scholarly journals Magnetically Assisted Drug Delivery of Topical Eye Drops Maintains Retinal Function In Vivo in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1650
Author(s):  
Marco Bassetto ◽  
Daniel Ajoy ◽  
Florent Poulhes ◽  
Cathy Obringer ◽  
Aurelie Walter ◽  
...  
Keyword(s):  
Drug Targeting ◽  
Biological Effects ◽  
Genetic Disorder ◽  
Topical Administration ◽  
Magnetic Drug Targeting ◽  
Eye Drops ◽  
Non Invasive ◽  
Assisted Delivery ◽  
Magnetically Assisted

Barded-Biedl syndrome (BBS) is a rare genetic disorder with an unmet medical need for retinal degeneration. Small-molecule drugs were previously identified to slow down the apoptosis of photoreceptors in BBS mouse models. Clinical translation was not practical due to the necessity of repetitive invasive intravitreal injections for pediatric populations. Non-invasive methods of retinal drug targeting are a prerequisite for acceptable adaptation to the targeted pediatric patient population. Here, we present the development and functional testing of a non-invasive, topical, magnetically assisted delivery system, harnessing the ability of magnetic nanoparticles (MNPs) to cargo two drugs (guanabenz and valproic acid) with anti-unfolded protein response (UPR) properties towards the retina. Using magnetic resonance imaging (MRI), we showed the MNPs’ presence in the retina of Bbs wild-type mice, and their photoreceptor localization was validated using transmission electron microscopy (TEM). Subsequent electroretinogram recordings (ERGs) demonstrated that we achieved beneficial biological effects with the magnetically assisted treatment translating the maintained light detection in Bbs−/− mice (KO). To our knowledge, this is the first demonstration of efficient magnetic drug targeting in the photoreceptors in vivo after topical administration. This non-invasive, needle-free technology expands the application of SMDs for the treatment of a vast spectrum of retinal degenerations and other ocular diseases.

scholarly journals In Vivo Study on Magnetomotive Ultrasound Imaging in the Framework of Nanoparticle based Magnetic Drug Targeting

2020 ◽  
Vol 6 (3) ◽  
pp. 543-546
Author(s):  
Michael Fink ◽  
Stefan J. Rupitsch ◽  
Helmut Ermert ◽  
Stefan Lyer
Keyword(s):  
Iron Oxide ◽  
Magnetic Nanoparticles ◽  
Drug Targeting ◽  
Imaging Technique ◽  
Small Animal ◽  
Magnetic Drug Targeting ◽  
Oxide Nanoparticles ◽  
Medical Procedures ◽  
First Time

AbstractVarious medical procedures make use of magnetic nanoparticles, such as Magnetic Drug Targeting (MDT), which boosts the demand for imaging modalities that are capable of in vivo visualizing this kind of particles. Magnetomotive Ultrasound is an imaging technique that can detect tissue, which is perfused by magnetic nanoparticles. In this contribution, we investigate the suitability of Magnetomotive Ultrasound to serve as a monitoring system during MDT. With the conducted measurements, it was possible for the first time to observe in vivo the accumulation of iron-oxide nanoparticles during a Magnetic Drug Targeting cancer treatment applied to a small animal (rabbit).

scholarly journals New Insights into the Mechanisms of Action of Topical Administration of GLP-1 in an Experimental Model of Diabetic Retinopathy

2019 ◽  
Vol 8 (3) ◽  
pp. 339 ◽  
Author(s):  
Joel Sampedro ◽  
Patricia Bogdanov ◽  
Hugo Ramos ◽  
Cristina Solà-Adell ◽  
Mireia Turch ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Neurovascular Unit ◽  
Topical Administration ◽  
Inflammatory Factors ◽  
Eye Drops ◽  
Beneficial Effects ◽  
Apoptotic Protein ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms

The main goals of this work were to assess whether the topical administration of glucagon-like peptide-1 (GLP-1) could revert the impairment of the neurovascular unit induced by long-term diabetes (24 weeks) in diabetic mice and to look into the underlying mechanisms. For that reason, db/db mice were treated with eye drops of GLP-1 or vehicle for 3 weeks. Moreover, db/+ mice were used as control. Studies performed in vivo included electroretinogramand the assessment of vascular leakage by using Evans Blue. NF-κB, GFAP and Ki67 proteins were analyzed by immunofluorescence (IF). Additionally, caspase 9, AMPK, IKBα, NF-κB, AKT, GSK3, β-catenin, Bcl-xl, and VEGF were analyzed by WB. Finally, VEGF, IL-1β, IL-6, TNF-α, IL-18, and NLRP3 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. We found that topical administration of GLP-1 reverted reactive gliosis and albumin extravasation, and protected against apoptosis and retinal dysfunction. Regarding the involved mechanisms, GLP-1 exerted an anti-inflammatory action by decreasing NF-κB, inflammosome, and pro-inflammatory factors. In addition, it also decreased VEGF expression. Furthermore, GLP-1 promoted cell survival by increasing the anti-apoptotic protein Bcl-xl and the signaling pathway Akt/GSK3b/β-catenin. Finally, Ki67 results revealed that GLP-1 treatment could induce neurogenesis. In conclusion, the topical administration of GLP-1 reverts the impairment of the neurovascular unit by modulating essential pathways involved in the development of diabetic retinopathy (DR). These beneficial effects on the neurovascular unit could pave the way for clinical trials addressed to confirm the effectiveness of GLP-1 in early stages of DR.

