scholarly journals Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 282
Author(s):  
Zahra Davoudi ◽  
Nathan Peroutka-Bigus ◽  
Bryan Bellaire ◽  
Albert Jergens ◽  
Michael Wannemuehler ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Positive Charge ◽  
Ex Vivo ◽  
Plga Nanoparticles ◽  
Serosal Side ◽  
Coated Nanoparticles ◽  
Charged Nanoparticles ◽  
The Impact ◽  
Positively Charged

Intestinal organoids can be used as an ex vivo epithelial model to study different drug delivery effects on epithelial cells’ luminal surface. In this study, the impact of surface charge on the delivery of 5-ASA loaded PLGA nanoparticles into the lumen of organoids was investigated. Alginate and chitosan were used to coat the nanoparticles and provide negative and positive charges on the particles, respectively. The organoid growth and viability were not affected by the presence of either alginate- or chitosan-coated nanoparticles. It was shown that nanoparticles could be transported from the serosal side of the organoids to the lumen as the dye gradually accumulated in the lumen by day 2–3 after adding the nanoparticles to the Matrigel. By day 5, the dye was eliminated from the lumen of the organoids. It was concluded that the positively charged nanoparticles were more readily transported across the epithelium into the lumen. It may be attributed to the affinity of epithelial cells to the positive charge. Thus, the organoid can be utilized as an appropriate model to mimic the functions of the intestinal epithelium and can be used as a model to evaluate the benefits of nanoparticle-based drug delivery.

scholarly journals Quaternary Ammonium Chitosans: The Importance of the Positive Fixed Charge of the Drug Delivery Systems

2020 ◽  
Vol 21 (18) ◽  
pp. 6617 ◽  
Author(s):  
Angela Fabiano ◽  
Denise Beconcini ◽  
Chiara Migone ◽  
Anna Maria Piras ◽  
Ylenia Zambito
Keyword(s):  
Drug Delivery ◽  
Quaternary Ammonium ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Fixed Charge ◽  
Innovative Drug ◽  
Natural Polysaccharide ◽  
The Impact

As a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption.

scholarly journals DEVELOPMENT OF MUCOADHESIVE CHITOSAN-BASED DRUG DELIVERY SYSTEM

2018 ◽  
Vol XXIII ◽  
pp. 103-113
Author(s):  
Mariya Konovalova ◽  
Balzhima Shagdarova ◽  
Anastasia Zubareva ◽  
Alexander Generalov ◽  
Maria Grechikhina ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Small Intestine ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Mucous Membranes ◽  
Colon Cell ◽  
Reactive Groups ◽  
Low Toxicity ◽  
Positively Charged

Chitosan is a highly versatile biopolymer characterised by low toxicity, biocompatibility, and slow but complete biodegradation in the human body, possessing multiple reactive groups. One of the most well-known properties of positively charged chitosan derivatives is their ability to bind mucous membranes. The aim of this work was the analysis of mucoadhesion of unmodified 20 kDa chitosan and its hydrophobic (HC) and hydrophobic quaternised (QHC) derivatives in vitro and ex vivo. Unmodified chitosan formed large aggregates in vitro in keratinocyte and colon cell cultures and ex vivo in murine small intestine and muscle explants. At the same time, HC and especially QHC bound cells in vitro and ex vivo in a fine dotted manner, as evidenced by confocal microscopy. Such a pattern of hydrophobic derivatives distribution provides the possibility to develop mucoadhesive drug delivery systems with increased local drug release and improved chitosan biodegradation.

scholarly journals Pharmacokinetics of Pullulan–Dexamethasone Conjugates in Retinal Drug Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 12
Author(s):  
Eva Kicková ◽  
Amir Sadeghi ◽  
Jooseppi Puranen ◽  
Shirin Tavakoli ◽  
Merve Sen ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Large Fraction ◽  
Delivery Systems ◽  
Intravitreal Injections ◽  
Aqueous Humor Outflow ◽  
Charged Nanoparticles ◽  
Average Size

