Enhanced oral bioavailability through nanotechnology in Saudi Arabia: A meta-analysis

Oral administration represents the most suitable mean among different means of administering drugs because it ensures high compliance by patients. Nevertheless, the lacking aqueoussolubility, as well as, inadequate metabolic/enzymatic stability of medicines are leading obstacles to successful drug administration by oral route. Among different systems, drug administration systems based on nanotechnology have the potential to surmount the problems associated with oral drug administration. Drug delivery systems based on nanotechnology offer an alternative to deliver antihypertensive agents with enhanced therapeutic effect and bioavailability. In this study, meta-analysis was utilized in combining data relating to oral bioavailability (area under plasma concentration time curve, AUC) enhancement through nanotechnology from multiple studies. Twenty-one studies of the total 37articles included in this study were from the kingdom of Saudi Arabia and were included in a specific meta-analysis. From the analysis conducted, the overall enhancement power of the nanotechnology based formulations on drug bioavailability was found to be 7.94% (95 %CI [5.809, 10.064]). Haven utilized comprehensive and recent data of the confirmed the enhancement of bioavailability using nanotechnology which for this study was grouped into five: solid lipid nanoparticles; polymer based nanoparticles; SNEEDS/Nanoemulsion; liposomes/proliposomes and; nanostructured lipid carriers. Furthermore, the meta-analysis, provided evidence of insignificant differences between APG Bio-SNEDDS and its free drug suspension (Apeginin, APG), though with relative bioavailabiilty of 1.91. Notwithstanding most of the treatment showed a substantial relative bioavailability.     

Size,surface charge and flexibility of vinegar-baked Radix Bupleuri polysaccharide affecting the immune response

Remarkably, nanomaterials can interact with the cells of immune system and either enhance or inhibit its function in many ways. Unfortunately, such valuable information has been overlooked in studies of polysaccharide immune activity. This study isolated a nano-polysaccharide from vinegar-baked Radix Bupleuri by membrane separation system, DEAE-52 and Sephadex-G200. The physicochemical characterization and immunoregulatory activity were studied through DLS, Congo red, Scanning Electron Microscope, UV–Vis, HPGPC, FT-IR, Methylation, NMR, MTT, neutral red and enzyme linked immunosorbent assay. Results showed that VBCP2.5 was an acidic polysaccharide with a molecular weight of 674 kDa. Its monosaccharides composed of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose at a molar ratio of 1.72: 9.59: 57.63: 5.37: 6.71: 18.99. VBCP2.5 possessed micelle forming ability at 52.574 µg/mL and flexible chain conformation, as well as with a small size distribution ～ 84.99 nm and positive charge in stimulated blood fluid and different from that in deionized water. The microtopography was characterized by irregular lamellar, dendritic, cylindrical or spherical aggregates, with folds and cracks on the surface. Structure analyses showed that VBCP2.5 characterized by high proportion of 1,4 linked-α-D-GalpA and a small fraction of RG-I, some other glycosidic linkages included 1,5 linked-α-L-Araf, 1,3,5 linked-α-L-Araf, 1,3,4 linked-Galp, 1,4,6 linked-Manp, t-α-L-Araf, t-β-D-Glcp and t-α-D-Galp were also comprised. VBCP2.5 exhibited immunomodulatory potential which included the promotion of phagocytosis, the release of NO and the secretion of TNF-α and IL-6 of RAW264.7 cells. The possible activation of macrophages by VBCP2.5 may be mediated through endocytosis pathway. Small size, positive charge, shape and flexible conformation may accelerate this process. The information gathered here could lead to new platform for comprehensive understand included primary structure, properties of nanoscale, and correlation with immunoregulation of polysaccharides.     

