Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

Microfluidic synthesis of zoledronic acid loaded chitosan nanoparticles used for osteogenic differentiation of mesenchymal cells.

Zoledronic acid (ZA) is known as a potent bisphosphonate in osteogenic differentiation, but at high doses, it possesses toxic effects and causes decreased proliferation and differentiation of osteoblasts. Therefore, encapsulation of ZA into nanoparticles and control of its release is expected to promote differentiation of stem cells into osteoblasts. The present work aimed to develop a simple method for synthesis of monodisperse ZA-loaded chitosan (CS) nanoparticles. In this regard, we proposed a microfluidic synthesis of nanoparticles through the ionic cross-linking of CS in the presence of ZA without a crosslinker. The main advantages of these microfluidic generated nanoparticles were narrow size distribution and fine spherical shape. Conversely, the nanoparticles that were synthesized using a bulk mixing method had an irregular shape with a broad size distribution. Real-time PCR assay as well as alizarin red staining were used to evaluate the in-vitro osteogenic potential of the nanoparticles. The results indicated that the controlled release of ZA from the microfluidic system generated uniform nanoparticles, improving the osteogenic differentiation of mesenchymal stem cells. Additionally, this microfluidic device provided the well-controlled synthesis of novel nanoparticles with a modified CS macromolecular polymer for targeted drug delivery systems.

Engineered Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as New Generations of Blood-Brain Barrier Transmitters.

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.

Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends.

Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.

Assay of bacteriorhodopsin stability on polycarbonate surface by using of FTIR-ATR: a model of disk-based bioassays.

Bacteriorhodopsin (BR) is a transmembrane protein which able to transport protons through cell membrane and thus converting solar energy to electrical energy. Up to now different strategies have been used to immobilize BR. In the present study the BR has been immobilized on polycarbonate surface with two different methods. The functional groups of polycarbonate were modified in two ways (sulfuric acid, PDAC and HNO3) and then the BR was immobilized on two different modified polycarbonate surfaces. The modified surfaces were characterized by ATR-FTIR and AFM techniques. Afterward the activity of bounded BR to two different modified polycarbonate surfaces was measured. Our results show that BR bounded to modified polycarbonate surface with HNO3 (nitrated polycarbonate) has higher activity in comparison to modified with sulfuric acid (electrostatically bounded BR). Also the activities of both types of Bounded BR after 10 days were measured. The results showed that unlike electrostatically bounded BR, bounding BR to nitrated polycarbonate keeps its activity after 10 days. In conclusion, nitrated polycarbonate surface is a suitable candidate due to immobilizing BR in order to manufacture of BioCDs.