The treatment of retinal diseases by intravitreal injections requires frequent administration unless drug delivery systems with long retention and controlled release are used. In this work, we focused on pullulan (≈67 kDa) conjugates of dexamethasone as therapeutic systems for intravitreal administration. The pullulan–dexamethasone conjugates self-assemble into negatively charged nanoparticles (average size 326 ± 29 nm). Intravitreal injections of pullulan and pullulan–dexamethasone were safe in mouse, rat and rabbit eyes. Fluorescently labeled pullulan particles showed prolonged retention in the vitreous and they were almost completely eliminated via aqueous humor outflow. Pullulan conjugates also distributed to the retina via Müller glial cells when tested in ex vivo retina explants and in vivo. Pharmacokinetic simulations showed that pullulan–dexamethasone conjugates may release free and active dexamethasone in the vitreous humor for over 16 days, even though a large fraction of dexamethasone may be eliminated from the eye as bound pullulan–dexamethasone. We conclude that pullulan based drug conjugates are promising intravitreal drug delivery systems as they may reduce injection frequency and deliver drugs into the retinal cells.

scholarly journals A55 INVESTIGATING THE ROLE OF ENDOGENOUS INTERLEUKIN-10 IN INTESTINAL EPITHELIAL CELLS AND HOMEOSTASIS

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 12-13
Author(s):  
H D Nguyen ◽  
A Stadnyk
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Ex Vivo ◽  
Gene Knockout ◽  
Immunofluorescent Staining ◽  
Absorptive Cell ◽  
Small Intestinal Epithelium ◽  
Basolateral Side ◽  
Small Intestinal ◽  
The Impact

Abstract Background IL-10 is appreciated for its potent anti-inflammatory effects on leukocytes in mucosal immunity. However, far less attention has been paid to the impact of IL-10 on epithelial cells, which make up the crucial barrier interface between the host mucosa and the external environment. Furthermore, most studies examine the effects of exogenous IL-10, disregarding the possible presence and function of autocrine or paracrine IL-10 in the epithelium. Aims Using ex vivo organoids we aimed to examine the small intestinal epithelium for IL-10 and dissect any role for endogenously produced cytokine. Methods We growed small intestinal organoids (enteroids) from crypts isolated from C57BL/6 mice (WT) and IL-10-gene knockout mice (IL-10KO). Cellular markers were characterized through qpCR, while IL-10 and IL-10 receptor localization was characterized though immunofluorescence. Results We discovered that cells in WT enteroids expressed IL-10 and IL-10R1 constitutively throughout development. Immunofluorescent staining revealed that IL-10 localizes to Paneth cells and appears to be secreted apically. Having established that IL-10 is secreted in enteroids, we compared enteroids from IL-10KO versus WT mice. IL-10KO enteroids developed to morphologically resemble WT enteroids; however, we detected an imbalance with lower secretory cell markers over absorptive cell types in the IL-10KO enteroids, measured as less mRNA for lysozyme, cryptdins and mucin-2. Addition of IL-10 to IL-10KO enteroids did not correct these defects, but did ameliorate the lineage balance by reducing absorptive cell lineage markers (sucrose isomaltase). IL-10R1 was localized on both apical and basolateral side of cell in enteroids. We suspect that epithelial-derived IL-10 likely acts on apical IL-10R, which may conduct a different response from basolateral receptor stimulation. Conclusions In conclusion, IL-10 is present in the small intestinal epithelium; more remains to be determined regarding the role this cytokine plays in gut development and homeostasis. Funding Agencies NSERC

scholarly journals Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

2015 ◽  
Vol 6 ◽  
pp. 300-312 ◽  
Author(s):  
Lisa Landgraf ◽  
Ines Müller ◽  
Peter Ernst ◽  
Miriam Schäfer ◽  
Christina Rosman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Research Field ◽  
Size Dependent ◽  
General Rules ◽  
Charged Nanoparticles ◽  
20 Nm ◽  
The Impact ◽  
Insight Into ◽  
Positively Charged