Investigation of the effect of nozzle shape on supersonic/hypersonic impactors designed for size discrimination of nanoparticles

In this study the flow field and the nanoparticle collection efficiency of supersonic/hypersonic impactors with different nozzle shapes were studied using a computational modeling approach. The aim of this study was to develop a nozzle design for supersonic/hypersonic impactors with the smallest possible cut-off size d₅₀ and rather sharp collection efficiency curves. The simulation results show that the changes in the angle and width of a converging nozzle do not alter the cut-off size of the impactor; however, using a conical Laval nozzle with an L/D_n ratio less than or equal to 2 reduced d₅₀. The effect of using a cap as a focuser in the nozzle of a supersonic/hypersonic impactor was also investigated. The results show that adding a cap in front of the nozzle had a noticeable effect on decreasing the cut-off size of the impactor. Both flat disks and conical caps were examined, and it was observed that the nozzle with the conical cap had a lower cut-off size.     

Emission of molecular fragments synthesized in hypervelocity nanoparticle impacts

We report on experiments with Au_n nanoparticles (100 ≤ n ≤ 400) at velocities of 10–60 km/s. They are implanted virtually intact via hydrodynamic penetration. The products of the extreme pressure transient are observed by mass analyzing the ionized ejecta. Targets of labeled molecules (¹³C-, ¹⁵N-glycine) reveal fragmentation–recombination processes, producing CN⁻ and OCN⁻ with high efficiency (45%). This value is over two orders of magnitude larger than that obtained with atomic and small cluster projectiles. The experiments could simulate collisions of nanosized dust particles in interstellar space.     

Underpotential surface reduction of mesoporous CeO<Subscript>2</Subscript> nanoparticle films

The formation of variable-thickness CeO₂ nanoparticle mesoporous films from a colloidal nanoparticle solution (approximately 1–3-nm-diameter CeO₂) is demonstrated using a layer-by-layer deposition process with small organic binder molecules such as cyclohexanehexacarboxylate and phytate. Film growth is characterised by scanning and transmission electron microscopies, X-ray scattering and quartz crystal microbalance techniques. The surface electrochemistry of CeO₂ films before and after calcination at 500 °C in air is investigated. A well-defined Ce(IV/III) redox process confined to the oxide surface is observed. Beyond a threshold potential, a new phosphate phase, presumably CePO₄, is formed during electrochemical reduction of CeO₂ in aqueous phosphate buffer solution. The voltammetric signal is sensitive to (1) thermal pre-treatment, (2) film thickness, (3) phosphate concentration and (4) pH. The reversible ‘underpotential reduction’ of CeO₂ is demonstrated at potentials positive of the threshold. A transition occurs from the reversible ‘underpotential region’ in which no phosphate phase is formed to the irreversible ‘overpotential region’ in which the formation of the cerium(III) phosphate phase is observed. The experimental results are rationalised based on surface reactivity and nucleation effects.     

NOVEL pH-SENSITIVE DRUG DELIVERY SYSTEM BASED ON NATURAL POLYSACCHARIDE FOR DOXORUBICIN RELEASE

A novel pH-sensitive nanoparticle drug delivery system (DDS) derived fl'om natural polysaccharide pullulan for doxorubicin (DOX) release was prepared.Pullulan was functionalized by successive carboxymethylization and amidation to introduce hydrazide groups.DOX was then grafted onto pullulan backbone through the pH-sensitive hydrazone bond to form a pullulan/DOX conjugate.This conjugate self-assembled to form nano-sized particles in aqueous solution as a result of the hydrophobic interaction of the DOX.Tr...     

Activatable NIR-II Photothermal Lipid Nanoparticles for Improved Messenger RNA Delivery

Endosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near-infrared (NIR-II) lipid nanoparticles (LNPs) containing pH activatable NIR-II dye conjugated lipid (Cy-lipid) for potentiating mRNA delivery efficiency via a s timulus-responsive p hotothermal-promoted e ndosomal e scape d elivery (SPEED) strategy. In acidic endosomal microenvironment, Cy-lipid is protonated and turns on NIR-II absorption for light-to-heat transduction mediated by 1064 nm laser irradiation. Then, the heat-promoted LNPs morphology change triggers rapid escape of NIR-II LNPs from the endosome, allowing about 3-fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR-II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy.     

