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On-demand reconstitutable hyaluronic acid-doped azathioprine microcrystals showed enhanced therapeutic effects via colitis tissue-selective delivery of azathioprine.

The electrospinning (ES) technique in the fabrication of biomaterials-based electrospun nanofibers (ESNFs) has risen to prominence because of its accessibility, cost-effectiveness, high production rate and diverse biomedical applications. The ESNFs have unique characteristics, such as stability and mechanical performance, high permeability, porosity, high surface area to volume ratio, and ease of functionalization. The characteristics of ESNFs can be controlled by varying either process variables or biomaterial solution properties. The active pharmaceutical agents can be introduced into ESNFs by blending, surface modification, or emulsion formation. In this chapter, in the first part, we briefly discuss the fundamental aspects of the fabrication, commonly used materials, process parameters, and characterization of ESNFs. In the second part, we discuss in detail the biomedical applications of ESNFs in drug delivery, tissue engineering, and wound healings, cancer therapy, dentistry, medical filtration, biosensing and imaging of disease.

Although CD44-targeted delivery of pure drug microcrystals of azathioprine (AZA) could be a desirable approach to treat ulcerative colitis (UC), premature drug release and systemic absorption before reaching the colitis region remain a major obstacle. In this study, to overcome these limitations, we developed on-demand reconstitutable HA-doped AZA microcrystals (EFS/HA-AZAs)

Over the past decades, nanomedicine, the medical application of nanotechnology, has been extensively investigated as a promising approach in treating different inflammatory disorders and conditions. Nanomedicine provides a wide range of engineered nanomaterials, such as polymeric nanoparticles (NPs), lipid-based NPs, liposomes, silica NPs, metallic NPs, etc. Nanomaterial-based drug delivery systems exhibit multiple advantages such as the ability to pass through different physiological barriers within the body and specifically deliver drugs to the required sites without affecting healthy cells and tissues. Enormous amounts of in-vitro and in-vivo researches were previously conducted by many research groups to validate the positive contribution that nanomedicine has regarding the treatment of inflammation and its associated illnesses. The scope of this review paper is to overview the current status of using nanomaterials in the treatment of inflammatory diseases, with an emphasis on asthma, rheumatoid arthritis, inflammatory bowel disease, gout and atherosclerosis. The future prospects of using nanomaterials for inflammatory diseases were also briefly discussed.

Cyclosporine A (CsA) is a potent immunosuppressant for treating ulcerative colitis (UC). However, owing to severe systemic side effects, CsA application in UC therapy remains limited. Herein, a colon-targeted drug delivery system consisting of CsA crystals (CsAc)-loaded, Eudragit S 100 (ES)-coated alginate microparticles (CsAc-EAMPs) was established to minimize systemic side effects and enhance the therapeutic efficacy of CsA. Homogeneously-sized CsAs (3.1 ± 0.9 μm) were prepared by anti-solvent precipitation, followed by the fabrication of 47.1 ± 6.5 μm-sized CsAc-EAMPs via ionic gelation and ES coating. CsAc-EAMPs exhibited a high drug loading capacity (48 ± 5%) and a CsA encapsulation efficacy of 77 ± 9%. The in vitro drug release study revealed that CsA release from CsAc-EAMPs was suppressed under conditions simulating the stomach and small intestine, resulting in minimized systemic absorption and side effects. Following exposure to the simulated colon conditions, along with ES dissolution and disintegration of alginate microparticles, CsA was released from CsAc-EAMPs, exhibiting a sustained-release profile for up to 24 h after administration. Given the effective colonic delivery of CsA molecules, CsAc-EAMPs conferred enhanced anti-inflammatory activity in mouse model of dextran sulfate sodium (DSS)-induced colitis. These findings suggest that CsAc-EAMPs is a promising drug delivery system for treating UC.