In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.

scholarly journals House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1151
Author(s):  
Malik Aydin ◽  
Ella A. Naumova ◽  
Friedrich Paulsen ◽  
Wenli Zhang ◽  
Felix Gopon ◽  
...  
Keyword(s):  
Cell Culture ◽  
Epithelial Cells ◽  
House Dust ◽  
House Dust Mite ◽  
Fluorescent Protein ◽  
Ex Vivo ◽  
Study Cohort ◽  
Nasal Epithelial Cells ◽  
Dust Mite ◽  
The Impact

Adenovirus (AdV) infections in the respiratory tract may cause asthma exacerbation and allergic predisposition, and the house dust mite (HDM) may aggravate virus-induced asthma exacerbations. However, the underlying mechanisms of whether and how AdV affects asthmatic patients remains unclear. To address this question, we investigated nasal epithelial cells (NAEPCs) derived from a pediatric exacerbation study cohort for experimental analyses. We analyzed twenty-one different green-fluorescent protein- and luciferase-tagged AdV types in submerged 2D and organotypic 3D cell culture models. Transduction experiments revealed robust transduction of AdV type 5 (AdV5) in NAEPCs, which was associated with an increased uptake of AdV5 in the presence of HDM. In healthy and asthmatic NAEPCs exposed to HDM before infection, we observed a time- and dose-dependent increase of AdV5 uptake associated with upregulation of entry receptors for AdV5. Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma.

scholarly journals Drug Release Studies of SC-514 PLGA Nanoparticles

2021 ◽  
pp. 1-21
Author(s):  
Famuyiwa Toluleke Oloruntobi ◽  
Bowers Zoey ◽  
Bentley Austin ◽  
Caraballo Davian ◽  
Subtil Paulynice ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Drug Release ◽  
Tumor Growth ◽  
Drug Delivery Systems ◽  
Plga Nanoparticles ◽  
Delivery Systems ◽  
New Methods ◽  
Coated Nanoparticles

A major problem associated with prostate cancer treatment is the development of drug resistance. The development of drug resistance often leads to prostate cancer metastasis and prostate cancer-targeted drug delivery systems can be utilized to address this problem. Traditional drug delivery systems have many challenges, including the inability to control the drug release rate, target site inaccuracy, susceptibility to the microenvironment, poor drug solubility, and cytotoxicity of chemotherapeutics to non-malignant cells. As a result, there is an urgent need to formulate and functionalize a drug delivery system that better controls drug release. This study was designed to quantify the release of SC-514 from SC-514 Polylactic-Co-Glycolic Acid (PLGA) nanoparticles and conjugate SC-514-PLGA coated nanoparticles with the NF- κβ antibody, as well as fats. This study further explored new methods to quantify the release of SC-514 drug from the SC-514-PLGA coated nanoparticles after utilizing Liquid Chromatography–Mass Spectrometry (LC-MS) as the standard method to quantify SC-514 drug released. After quantification was completed, cell viability studies indicated that the ligand conjugated nanoparticles demonstrated a considerable ability to reduce tumor growth and SC-514 drug toxicity in the PC-3 cell line. The prepared drug delivery systems also possessed a significantly lower toxicity (P<0.05), bettered controlled-release behaviors in prostate cancer, and increased the solubility of SC-514 in comparison to free SC-514. SC-514 released from SC-514-PLGA, SC-514-PLGA-NF- κβAb, and SC-514-PLGA-Fat nanoparticles, significantly inhibited tumor growth when compared to that of free SC-514. The anti-cancer therapeutic effects of SC-514 were improved through the encapsulation of SC-514 with a PLGA polymer. The functionalized SC-514-PLGA nanoparticles can further control burst release. The new methods utilized in this study for quantifying drug release, may prove to be as effective as the current standard methods, such as LC/MS.

