PREPARATION OF CHITOSAN-TPP NANOPARTICLES: THE INFLUENCE OF CHITOSAN POLYMERIC PROPERTIES AND FORMULATION VARIABLES

Objective: The aim of this work was to prepare chitosan nanoparticles (CS NPs) using sodium tripolyphosphate (TPP) as crosslinker and to study the effect of chitosan polymeric properties and experimental conditions on the properties and stability of NPs.Methods: CS NPs were prepared by ionic gelation method, using TPP as a crosslinker. The particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the morphologies of the NPs were studied. CS NPs prepared by varying the concentration of TPP, Chitosan molecular weight and its degree of deacetylation, the stirring speed, the rate of TPP addition and the freeze-drying method to study the effect of these variables on the NPs. The stability of the CS NPs was evaluated by storing aqueous suspensions of NPs and comparing the PS, PDI and ZP at the beginning and the end of the experiment.Results: This study shows that the PS, ZP and dispersity of the NPs depend on the chitosan polymeric properties and experimental conditions. The NPs sizes range between 145.73 and 724.23 nm. They all carried positive charges ranging between+4.32 and+43.67 mV. Most of the NPs have the same sizes after freeze-drying, but showed higher monodispersity and ZP, indicating higher stability. After twenty days of studying the stability, the NPs that had low ZP showed a large increment in size in comparison to the highly charged NPs.Conclusion: In conclusion, the polymeric properties and formulation variables in the ionic gelation method have a great influence on the CS NPs formed

Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma

© 2019 Elsevier B.V. The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma

Synthesis and characterization of photocatalytic polyurethane and poly(methyl methacrylate) microcapsules for the controlled release of methotrexate

The aim of this work is to prepare ultraviolet (UV) triggered controlled release of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl methacrylate) (PMMA) microcapsules were studied with/without chemical functionalization using photocatalytic TiO2 nanoparticles (NPs) on their surface. Once TiO2 nanoparticles are illuminated with UV light (λ = 370 nm), they initiate the rupture of the polymeric bonds of the microcapsule and subsequently initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh), in the present work. The size, polydispersity, charge, and yield of all MCs were measured, being the methotrexate drug release for all systems determined and compared with and without functionalization with TiO2 NPs, under dark, visible light and UV illumination in vitro. Finally, the Rh release was characterized using fluorescence microscopy. The TiO2 NPs size is around 10 nm, as determined by X-ray diffraction experiments. The PU MCs average size is around 60 µm, its electric charge +3.11 mV and yield around 85%. As for the PMMA MCs, the average size is around 280 µm, its electric charge −7.2 mV and yield around 25% and 30% for both MTX and Rh, respectively. In general, adding TiO2 NPs or the encapsulated products to the MCs does not affect the size but functionalization with TiO2 NPs lowers the electric charge. Microcapsules functionalized with TiO2 nanoparticles and irradiated with UV light presented the highest release of MTX and Rh. All other samples showed lower drug release levels when studied under the same conditions.The authors thank the deanship of research at Jordan University of Science and Technology (JUST) for their generous fund (Proposal Number: 161/2016). Juliana Marques kindly acknowledges the funding for her Ph.D grant from the Portuguese institution Fundação para a Ciência e Tecnologia – FCT [SFRH/BD/112868/2015]

Photolytic Controlled Release Formulation of Methotrexate Loaded in Chitosan/TiO2 Nanoparticles for Breast Cancer

A new system composed of chitosan nanoparticles loaded with methotrexate (MTX-CS-NPs) and functionalized with photocatalytic TiO2 nanoparticles (TiO2-NPs) was prepared. This system is expected to initiate polymeric rupture of MTX-CS-NPs and subsequently release MTX, upon illumination with UV light. MTX-CS-NPs were prepared and characterized in terms of particle size, charge, polydispersity and drug release before and after coating with TiO2-NPs. The release of MTX in vitro was studied in dark, light and UV light. Finally, coated and uncoated MTX-CS-NPs were studied in vitro using MCF-7 cell line. The functionalized NPs were larger in size, more polydisperse and carried higher positive charges compared to the unfunctionalized NPs. The entrapment efficacy was high reaching 75% and was not affected by coating with MTX-CS-NPs. Further, less than 5% of methotrexate was released after 80 h from uncoated NPs and the release was not enhanced by UV illumination of the particles. In contrast, the release from functionalized NPs was enhanced, reaching 40% after 80 h, as the particles were stroked with UV light and as the amount of TiO2-NPs used in coating increased. Finally, coating the MTX-CS-NPs with TiO2-NPs significantly enhanced their cytotoxicity on MCF-7 cells. The coated MTX-CS-NPs recorded low cell viabilities compared to the other formulations. In conclusion, the drug release of MTX-CS-NPs could be triggered and controlled remotely by coating with TiO2-NPs, which maybe more effective in cancer treatment

Green Synthesis of Silver Nanoparticles Using Bellevalia Flexuosa Leaves Extract

Silver nanoparticles (AgNPs) have broad biocidal activities, and are widely employed as an active ingredient in antiseptic, anti-viral, and anti-inflammatory preparations. Green-synthesizing AgNPs would be a rapid, cheap, and environmentally friendly method of synthesis. The methanolic extract of the leaves of Bellevalia flexuosa Boiss. (Asparagaceae) was used for the green synthesis of the AgNPs. The effects of the pH and the concentration of silver nitrate (AgNO3) on the synthesis of the AgNPs were investigated. The AgNPs produced above pH 10, and 1 mM of AgNO3 resulted in lower hydrodynamic diameters. Ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction proved the formation of the AgNPs, with a face-centered, cubed geometry. Scanning electron microscopy images showed colloidal and well-dispersed nanoparticles. In addition, the antibacterial activities of the prepared AgNPs were assessed by optical densities (ODs) against Gram-positive bacteria (Enterococcus faecalis and Staphylococcus epidermidis) and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica). The broths of Gram-negative and Gram-positive bacteria that contained AgNPs, showed lower OD values compared to the controls. In conclusion, AgNPs were prepared using B. flexuosa methanolic extract, and showed antibacterial activity against the tested bacterial strains

Low Molecular Weight Chitosan-Coated PLGA Nanoparticles for Pulmonary Delivery of Tobramycin for Cystic Fibrosis

(1) Background: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Tobramycin were prepared using a solvent-evaporation method. (2) Methods: The NPs were coated with low molecular weight chitosan (LMWC) to enhance the mucoadhesiveness of PLGA-NPs. The following w/w ratios of tobramycin to LMWC were prepared: control (0:0.50), F0 (1:0.25), F0.5 (1:0.5), and F1 (1:1). (3) Results: The results showed that the size of the particles increased from 220.7 nm to 575.77 nm as the concentration of LMWC used in the formulation increased. The surface charge was also affected by the amount of LMWC, where uncoated-PLGA nanoparticles had negative charges (−2.8 mV), while coated-PLGA NPs had positive charges (+33.47 to +50.13 mV). SEM confirmed the size and the spherical homogeneous morphology of the NPs. Coating the NPs with LMWC enhanced the mucoadhesive properties of the NPs and sustained the tobramycin release over two days. Finally, all NPs had antimicrobial activity that increased as the amount of LMWC increased. (4) Conclusion: In conclusion, the formulation of mucoadhesive, controlled-release, tobramycin-LMWC-PLGA nanoparticles for the treatment of P. aeruginosa in cystic fibrosis patients is possible, and their properties could be controlled by controlling the concentration of LMWC

Polymeric Nanoparticles for Inhaled Vaccines

Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose