonapodya prolifera and Solemya velum gill symbiont increased significantly following DIV1 infection. In the infected prawns, four metabolic pathways related to purine metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and pentose phosphate pathway, and five pathways related to nucleotide excision repair, homologous recombination, mismatch repair, base excision repair, and DNA replication were significantly enriched. Moreover, several immune response related pathways, such as shigellosis, bacterial invasion of epithelial cells, Salmonella infection, and Vibrio cholerae infection were repressed, indicating that secondary infection in M. rosenbergii may be inhibited via the suppression of these immune related pathways. DIV1 infection led to the induction of microbial carbohydrate enzymes such as the glycoside hydrolases (GHs), and reduced the abundance and number of antibiotic-resistant ontologies (AROs). A variety of AROs were identified from the microbiota, and mdtF and lrfA appeared as the dominant genes in the detected AROs. In addition, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration were the main antibiotic resistance mechanisms. Collectively, the data would enable a deeper understanding of the molecular response of intestinal microbiota to DIV1, and offer more insights into its roles in prawn resistance to DIVI infection.

The Carbonic Anhydrase ßCA1 Functions in PopW-Mediated Plant Defense Responses in Tomato.

ß-Carbonic anhydrase (ßCA) is very important for plant growth and development, but its function in immunity has also been examined. In this study, we found that the expression level of Solanum lycopersicum ßCA1 (SlßCA1) was significantly upregulated in plants treated with Xanthomonas euvesicatoria 85-10. The protein was localized in the nucleus, cell membrane and chloroplast. Using tomato plants silenced with SlßCA1, we demonstrated that SlßCA1 plays an active role in plant disease resistance. Moreover, we found that the elicitor PopW upregulated the expression of SlßCA1, while the microbe-associated molecular pattern response induced by PopW was inhibited in TRV-SlßCA1. The interaction between PopW and SlßCA1 was confirmed. Here, we found that SlßCA1 was positively regulated during PopW-induced resistance to Xanthomonas euvesicatoria 85-10. These data indicate the importance of SlßCA1 in plant basic immunity and its recognition by the Harpin protein PopW as a new target for elicitor recognition.

Bio-Inspired Nanocarriers Derived from Stem Cells and Their Extracellular Vesicles for Targeted Drug Delivery.

With their seemingly limitless capacity for self-improvement, stem cells have a wide range of potential uses in the medical field. Stem-cell-secreted extracellular vesicles (EVs), as paracrine components of stem cells, are natural nanoscale particles that transport a variety of biological molecules and facilitate cell-to-cell communication which have been also widely used for targeted drug delivery. These nanocarriers exhibit inherent advantages, such as strong cell or tissue targeting and low immunogenicity, which synthetic nanocarriers lack. However, despite the tremendous therapeutic potential of stem cells and EVs, their further clinical application is still limited by low yield and a lack of standardized isolation and purification protocols. In recent years, inspired by the concept of biomimetics, a new approach to biomimetic nanocarriers for drug delivery has been developed through combining nanotechnology and bioengineering. This article reviews the application of biomimetic nanocarriers derived from stem cells and their EVs in targeted drug delivery and discusses their advantages and challenges in order to stimulate future research.

Dynamic N6-methyladenosine RNA methylation landscapes reveal epi-transcriptomic modulation induced by ammonia nitrogen exposure in the Pacific whiteleg shrimp Litopenaeus vannamei.

Despite the versatility of RNA m6A methylation in regulating various biological processes, its involvement in the physiological response to ammonia nitrogen toxicity in decapod crustaceans like shrimp remains enigmatic. Here, we provided the first characterization of dynamic RNA m6A methylation landscapes induced by toxic ammonia exposure in the Pacific whiteleg shrimp Litopenaeus vannamei. The global m6A methylation level showed significant decrease following ammonia exposure, and most of the m6A methyltransferases and m6A binding proteins were significantly repressed. Distinct from many well-studied model organisms, m6A methylated peaks in the transcriptome of L. vannamei were enriched not only near the termination codon and in the 3' untranslated region (UTR), but also around the start codon and in the 5' UTR. Upon ammonia exposure, 11,430 m6A peaks corresponding to 6113 genes were hypo-methylated, and 5660 m6A peaks from 3912 genes were hyper-methylated. The differentially methylated genes showing significant changes in expression were over-represented by genes associated with metabolism, cellular immune defense and apoptotic signaling pathways. Notably, the m6A-modified ammonia-responsive genes encompassed a subset of genes related to glutamine synthesis, purine conversion and urea production, implying that m6A methylation may modulate shrimp ammonia stress responses partly through these ammonia metabolic processes.

