Delivery Efficacy Differences of Intravenous and Intraperitoneal Injection of Exosomes: Perspectives from Tracking Dye Labeled and MiRNA Encapsulated Exosomes

2020 ◽  
Vol 17 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Xueying Zhou ◽  
Zhelong Li ◽  
Wenqi Sun ◽  
Guodong Yang ◽  
Changyang Xing ◽  
...  
Keyword(s):  
Intraperitoneal Injection ◽  
Drug Delivery Vehicles ◽  
C Elegans ◽  
Administration Routes ◽  
In Vivo Distribution ◽  
Obesity Therapy ◽  
Delivery Vehicles ◽  
Visceral Adipose ◽  
Mirna Abundance

Background: Exosomes are cell-derived nanovesicles that play vital roles in intercellular communication. Recently, exosomes are recognized as promising drug delivery vehicles. Up till now, how the in vivo distribution of exosomes is affected by different administration routes has not been fully understood. Methods: In the present study, in vivo distribution of exosomes following intravenous and intraperitoneal injection approaches was systemically analyzed by tracking the fluorescence-labeled exosomes and qPCR analysis of C. elegans specific miRNA abundance delivered by exosomes in different organs. Results: The results showed that exosomes administered through tail vein were mostly taken up by the liver, spleen and lungs while exosomes injected intraperitoneally were more dispersedly distributed. Besides the liver, spleen, and lungs, intraperitoneal injection effectively delivered exosomes into the visceral adipose tissue, making it a promising strategy for obesity therapy. Moreover, the results from fluorescence tracking and qPCR were slightly different, which could be explained by systemic errors. Conclusion: Together, our study reveals that different administration routes cause a significant differential in vivo distribution of exosomes, suggesting that optimization of the delivery route is prerequisite to obtain rational delivery efficiency in detailed organs.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

scholarly journals Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 427
Author(s):  
Amin Mirzaaghasi ◽  
Yunho Han ◽  
So-Hee Ahn ◽  
Chulhee Choi ◽  
Ji-Ho Park
Keyword(s):  
Drug Delivery ◽  
Therapeutic Potential ◽  
Hek293t Cell ◽  
Biological Properties ◽  
Context Analysis ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Diseased State ◽  
Sepsis And Septic Shock

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.

scholarly journals Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

2016 ◽  
Vol 113 (48) ◽  
pp. 13857-13862 ◽  
Author(s):  
Xinyi Jiang ◽  
Sergio Fitch ◽  
Christine Wang ◽  
Christy Wilson ◽  
Jianfeng Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Xenograft Model ◽  
Adipose Derived Stem Cells ◽  
Drug Delivery Vehicles ◽  
Effective Strategies ◽  
Polymeric Nanoparticle ◽  
Promising Therapeutic Approach ◽  
Delivery Vehicles ◽  
Necrosis Factor

Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strategies remain elusive. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as drug-delivery vehicles for targeting and eradicating GBM cells in vivo. Our results showed that polymeric nanoparticle-mediated transfection led to robust up-regulation of TRAIL in hADSCs, and that TRAIL-expressing hADSCs induced tumor-specific apoptosis. When transplanted in a mouse intracranial xenograft model of patient-derived glioblastoma cells, hADSCs exhibited long-range directional migration and infiltration toward GBM tumor. Importantly, TRAIL-overexpressing hADSCs inhibited GBM growth, extended survival, and reduced the occurrence of microsatellites. Repetitive injection of TRAIL-overexpressing hADSCs significantly prolonged animal survival compared with single injection of these cells. Taken together, our data suggest that nanoparticle-engineered TRAIL-expressing hADSCs exhibit the therapeutically relevant behavior of “seek-and-destroy” tumortropic migration and could be a promising therapeutic approach to improve the treatment outcomes of patients with malignant brain tumors.

scholarly journals Physicochemical characterization, toxicity and in vivo biodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin

2020 ◽  
Author(s):  
Maria Lyngaas Torgersen ◽  
Peter J. Judge ◽  
Juan F. Bada Juarez ◽  
Abhilash D. Pandya ◽  
Markus Fusser ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Physicochemical Characterization ◽  
Phospholipid Bilayer ◽  
Drug Delivery Vehicles ◽  
Carboxylate Groups ◽  
Biodistribution Studies ◽  
Aqueous Environments ◽  
Delivery Vehicles ◽  
Doxorubicin Release

AbstractMany promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

scholarly journals Biocompatible soft hydrogel lens as topical implants for diabetic retinopathy

2021 ◽  
Author(s):  
Rajkumar Sadasivam ◽  
Gopinath Packirisamy ◽  
Mayank Goswami
Keyword(s):  
Diabetic Retinopathy ◽  
Contact Lens ◽  
Contact Lenses ◽  
Research Work ◽  
Posterior Part ◽  
Ongoing Research ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Novel Drug

Fashioned contact lenses can be converted into a novel drug delivery vehicles. Ocular disease like diabetic retinopathy is a major microvascular complication where its early diagnosis and treatment is still a mystery to clinicians. Delivery of pharmaceuticals to the posterior part of eye is quite difficult, with exemption from the injectable formulations. Drug loaded hydrogel like contact lens implants can be utilized in place of commercial contact lens. Such hydrogel lens implants are developed with precise manner in which they are to be inserted as implants in the mice models. The present work is the preliminary outcome of our ongoing research work where the polymerized lens implant can be used as payload carrier for retinopathy. The aim is to propose such appropriate implants suitable for in vivo mice models.

scholarly journals Can nanotechnology potentiate photodynamic therapy?

2012 ◽  
Vol 1 (2) ◽  
pp. 111-146 ◽  
Author(s):  
Ying-Ying Huang ◽  
Sulbha K. Sharma ◽  
Tianhong Dai ◽  
Hoon Chung ◽  
Anastasia Yaroslavsky ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Plasmonic Enhancement ◽  
Gold And Silver Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Two Photon ◽  
Photon Excitation ◽  
Poorly Soluble ◽  
Delivery Vehicles

AbstractPhotodynamic therapy (PDT) uses the combination of nontoxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nanotechnology potentiate PDT?”

scholarly journals Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cynthia Aslan ◽  
Seyed Hossein Kiaie ◽  
Naime Majidi Zolbanin ◽  
Parisa Lotfinejad ◽  
Reihaneh Ramezani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Expression ◽  
Messenger Rnas ◽  
Drug Delivery Vehicles ◽  
New Class ◽  
The Past ◽  
Recent Developments ◽  
Cell Sources ◽  
Delivery Vehicles

AbstractOver the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.

scholarly journals Interplay of target site architecture and miRNA abundance determine miRNA activity and specificity

2017 ◽  
Author(s):  
Giovanna Brancati ◽  
Sarah H. Carl ◽  
Helge Großhans
Keyword(s):  
Mirna Family ◽  
Target Site ◽  
Site Quality ◽  
Seed Match ◽  
Base Pairs ◽  
Physiological Conditions ◽  
C Elegans ◽  
Mirna Seed ◽  
Mirna Abundance

ABSTRACTThe recognition that the miRNA seed sequence is a major determinant of miRNA activity has greatly advanced the ability to predict miRNA targets. However, it has remained unclear to what extent miRNAs act redundantly when they are members of the same family and thus share a common seed. Using in vivo studies in C. elegans, we uncover features that drive specific target repression by individual miRNA family members. We find that seed-distal complementarity to a specific family member promotes specificity. However, the extent and robustness of specificity are greatly increased by seed match ‘imperfections’, such as bulges and G:U wobble base pairs. Depending on the seed match architecture, specificity may be overcome by increasing the levels of a miRNA lacking seed-distal complementarity. Hence, in contrast to a binary distinction between functional and non-functional target sites, our data support a model where functionality depends on a combination of target site quality and miRNA abundance. This emphasizes the importance of studying miRNAs under physiological conditions in their endogenous contexts.

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