In this study, we developed oral core-shell nanoparticles composed of curcumin nanocrystals in the core and chitosan/alginate multilayers in the shell for inflammation-targeted alleviation of ulcerative colitis (UC). The release rate of curcumin from the core-shell nanoparticles was low at a pH mimicking the stomach and small intestine, whereas it was higher at a pH mimicking the colon. Further, biodistribution studies in the gastrointestinal tract of mice showed that distribution of nanoparticles was significantly higher in the colon than that in the stomach and small intestine. Quantitative analysis of drugs in colonic tissues and confocal imaging of colons revealed preferential accumulation of nanoparticles in inflamed tissues than that in healthy tissues. In vivo anti-inflammatory studies revealed that nanoparticles exhibit enhanced efficacy in alleviating inflammation-related symptoms in a mouse colitis model. The results suggest that the core-shell nanoparticles presented here can be exploited as efficient colon-targeted drug delivery systems for UC therapy.

Nanoparticle (NP)-based drug delivery systems accumulate in the disrupted epithelium of inflamed colon tissue in ulcerative colitis. However, premature early drug release and uptake or degradation of NPs during their passage through the harsh gastric or intestinal environment compromise their therapeutic outcomes. This study aimed to develop an advanced colitis-targeted hybrid nanoparticles-in-microparticles (NPsinMPs) drug delivery system to overcome the aforementioned challenges. First, sustained drug releasing poly(lactic-co-glycolic acid) NPs were generated and further encapsulated in pH-sensitive Eudragit FS30D MPs to ensure complete drug protection in a gastric-like pH and for selective delivery of NPs to the colon. SEM and confocal microscopy for the NPsinMPs revealed successful NP encapsulation. NPsinMPs prevented drug release in an acidic gastric-like and intestinal-like pH and presented a sustained release thereafter at an ileal and colonic pH, indicating the degradation of the outer pH-sensitive MPs and release of NPs. Furthermore, in vivo imaging of gastrointestinal tract of a colitis mouse orally administered with fluorescent NPsinMPs revealed higher fluorescence intensities selectively in the colon, demonstrating the release of loaded NPs and their concomitant accumulation at the site of colon inflammation. NPsinMPs markedly mitigated experimental colitis in mice indicated by improved histopathological analysis, decreased myeloperoxidase activity, neutrophils and macrophage infiltration, and expression of proinflammatory cytokines in colonic tissues compared with NP-treated mice. The present results show the successful formulation of an NPsinMP-based drug delivery system and provide a platform to improve NP-based colon-targeted drug delivery through improved protection of encapsulated NPs and their payload in the early small intestine.

Oral colon-targeted drug delivery has gained popularity as an effective strategy for treatment of inflammatory bowel disease (IBD). In this study, we prepared colon-targeted dexamethasone microcrystals (DXMCs) coated with multilayers of chitosan oligosaccharide (CH), alginate (AG), and finally Eudragit S 100 (ES) (ES1AG4CH5-DXMCs) using a layer-by-layer (LBL) coating technique. Particle size, surface charge, in vitro drug release, and in vivo anti-inflammatory activity of ES1AG4CH5-DXMCs were evaluated. ES1AG4CH5-DXMCs had an average particle size of 2.34 ± 0.19 μm and a negative surface charge of - 48 ± 9 mV. ES1AG4CH5-DXMCs demonstrated pH-dependent dexamethasone release, avoiding initial burst drug release in acidic pH conditions of the stomach and small intestine, and providing subsequent sustained drug release in the colonic pH. Importantly, ES1AG4CH5-DXMCs exhibited a significant therapeutic activity in a mouse model of colitis compared to other DXMCs. Overall, the LBL-coated DXMCs presented here could be a promising colon-targeted therapy for IBD.

Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery. Targeting ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle surface. However, poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as PLGA. In this study, we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly (ethylene-alt-maleic acid) (PEMA). Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching method. The presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential measurements. Using the improved film-stretching method, the amount of protein conjugated to the surface of nanorods was increased three-fold. Transferrin-conjugated, nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified counterparts. Therefore, the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro- and nanoparticles with high capacity of surface modifications for enhanced targeted delivery., Graphical abstract Image, graphical abstract

Background Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer. Methods CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. Results PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. Conclusion Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

Adhesion of nanoparticles (NPs) to the bacterial cell wall by modifying their physicochemical properties can improve the antibacterial activity of antibiotic. In this study, we prepared positively charged clindamycin-loaded poly (lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI) nanoparticles (Cly/PPNPs) and negatively charged clindamycin-loaded PLGA NPs (Cly/PNPs) and investigated the effect of NP adhesion to bacteria on the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The Cly/PPNPs and Cly/PNPs were characterized according to particle size, polydispersity index, surface charge, and drug loading. Both Cly/PPNPs and Cly/PNPs exhibited sustained drug release over 2 days. The Cly/PPNPs bind to the MRSA surface, thereby enhancing bactericidal efficacy against MRSA compared with the Cly/PNPs. Furthermore, compared with other groups, Cly/PPNPs significantly accelerated the healing and re-epithelialization of wounds in a mouse model of a MRSA-infected wounds. We also found that both NPs are harmless to healthy fibroblast cells. Therefore, our results suggest that the Cly/PPNPs developed in this study improve the efficacy of clindamycin for the treatment of MRSA-infected wounds.

Objective: To determine the current supply and demand for Amoxicillin 500 mg capsules at the pharmaceutical market level based on readily available and comparative data methods.Study Design: Cross-sectional.Place and Duration of Study: The study was carried out at hundred pharmacies spread throughout the three cities of Khartoum State (Khartoum, Omdurman, and Khartoum-North) from April 4, 2018 to June 17, 2018.Materials and Methods: A market survey was conducted by visiting 100 pharmacies and basic questions were posed directly to the pharmacist about the annual sale of Amoxicillin 500 mg capsules through a questionnaire. The data was analyzed using the consumption process, and the projected actual demand for amoxicillin 500 mg capsules up to the year 2027 in Sudanese markets was estimated.Results: The analyzed data showed a difference of about 756 million capsules between the current supply and real demand of 500 mg capsules of amoxicillin up to 2027. Moreover, the findings showed that there are substantial variations in annual sales of amoxicillin 500 mg capsules among the three cities where the survey was performed.Conclusion: The results of this study can be used as a guide for estimating the actual demands for Amoxicillin 500 mg capsules in the Sudanese pharmaceutical market for the future.

In this study, we developed pH-triggered surface charge-reversal lipid nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the drug to inflamed colon segments for the treatment of ulcerative colitis. Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and Eudragit® S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge-reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic conditions mimicking the stomach and early small intestine environments and showed a sustained release in the colon. The surface charge of ES-PEI-LNPs switched from negative to positive under colonic conditions owing to pH-triggered removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs could be a promising drug carrier for ulcerative colitis therapy and other colon-targeted treatments.

Objective: Tribes in Nubia Mountains regions of Sudan used Monechma ciliatum seeds for common cold and other chest allergic conditions as a traditional medicine. The aim of this paper is to validate this traditional practice scientifically. Materials and Methods: Monechma ciliatum seeds were screened for major phytochemical groups using standard methods. Different extracts were bioassayed in- vitro for their bioactivity to inhibit the growth of pathogenic bacteria and fungi. Results: Phytochemical screening results showed the presence of flavonoids, tannins, triterpens, and anthraquinones. Staphylococcus aureus was found to be sensitive to both water extract with zones of inhibition 22 – 26 mm at concentrations of 50 and 100mg/ml and ethanol extract 17 mm at concentration of 100 mg/ml. The growth of Klebsiella pneumoniae was inhibited by ethanol extract with zones of inhibition equal to 16, 26, and 33 mm at concentrations of 50, 100, and 150 mg/ml, respectively. Pseudomonas aeruginosa was insensitive to all extracts used. Similarly, all used fungi were found to be insensitive to extracts used. The minimum inhibitory concentrations of the extracts against microorganisms were ranged from 12.5 to 25 mg/ml. Conclusion: The findings of the current study support the traditional uses of the plant's seed in the therapy of respiratory tract infections caused by Staphylococcus aureus and Klebsiella pneumoniae.