Pluronic F127 coating performance on PLGA nanoparticles: Enhanced flocculation and instability.

Nanoparticles (NPs) can be incorporated into hydrogels to obtain multifunctional hybrid systems to meet the delivery needs of different drugs. However, the stability of NPs in hydrogels is rarely revealed. In this article, we tried to explore the underlying mechanism of an interesting phenomenon that poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PNPs) could flocculate and deposit in Pluronic F127 (F127) hydrogels at 4 °C. The results showed that this flocculation was relevant to the type of emulsifier formulated in PNPs, the particle materials and the F127 concentration, but independent of PLGA polymer end groups. Exactly, PNPs containing polyvinyl alcohol (PVA) as the emulsifier flocculated in F127 solution with a concentration above 15 %. The flocculated PNPs possessed increased particle size, decreased zeta potential, reduced hydrophobicity and an obvious coating layer, and these characteristics could be restored almost to the original state after two washes of flocculated PNPs with water. Moreover, the flocculation had no impact on the long-term size stability and drug-loading capacity of PNPs, and F127-treated PNPs showed improved cellular uptake than untreated PNPs. These results provide the evidence that adsorption of high concentrations of F127 on the surface of PNPs/PVA may lead to flocculation, and the flocculation is reversible by simply washing the flocs with water. To the best of our knowledge, this is the first study to scientifically explore the stability of PNPs in F127 hydrogels, providing theoretical and experimental support for the rational design and further development of nanoparticle-hydrogel composite.

A Report of Pectobacterium carotovorum subsp. actinidiae Causing Kiwifruit Bacterial Canker in Guangxi, China.

A bacterial pathogen strain was isolated from susceptible tissue of Hongyang variety kiwifruit in Zhongfeng Town, Ziyuan County, Guilin City, Guangxi, China. Due to the relatively single variety of kiwifruit in Guangxi, the control technology of fruit farmers is backward, and the climate is humid, which is suitable for the growth of pathogenic bacteria, resulting in frequent occurrence of diseases. In this study, the pathogen strain was identified based on morphological, physiological, and biochemical tests; 16S rRNA gene; PCR detection with specific primers; and Biolog analysis. The results showed that a tobacco allergic reaction could be induced by inoculation with the pathogenic bacteria. Additionally, brown necrotic plaques appeared on kiwifruit leaves, necrotic phloem lesions appeared, and wounds on kiwifruit branches turned brown. The characteristics identified by morphological, physiological, biochemical, and Biolog identification were similar to those caused by Pectobacterium sp. Through 16S rRNA gene sequence analysis and PCR identification with specific primers, bands with a size corresponding to target bands indicated that the pathogen was Pectobacterium carotovorum subsp. actinidiae. This is the first report of kiwifruit canker disease caused by P. carotovorum subsp. actinidiae in Guangxi, China. In addition, through this study, a preliminary understanding of the pathogen has been obtained, which will lay the foundation for the prevention and control of the disease in the future.

A Bacillus licheniformis Glycoside Hydrolase 43 Protein Is Recognized as a MAMP.

Glycoside hydrolases from pathogens have often been reported as inducers of immune responses. However, the roles of glycoside hydrolase from plant-growth-promoting rhizobacteria (PGPR) in the resistance of plants against pathogens is not well studied. In this study, we identified a glycoside hydrolase 43 protein, H1AD43, produced by Bacillus licheniformis BL06 that can trigger defense responses, including cell death. Ion-exchange and size-exclusion chromatography were used for separation, and the amino acid sequence was identified by mass spectrometry. The recombinant protein generated by prokaryotic expression was able to elicit a hypersensitive response (HR) in Nicotiana benthamiana and trigger early defense responses, including reactive oxygen species (ROS) burst, callose accumulation, and the induction of defense genes. In addition, the protein could induce resistance in N. benthamiana, in which it inhibited infection by Phytophthora capsici Leonian and tobacco mosaic virus-green fluorescent protein (TMV-GFP) expression. H1AD43 thus represents a microbe-associated molecular pattern (MAMP) of PGPR that induces plant disease resistance and may provide a new method for the biological control of plant disease.

Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics.

Inflammation is a beneficial and physiological process, but there are a number of inflammatory diseases which have detrimental effects on the body. In addition, the drugs used to treat inflammation have toxic side effects when used over a long period of time. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can be isolated from a variety of tissues and can be differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for the treatment of inflammatory diseases. The therapeutic potential of MSCs is currently being investigated for various inflammatory diseases, such as kidney injury, lung injury, osteoarthritis (OA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSCs can perform multiple functions, including immunomodulation, homing, and differentiation, to enable damaged tissues to form a balanced inflammatory and regenerative microenvironment under severe inflammatory conditions. In addition, accumulated evidence indicates that exosomes from extracellular vesicles of MSCs (MSC-Exos) play an extraordinary role, mainly by transferring their components to recipient cells. In this review, we summarize the mechanism and clinical trials of MSCs and MSC-Exos in various inflammatory diseases in detail, with a view to contributing to the treatment of MSCs and MSC-Exos in inflammatory diseases.

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis.

Purpose: Mesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity. Hence, specific co-delivery of "anti-inflammatory/anti-fibrosis" drugs to the glomerular mesangial cell (MC) region is expected to produce better therapeutic effects. Methods: A novel kidney-targeted nanocarrier drug delivery system targeting MCs was constructed using passive targeting resulting from the difference in pore size between the glomerular endothelial layer and the basement membrane, and active targeting based on the specific binding of antibodies and antigens. Specifically, a liposome-nanoparticle hybrid (PLGA-LNHy) was formed by coating the surface of PLGA nanoparticles (NPs) with a phospholipid bilayer, and then PLGA-LNHy was co-modified with PEG and α8 integrin antibodies to obtain PLGA immunoliposomes (PLGA-ILs). Results: The results showed that the obtained NPs had a core-shell structure, uniform and suitable particle size (119.1 ± 2.31 nm), low cytotoxicity, and good mesangial cell-entry ability, which can successfully accumulate in the glomerular MC region. Both dexamethasone (DXMS) and captopril (CAP) were loaded onto PLGA-ILs with a drug loading of 10.22 ± 1.00% for DXMS and 6.37 ± 0.25% for CAP (DXMS/CAP@PLGA-ILs). In vivo pharmacodynamics showed that DXMS/CAP@PLGA-ILs can effectively improve the pathological changes in the mesangial area and positive expression of proliferating cell nuclear antigen (PCNA) in glomeruli as well as reduce the expression of inflammatory factors, fibrotic factors and reactive oxygen species (ROS). Thus, renal inflammation and fibrosis were relieved. Conclusion: We have provided a strategy to increase nanoparticle accumulation in MCs with the potential to implement regulatory effects of anti-inflammatory and anti-fibrosis in glomerulonephritis (GN).

Mesenchymal stem cells, exosomes and exosome-mimics as smart drug carriers for targeted cancer therapy.

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity to differentiate into several cell types under appropriate conditions. They also possess remarkable antitumor features that make them a novel choice to treat cancers. Accumulating evidence suggest that the MSCs-derived extracellular vesicles, known as exosomes, play an essential role in the therapeutic effects of MSCs mainly by carrying biologically active factors. However, limitations such as low yield of exosomes and difficulty in isolation and purification hinder their clinical applications. To overcome these issues, research on development of exosome-mimics has attracted great attention. This systematic review represents, to the best of our knowledge, the first thorough evaluations of the innate antineoplastic features of MSCs-derived exosomes or exosome-mimics, the methods of drug loading, application as drug delivery system and their impacts on targeted cancer therapy. Importantly, we dissect the commonalities and differences as well as address the shortcomings of work accumulated over the last two decades and discuss how this information can serve as a guide map for optimal experimental design implementation ultimately aiding the effective transition into clinical trials.

Dual-Regulated Functionalized Liposome-Nanoparticle Hybrids Loaded with Dexamethasone/TGFß1-siRNA for Targeted Therapy of Glomerulonephritis.