Effect of Incorporation of Silver on the Electrical Properties of Sol-Gel-Derived Titania Film

Metallic Ag nanoparticles-incorporating titania films were prepared using the sol-gel method. X-ray diffraction (XRD) patterns, UV/Vis optical spectra and transmission electron microscopy (TEM) images were recorded to characterize the Ag/titania composite films. Electrometer was used to estimate the resistance of Ag/titania composite film to understand the effect of the incorporation of metallic Ag nanoparticles on the electrical properties of titania film. The results showed that metallic Ag nanoparticles distributed randomly in titania film and most metallic Ag particles size was in the range of 5–15 nm. The agglomeration of a small quantity of metallic Ag particles occurred and when the amount of Ag species was increased the agglomeration was enhanced. The resistance of Ag/titania composite films decreased greatly compared with pure titania film.     

An In Situ Investigation of the Protein Corona Formation Kinetics of Single Nanomedicine Carriers by Self-Regulated Electrochemiluminescence Microscopy

Protein coronas are present extensively at the bio-nano interface due to the natural adsorption of proteins onto nanomaterials in biological fluids. Aside from the robust property of nanoparticles, the dynamics of the protein corona shell largely define their chemical identity by altering interface properties. However, the soft coronas are normally complex and rapidly changing. To real-time monitor the entire formation, we report here a self-regulated electrochemiluminescence (ECL) microscopy based on the interaction of the Ru(bpy)₃³⁺ with the nanoparticle surface. Thus, the heterogeneity of the protein corona is in situ observed in single nanoparticle “cores” before and after loading drugs in nanomedicine carriers. The label-free, optical stable and dynamic ECL microscopy minimize misinterpretations caused by the variation of nanoparticle size and polydispersity. Accordingly, the synergetic actions of proteins and nanoparticles properties are uncovered by chemically engineered protein corona. After comparing the protein corona formation kinetics in different complex systems and different nanomedicine carriers, the universality and accuracy of this technique were well demonstrated via the protein corona formation kinetics curves regulated by competitive adsorption of Ru(bpy)₃³⁺ and multiple proteins on surface of various carriers. The work is of great significance for studying bio-nano interface in drug delivery and targeted cancer treatment.     

Tandem Guest-Host-Receptor Recognitions Precisely Guide Ciprofloxacin to Eliminate Intracellular Staphylococcus aureus

Staphylococcus aureus (S. aureus) is able to hide within host cells to escape immune clearance and antibiotic action, causing life-threatening infections. To boost the therapeutic efficacy of antibiotics, new intracellular delivery approaches are urgently needed. Herein, by rational design of an adamantane (Ada)-containing antibiotic-peptide precursor Ada-Gly-Tyr-Val-Ala-Asp-Cys(StBu)-Lys(Ciprofloxacin)-CBT ( Cip-CBT-Ada ), we propose a strategy of tandem guest-host-receptor recognitions to precisely guide ciprofloxacin to eliminate intracellular S. aureus. Via guest-host recognition, Cip-CBT-Ada is decorated with a β-cyclodextrin-heptamannoside ( CD-M ) derivative to yield Cip-CBT-Ada/CD-M , which is able to target mannose receptor-overexpressing macrophages via multivalent ligand-receptor recognition. After uptake, Cip-CBT-Ada/CD-M undergoes caspase-1 (an overexpressed enzyme during S. aureus infection)-initiated CBT-Cys click reaction to self-assemble into ciprofloxacin nanoparticle Nano-Cip . In vitro and in vivo experiments demonstrate that, compared with ciprofloxacin or Cip-CBT-Ada , Cip-CBT-Ada/CD-M shows superior intracellular bacteria elimination and inflammation alleviation efficiency in S. aureus-infected RAW264.7 cells and mouse infection models, respectively. This work provides a supramolecular platform of tandem guest-host-receptor recognitions to precisely guide antibiotics to eliminate intracellular S. aureus infection efficiently.