scholarly journals In vivo non-invasive monitoring of dystrophin correction in a new Duchenne muscular dystrophy reporter mouse

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Leonela Amoasii ◽  
Hui Li ◽  
Yu Zhang ◽  
Yi-Li Min ◽  
Efrain Sanchez-Ortiz ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Genetic Disorder ◽  
Dystrophin Gene ◽  
Luciferase Reporter ◽  
Luciferase Expression ◽  
Gene Correction ◽  
Reading Frame ◽  
Non Invasive

Abstract Duchenne muscular dystrophy (DMD) is a fatal genetic disorder caused by mutations in the dystrophin gene. To enable the non-invasive analysis of DMD gene correction strategies in vivo, we introduced a luciferase reporter in-frame with the C-terminus of the dystrophin gene in mice. Expression of this reporter mimics endogenous dystrophin expression and DMD mutations that disrupt the dystrophin open reading frame extinguish luciferase expression. We evaluated the correction of the dystrophin reading frame coupled to luciferase in mice lacking exon 50, a common mutational hotspot, after delivery of CRISPR/Cas9 gene editing machinery with adeno-associated virus. Bioluminescence monitoring revealed efficient and rapid restoration of dystrophin protein expression in affected skeletal muscles and the heart. Our results provide a sensitive non-invasive means of monitoring dystrophin correction in mouse models of DMD and offer a platform for testing different strategies for amelioration of DMD pathogenesis.

scholarly journals Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1127
Author(s):  
Massimo Fresta ◽  
Antonia Mancuso ◽  
Maria Chiara Cristiano ◽  
Konrad Urbanek ◽  
Felisa Cilurzo ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Biological Effects ◽  
Biological Response ◽  
Response Duration ◽  
Topical Administration ◽  
Active Compounds ◽  
Biological Responses ◽  
Negative Surface

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

Quantification of Magnetic Nanoparticles by Magnetorelaxometry and Comparison to Histology After Magnetic Drug Targeting

2006 ◽  
Vol 6 (9) ◽  
pp. 3222-3225 ◽  
Author(s):  
F. Wiekhorst ◽  
C. Seliger ◽  
R. Jurgons ◽  
U. Steinhoff ◽  
D. Eberbeck ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Cross Sections ◽  
Drug Targeting ◽  
Magnetic Particles ◽  
Particle Distribution ◽  
Drug Carrier ◽  
Magnetic Drug Targeting ◽  
Tissue Samples ◽  
Drug Carrier System

Magnetic nanoparticles can be used in medicine in vivo as contrast agents and as a drug carrier system for chemotherapeutics. Thus local cancer therapy is performed with Magnetic Drug Targeting (MDT) and allows a specific delivery of therapeutic agents to desired targets, i.e., tumors, by using a chemotherapeutic substance bound to magnetic nanoparticles and focused with an external magnetic field to the tumor after intraarterial application. Important for this therapeutic principle is the distribution of the particles in the whole organism and especially in the tumor. Therefore we used magnetorelaxometry to quantify ferrofluids delivered after MDT. Tissue samples of some mm3 volume of a VX2 squamous cell carcinoma were measured by magnetic relaxation and the amount of iron was determined using the original ferrofluid suspension as a reference. From this the distribution of the magnetic particles within the slice of tumor was reconstructed. Histological cross-sections of the respective tumor offer the opportunity to map quantitatively the particle distribution and the vascularisation in the targeted tumor on a microscopic scale. Our data show that the integral method magnetorelaxometry and microscopic histological methods can complete each other efficiently.

scholarly journals Harmonisation of multi-site MRS data with ComBat

2021 ◽  
Author(s):  
Tiffany K Bell ◽  
Kate J Godfrey ◽  
Ashley L Ware ◽  
Keith Owen Yeates ◽  
Ashley DK Harris
Keyword(s):  
Neurological Disorders ◽  
Biological Effects ◽  
Resonance Spectroscopy ◽  
Biological Variability ◽  
Non Invasive ◽  
Standard Press ◽  
Biological Sources ◽  
Using Data ◽  
Data Harmonisation