Mesangial cell (MC)-mediated glomerulonephritis is a frequent cause of end-stage renal disease, with immune inflammatory damage and fibrosis as its basic pathological processes. However, the treatment of glomerulonephritis remains challenging owing to limited drug accumulation and serious side effects. Hence, the specific codelivery of "anti-inflammatory/antifibrosis" drugs to the glomerular MC region is expected to yield better therapeutic effects. In this study, liposome-nanoparticle hybrids (Au-LNHy) were formed by coating the surface of gold nanoparticles with a phospholipid bilayer; the Au-LNHys formed were comodified with PEG and α8 integrin antibodies to obtain gold nanoparticle immunoliposomes (Au-ILs). Next, the Au-ILs were loaded with dexamethasone and TGFß1 siRNA to obtain DXMS/siRNA@Au-ILs. Our results showed that the functionalized nanoparticles had a core-shell structure, a uniform and suitable particle size, low cytotoxicity, and good MC entry, and lysosomal escape abilities. The nanoparticles were found to exhibit enhanced retention in glomerular MCs due to anti-α8 integrin antibody mediation. In vivo and in vitro pharmacodynamic studies showed the enhanced efficacy of DXMS/siRNA@Au-ILs modified with α8 integrin antibodies in the treatment of glomerulonephritis. In addition, DXMS/siRNA@Au-ILs were capable of effectively reducing the expression levels of TNF-α, TGF-ß1, and other cytokines, thereby improving pathological inflammatory and fibrotic conditions in the kidney, and significantly mediating the dual regulation of inflammation and fibrosis. In summary, our results demonstrated that effectively targeting the MCs of the glomerulus for drug delivery can inhibit local inflammation and fibrosis and produce better therapeutic effects, providing a new strategy and promising therapeutic approach for the development of targeted therapies for glomerular diseases.

Chitosan-poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor benefit for antibacterial and wound healing.

Chitosan/poloxamer-based thermosensitive hydrogels containing zinc gluconate/recombinant human epidermal growth factor (ZnG/rhEGF@Chit/Polo) were developed as a convenient, safe and effective dressing for skin wound treatment. Their fabrication procedure and characterization were reported, and their morphology was examined by a scanning electron microscope. Antibacterial and biofilms activities were evaluated by in vitro tests to reveal the inhibitory effects and scavenging activity on the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. ZnG/rhEGF@Chit/Polo was also investigated as a potential therapeutic agent for wound healing therapy. In vivo wound healing studies on rats for 21 days proves that ZnG/rhEGF@Chit/Polo supplements the requisite Zn2+ and rhEGF for wound healing to promote the vascular remodeling and collagen deposition, facilitate fibrogenesis, and reduce the level of interleukin 6 for wound basement repair, and thus is a good wound therapy.

pH-driven entrapment of enrofloxacin in casein-based nanoparticles for the enhancement of oral bioavailability.

Enrofloxacin (ENR), a broad-spectrum antibacterial drug, has extremely poor water solubility contributing to low bioavailability, which prevents drug formulation design and limits its wide application in livestock farming and aquaculture. Compared to conventional formulations of ENR, casein (Cas)-based drug delivery system has been reported to have significant advantages in the improvement of solubility and bioavailability of drugs. In this paper, we report the preparation process of ENR-loaded Cas nanoparticles (ENR-Cas) using magnetic agitation without any organic agent and the optimization of the formulation. Transmission electron microscopy (TEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) were all adopted to characterize the ENR-Cas. Results showed that the obtained ENR-Cas were approximately spherical with a particle size of 171.6 ± 13.8 nm with a polydispersity index of 0.322 ± 0.053. In vitro release behavior of ENR-Cas showed a sustained release profile. Additionally, in vivo study in rats displayed that the mean plasma concentration of ENR after oral administration of ENR-Cas was significantly higher than that treated with ENR suspension. The mean residence time (MRT0-24) of ENR was enhanced by Cas nanoparticles from 9.287 ± 0.524 to 11.372 ± 1.139 hr in comparison with ENR suspension. Accordingly, the area under the curve (AUC0-24) of ENR-Cas was 80.521 ± 6.624 µg·hr/ml, 3.8-fold higher than that of ENR suspension (20.850 ± 1.715 µg·hr/ml). Therefore, it can be concluded that ENR-Cas enhanced the absorption, prolonged the retention time, and improved oral bioavailability of ENR. Taken the good oral safety of Cas into consideration, ENR-Cas should be a more promising oral preparation of ENR for clinical application.

Isolation, Identification, and Anti-Inflammatory Activity of Polysaccharides of Typha angustifolia.

The present study aimed to purify, structurally characterize, and evaluate the anti-inflammatory activity of the polysaccharide extracted from Typha angustifolia. Two purified polysaccharides (PTA-1 and PTA-2) were obtained via DEAE-52 cellulose chromatography. Their structural characterizations and antioxidant activity were in vitro analyzed. To evaluate the anti-inflammatory activity of PTA-2, the levels of inflammatory cytokines, intracellular ROS production, and the inhibitory effects of the transcriptional activation of the nuclear factor kappa B (NF-κB) signaling pathway were determined. PTA-1 comprises glucose (100%) with α-(1 → 3) glycosidic bonds, and PTA-2 comprises glucose (66.7%) and rhamnose (33.3%) formed by ß-(1 → 3) glycosidic bonds. PTA-1 and PTA-2 showed strong antioxidant activity in vitro. Moreover, PTA-2 intervention (50, 100, and 200 µg/mL) suppressed the production of inflammatory cytokines, the activation of NF-κB signaling, and reactive oxygen species production significantly. The results identified PTA-2 as a natural product that could be applied in anti-inflammatory drugs.

Hitchhiking on Controlled-Release Drug Delivery Systems: Opportunities and Challenges for Cancer Vaccines.

Cancer vaccines represent among the most promising strategies in the battle against cancers. However, the clinical efficacy of current cancer vaccines is largely limited by the lack of optimized delivery systems to generate strong and persistent antitumor immune responses. Moreover, most cancer vaccines require multiple injections to boost the immune responses, leading to poor patient compliance. Controlled-release drug delivery systems are able to address these issues by presenting drugs in a controlled spatiotemporal manner, which allows co-delivery of multiple drugs, reduction of dosing frequency and avoidance of significant systemic toxicities. In this review, we outline the recent progress in cancer vaccines including subunit vaccines, genetic vaccines, dendritic cell-based vaccines, tumor cell-based vaccines and in situ vaccines. Furthermore, we highlight the efforts and challenges of controlled or sustained release drug delivery systems (e.g., microparticles, scaffolds, injectable gels, and microneedles) in ameliorating the safety, effectiveness and operability of cancer vaccines. Finally, we briefly discuss the correlations of vaccine release kinetics and the immune responses to enlighten the rational design of the next-generation platforms for cancer therapy.

The effect of web-based educational intervention on psychological status and blood glucose in newly diagnosed patients with diabetes type 2 in rural China: A protocol for randomized trial.

BACKGROUND: No studies were located which used a web-based educational intervention to improve the knowledge about newly diagnosed type 2 diabetes mellitus (T2DM). Therefore, the primary objective of the present study was to evaluate the efficacy of web-based educational intervention on psychological outcomes and glycemic control in newly diagnosed T2DM in rural China. METHODS: This work is a part of a comprehensive research project to assess and provide educational intervention that potentially improve psychological status and blood glucose among patients with T2DM. Eligibility criteria for the study includes newly diagnosed with T2DM, adult patients (age ≥30 years) regardless of gender; speak and understand Chinese languages; having no significant comorbidity; being not involved in any trial/study related to diabetes during last 3 months and able to attend regular visits. Eligible participants were divided into 2 groups according to completely randomized design: education group and control group. The outcomes included fasting blood glucose level, EQ-5D-3L questionnaire, Self-rating Anxiety Scale, and Self-rating Depression Scale. RESULTS: This protocol will provide a reliable theoretical basis for the following research. CONCLUSION: The sample came from a single health centre. Therefore, the results can not be generalized for the entire population. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6511).