scholarly journals Dye-doped silica nanoparticles: synthesis, surface chemistry and bioapplications

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vladimir Gubala ◽  
Giorgia Giovannini ◽  
Filip Kunc ◽  
Marco P. Monopoli ◽  
Colin J. Moore
Keyword(s):  
Drug Delivery ◽  
Silica Nanoparticles ◽  
Fluorescent Dyes ◽  
Nanoparticle Synthesis ◽  
Protein Corona ◽  
Synthesis Methods ◽  
Main Body ◽  
Coated Nanoparticles ◽  
The Impact ◽  
Doped Nanomaterials

Abstract Background Fluorescent silica nanoparticles have been extensively utilised in a broad range of biological applications and are facilitated by their predictable, well-understood, flexible chemistry and apparent biocompatibility. The ability to couple various siloxane precursors with fluorescent dyes and to be subsequently incorporated into silica nanoparticles has made it possible to engineer these fluorophores-doped nanomaterials to specific optical requirements in biological experimentation. Consequently, this class of nanomaterial has been used in applications across immunodiagnostics, drug delivery and human-trial bioimaging in cancer research. Main body This review summarises the state-of-the-art of the use of dye-doped silica nanoparticles in bioapplications and firstly accounts for the common nanoparticle synthesis methods, surface modification approaches and different bioconjugation strategies employed to generate biomolecule-coated nanoparticles. The use of dye-doped silica nanoparticles in immunoassays/biosensing, bioimaging and drug delivery is then provided and possible future directions in the field are highlighted. Other non-cancer-related applications involving silica nanoparticles are also briefly discussed. Importantly, the impact of how the protein corona has changed our understanding of NP interactions with biological systems is described, as well as demonstrations of its capacity to be favourably manipulated. Conclusions Dye-doped silica nanoparticles have found success in the immunodiagnostics domain and have also shown promise as bioimaging agents in human clinical trials. Their use in cancer delivery has been restricted to murine models, as has been the case for the vast majority of nanomaterials intended for cancer therapy. This is hampered by the need for more human-like disease models and the lack of standardisation towards assessing nanoparticle toxicity. However, developments in the manipulation of the protein corona have improved the understanding of fundamental bio–nano interactions, and will undoubtedly assist in the translation of silica nanoparticles for disease treatment to the clinic.

scholarly journals Enhanced intraperitoneal delivery of charged, aerosolized curcumin nanoparticles by electrostatic precipitation

Nanomedicine ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. 109-120
Author(s):  
Arianna Castagna ◽  
Alexandra J Zander ◽  
Iaroslaw Sautkin ◽  
Marc Schneider ◽  
Ranjita Shegokar ◽  
...  
Keyword(s):  
Intraperitoneal Chemotherapy ◽  
Glycolic Acid ◽  
Positive Charge ◽  
Tissue Concentration ◽  
Ex Vivo ◽  
Tissue Uptake ◽  
Electrostatic Precipitation ◽  
Tissue Penetration ◽  
Curcumin Nanoparticles ◽  
Positively Charged

Aims: To investigate the potential of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-PLGA-NPs), alone and with electrostatic precipitation, for improving tissue uptake during pressurized intraperitoneal aerosol chemotherapy (PIPAC). Methods: Positively and negatively charged CUR-PLGA-NPs were delivered as PIPAC into inverted bovine urinary bladders ex vivo. The experiment was repeated with the additional use of electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (electrostatic PIPAC). Results: Positively charged CUR-PLGA-NPs increased depth of tissue penetration by 81.5% and tissue concentration by 80%. Electrostatic precipitation further improved the uptake of positively charged CUR-PLGA-NPs by 41.8%. Conclusion: The combination of positive charge and electrostatic precipitation have significant potential to improve tissue uptake of nanoparticles during intraperitoneal chemotherapy.

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