Magnetic resonance spectroscopy (MRS) is a non-invasive neuroimaging technique used to measure brain chemistry in vivo and has been used to study the healthy brain as well as neuropathology in numerous neurological disorders. The number of multi-site studies using MRS are increasing; however, non-biological variability introduced during data collection across multiple sites, such as differences in scanner vendors and site-specific acquisition implementations for MRS, can obscure detection of biological effects of interest. ComBat is a data harmonisation technique that can remove non-biological sources of variance in multisite studies. It has been validated for use with structural and functional MRI metrics but not for MRS metabolites. This study investigated the validity of using ComBat to harmonize MRS metabolites for vendor and site differences. Analyses were performed using data acquired across 20 sites and included edited MRS for GABA+ (N=218) and macromolecule-suppressed GABA data (N=209), as well as standard PRESS data to quantify NAA, creatine, choline, and glutamate (N=195). ComBat harmonisation successfully mitigated vendor and site differences for all metabolites of interest. Moreover, significant associations were detected between sex and choline levels and between age and glutamate and GABA+ levels that were not detectable prior to harmonisation, confirming the importance of removing site and vendor effects in multi-site data. In conclusion, ComBat harmonisation can be successfully applied to MRS data in multi-site MRS studies.

scholarly journals Strategies to Improve Resveratrol Systemic and Topical Bioavailability: An Update

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 244 ◽  
Author(s):  
Sebastiano Intagliata ◽  
Maria N. Modica ◽  
Ludovica M. Santagati ◽  
Lucia Montenegro
Keyword(s):  
Water Solubility ◽  
Biological Activities ◽  
Biological Effects ◽  
Radical Scavenging ◽  
Topical Administration ◽  
In Vivo Studies ◽  
Biochemical Mechanisms ◽  
Free Radical Scavenging Activities

In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.

scholarly journals Nonviral Locally Injected Magnetic Vectors for In Vivo Gene Delivery: A Review of Studies on Magnetofection

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1078
Author(s):  
Artem A. Sizikov ◽  
Marianna V. Kharlamova ◽  
Maxim P. Nikitin ◽  
Petr I. Nikitin ◽  
Eugene L. Kolychev
Keyword(s):  
Magnetic Field ◽  
Magnetic Nanoparticles ◽  
Gene Delivery ◽  
Drug Targeting ◽  
Genetic Material ◽  
Magnetic Drug Targeting ◽  
Local Injections ◽  
In Vivo Gene Delivery ◽  
Magnetic Vectors

Magnetic nanoparticles have been widely used in nanobiomedicine for diagnostics and the treatment of diseases, and as carriers for various drugs. The unique magnetic properties of “magnetic” drugs allow their delivery in a targeted tumor or tissue upon application of a magnetic field. The approach of combining magnetic drug targeting and gene delivery is called magnetofection, and it is very promising. This method is simple and efficient for the delivery of genetic material to cells using magnetic nanoparticles controlled by an external magnetic field. However, magnetofection in vivo has been studied insufficiently both for local and systemic routes of magnetic vector injection, and the relevant data available in the literature are often merely descriptive and contradictory. In this review, we collected and systematized the data on the efficiency of the local injections of magnetic nanoparticles that carry genetic information upon application of external magnetic fields. We also investigated the efficiency of magnetofection in vivo, depending on the structure and coverage of magnetic vectors. The perspectives of the development of the method were also considered.

scholarly journals Dry Tablet Formulation of PLGA Nanoparticles with a Preocular Applicator for Topical Drug Delivery to the Eye

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 651 ◽  
Author(s):  
Woo Mi Ryu ◽  
Se-Na Kim ◽  
Chang Hee Min ◽  
Young Bin Choy
Keyword(s):  
Fold Increase ◽  
Topical Administration ◽  
Plga Nanoparticles ◽  
Drug Dose ◽  
Eye Drops ◽  
Drug Bioavailability ◽  
Sustained Drug Release ◽  
Accurate Dose ◽  
Viscosity Enhancement

To enhance ocular drug bioavailability, a rapidly dissolving dry tablet containing alginate and drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles was proposed. For hygienic and easy administration of an accurate drug-dose with this tablet, the use of a preocular applicator was suggested. Herein, a dry tablet was prepared by embedding dexamethasone-loaded PLGA nanoparticles in alginate, which was deposited on the tip of the applicator. The nanoparticles were loaded with 85.45 μg/mg drug and exhibited sustained drug release for 10 h. To evaluate in vivo efficacy, dexamethasone concentration in the aqueous humor was measured after topical administration of the dry tablet, with the applicator, to rabbit eyes and was compared to that achieved with Maxidex®, a commercially-available dexamethasone eye drops. When applied with the preocular applicator, the dry tablet containing alginate could be fully detached and delivered to the eye surface. In fact, it showed up to 2 h of nanoparticle retention on the preocular surface due to tear viscosity enhancement, causing an estimated 2.6-fold increase in ocular drug bioavailability compared to Maxidex®. Therefore, the preocular applicator combined with a dry alginate tablet containing PLGA nanoparticles can be a promising system for aseptically delivering an accurate dose of ophthalmic drug with enhanced bioavailability.

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