Multiple-Coated PLGA Nanoparticles Loading Triptolide Attenuate Injury of a Cellular Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, which is associated with extracellular deposition of amyloid-ß proteins (Aß). It has been reported that triptolide (TP), an immunosuppressive and anti-inflammatory agent extracted from a Chinese herb Tripterygium wilfordii, shows potential neuroprotective effects pertinent to AD. However, the clinical use of TP for AD could be hampered due to its high toxicity, instability, poor water solubility, and nonspecific biodistribution after administration. In this paper, we reported a kind of multiple-coated PLGA nanoparticle with the entrapment of TP and surface coated by chitosan hydrochloride, Tween-80, PEG20000, and borneol/mentholum eutectic mixture (MC-PLGA-TP-NP) as a novel nasal brain targeting preparation for the first time. The obtained MC-PLGA-TP-NP was 147.5 ± 20.7 nm with PDI of 0.263 ± 0.075, zeta potential of 14.62 ± 2.47 mV, and the entrapment efficiency and loading efficiency of 93.14% ± 4.75% and 1.17 ± 0.08%, respectively. In comparison of TP, MC-PLGA-TP-NP showed sustained-release profile and better transcellular permeability to Caco-2 cells in vitro. In addition, our data showed that MC-PLGA-TP-NP remarkably reduced the cytotoxicity, attenuated the oxidative stress, and inhibited the increase of the intracellular Ca2+ influx in differentiated PC12 cells induced by Aß 1-42. Therefore, it can be concluded that MC-PLGA-TP-NP is a promising preparation of TP, which exerts a better neuroprotective activity in the AD cellular model.

Alginate-Based Platforms for Cancer-Targeted Drug Delivery.

As an acidic, ocean colloid polysaccharide, alginate is both a biopolymer and a polyelectrolyte that is considered to be biocompatible, nontoxic, nonimmunogenic, and biodegradable. A significant number of studies have confirmed the potential use of alginate-based platforms as effective vehicles for drug delivery for cancer-targeted treatment. In this review, the focus is on the formation of alginate-based cancer-targeted delivery systems. Specifically, some general chemical and physical properties of alginate and different types of alginate-based delivery systems are discussed, and various kinds of alginate-based carriers are introduced. Finally, recent innovative strategies to functionalize alginate-based vehicles for cancer targeting are described to highlight research towards the optimization of alginate.

Casein nanoparticles as oral delivery carriers of mequindox for the improved bioavailability.

Mequindox (Meq) is a promising broad-spectrum antibacterial agent, but the clinical application of Meq has been hampered by its low oral bioavailability. Casein (Cas) can bind to a variety of poorly water-soluble drugs to improve their water solubility through a micellar solubilization mechanism. Here, a low-cost and convenient method was introduced to prepare mequindox-loaded casein nanoparticles (Meq-Cas). Meq-Cas was characterized by several methods including differential scanning calorimetry (DSC), X-ray diffraction (XRD), and fourier transform infrared (FTIR) to illuminate the mutual effect between the drug and carriers. Meq-Cas presented nearly spherical nanoparticles with smooth surfaces and its mean particle size was lower than untreated Cas. Meq-Cas showed a nearly complete release of Meq, which displayed a biphasic drug release pattern in both phosphate-buffered solution (PBS) and simulated gastric fluid (SGF). The relative oral bioavailability of Meq-Cas was found to be about 1.20 times higher than that of the animals treated with Meq suspension (control). These results suggest that Cas is a good candidate to load in Meq for pharmaceutical purposes.

Poloxamer modified florfenicol instant microparticles for improved oral bioavailability.

Surfactants can improve the hydrophobicity of poorly water-soluble drugs and increase the stability of microparticles by reducing surface tension. This study describes that surfactant-engineered florfenicol instant microparticles (FIMs) increase bioavailability through a micellar solubilization mechanism. The FIMs were prepared by a modified emulsification method, and the optimal prescription was obtained by a combination of single factor investigation and response surface methodology. The microparticles prepared in this study reduce the polymer materials while increasing the drug content. FIM has a smaller particle size and modification of poloxamer, resulting in better solubility and higher bioavailability. The in vitro solubility of FIM is 1.43 times higher than that of the bulk drug, and the dissolution equilibrium can be achieved in 10 minutes. Compared with florfenicol, FIM showed a decrease in Tmax in the plasma concentration curve, with a peak concentration of 1.43 times and an area of 1.41 times. Considering the advantages of in vitro/in vivo performance and ease of preparation, FIMs may have great application prospects in pharmacy research.