Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment.

Download Full-text

Exploring the drug loading mechanism of photoresponsive inorganic nanocarriers through molecular dynamics simulations

Nanoscale ◽

10.1039/d1nr01972d ◽

2021 ◽

Author(s):

Stefano Motta ◽

Paulo Siani ◽

Andrea Levy ◽

Cristiana Di Valentin

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Combine Therapy ◽

Drug Loading ◽

Drug Carriers ◽

Inorganic Nanoparticles ◽

Loading Capacity ◽

Physical Stimuli ◽

Dynamics Simulations

Inorganic nanoparticles are gaining increasing attention as drug carriers because they respond to external physical stimuli, allowing to combine therapy with diagnosis. Their drawback is a low drug loading capacity,...

Download Full-text

Nanosponge Approach -A Plethora Of Opportunities As A Promising Nanocarrier For Novel Drug Delivery

Recent Patents on Nanotechnology ◽

10.2174/1872210515666210720141736 ◽

2021 ◽

Vol 15 ◽

Author(s):

Shah Esha Bhavin ◽

Gajjar Anuradha

Keyword(s):

Drug Delivery ◽

Drug Loading ◽

Genetic Material ◽

Analytical Techniques ◽

Controlled Drug Release ◽

Drug Carriers ◽

Synthetic Methods ◽

Ongoing Research ◽

Factors Affecting ◽

Novel Drug

Background: Nanotechnology is the need of the hour! The design of nanotechnology aided carriers as a tool for the delivery of low solubility molecules offers a potential platform to overcome the issues of current clinical treatment and achieve good targeted release and bioaccessibility. Objective: Nanosponges (NS) are encapsulating type of nanocarriers capable of carrying both lipophilic and hydrophilic substances. They are synthesized by mixing a solution of polyester which is biodegradable with cross linkers. These tiny porous structures are round shaped having multiple cavities wherein drugs can be housed to offer programmable release. Method: The detailed literature review and patent search summarize the ongoing research on NS. Substances such as poorly soluble drugs, nutraceuticals, gases, proteins and peptides, volatile oils, genetic material, etc. can be loaded on these novel carriers, which are characterized using various analytical techniques. Target-specific drug delivery and controlled drug release are the advantages offered by NS along with a myriad of other promising applications. Results: This review stresses on the development of cyclodextrin based NS, the synthetic methods and characterization of NS along with factors affecting NS formation, their applications and information on the patented work in this area. NS are solid in character and can be formulated in various dosage forms such as parenteral, topical, oral or inhalation. Conclusion: Therefore, owing to their promising benefits over other nanocarriers in terms of drug loading, adaptability, sustainability, solubility and tailored release profile, NS are immediate technological revolution for drug entrapment and as novel drug carriers. The authors expect that these fundamental applications of NS could help the researchers to develop and gain insight about NS in novel drug delivery applications.

Download Full-text

Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00163-07 ◽

2007 ◽

Vol 51 (6) ◽

pp. 2156-2163 ◽

Cited By ~ 66

Author(s):

Iftach Yacoby ◽

Hagit Bar ◽

Itai Benhar

Keyword(s):

Staphylococcus Aureus ◽

Drug Loading ◽

Drug Carriers ◽

Health Concern ◽

Release Mechanism ◽

Toxic Substances ◽

Filamentous Bacteriophages ◽

Targeted Drug ◽

New Formulation ◽

Novel Drug

ABSTRACT While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug.

Download Full-text

Overview and Update on Methods for Cargo Loading into Extracellular Vesicles

Processes ◽

10.3390/pr9020356 ◽

2021 ◽

Vol 9 (2) ◽

pp. 356

Author(s):

Yohan Han ◽

Timothy W. Jones ◽

Saugata Dutta ◽

Yin Zhu ◽

Xiaoyun Wang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Extracellular Vesicles ◽

Delivery System ◽

Therapeutic Potential ◽

Drug Carriers ◽

Biological Information ◽

Therapeutic Drugs ◽

Loading Methods ◽

Novel Drug

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Growing evidence shows that EVs have great potential to serve as effective drug carriers. Since EVs can not only transfer biological information, but also effectively deliver hydrophobic drugs into cells, the application of EVs as a novel drug delivery system has attracted considerable scientific interest. Recently, EVs loaded with siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, or therapeutic drugs show improved delivery efficiency and drug effect. In this review, we summarize the methods used for the cargo loading into EVs, including siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, and therapeutic drugs. Furthermore, we also include the recent advance in engineered EVs for drug delivery. Finally, both advantages and challenges of EVs as a new drug delivery system are discussed. Here, we encourage researchers to further develop convenient and reliable loading methods for the potential clinical applications of EVs as drug carriers in the future.

Download Full-text

Advances in Anti-Tumor Nanomedicine based on Functional Metal Organic Frameworks beyond Drug Carriers

Journal of Materials Chemistry B ◽

10.1039/d1tb02518j ◽

2022 ◽

Author(s):

Qin Wei ◽

Yihan Wu ◽

Fangfang Liu ◽

Jiao Cao ◽

Jinliang Liu

Keyword(s):

Porous Structure ◽

Drug Loading ◽

Metal Organic Frameworks ◽

Structural Diversity ◽

Drug Carriers ◽

Loading Capacity ◽

High Drug ◽

Metal Organic ◽

Widespread Interest ◽

High Drug Loading

Nanoscale metal-organic frameworks (MOFs) have attracted widespread interest due to the unique properties including tunable porous structure, high drug loading capacity, structural diversity, and outstanding biocompatibility. MOFs have been extensively...

Download Full-text

Cytochalasin-B-Inducible Nanovesicle Mimics of Natural Extracellular Vesicles That Are Capable of Nucleic Acid Transfer

Micromachines ◽

10.3390/mi10110750 ◽

2019 ◽

Vol 10 (11) ◽

pp. 750 ◽

Cited By ~ 1

Author(s):

Oshchepkova ◽

Neumestova ◽

Matveeva ◽

Artemyeva ◽

Morozova ◽

...

Keyword(s):

Plasma Membrane ◽

Nucleic Acid ◽

Extracellular Vesicles ◽

Cytochalasin B ◽

Cell Communication ◽

Extracellular Vesicle ◽

Hek293 Cells ◽

Nucleic Acid Delivery ◽

Loading Capacity ◽

Oligonucleotide Delivery

Extracellular vesicles provide cell-to-cell communication and have great potential for use as therapeutic carriers. This study was aimed at the development of an extracellular vesicle-based system for nucleic acid delivery. Three types of nanovesicles were assayed as oligonucleotide carriers: mesenchymal stem cell-derived extracellular vesicles and mimics prepared either by cell treatment with cytochalasin B or by vesicle generation from plasma membrane. Nanovesicles were loaded with a DNA oligonucleotide by freezing/thawing, sonication, or permeabilization with saponin. Oligonucleotide delivery was assayed using HEK293 cells. Extracellular vesicles and mimics were characterized by a similar oligonucleotide loading level but different efficiency of oligonucleotide delivery. Cytochalasin-B-inducible nanovesicles exhibited the highest level of oligonucleotide accumulation in HEK293 cells and a loading capacity of 0.44 ± 0.05 pmol/µg. The loaded oligonucleotide was mostly protected from nuclease action.

Download Full-text

Nanoscale covalent organic frameworks as smart carriers for drug delivery

Chemical Communications ◽

10.1039/c6cc00853d ◽

2016 ◽

Vol 52 (22) ◽

pp. 4128-4131 ◽

Cited By ~ 189

Author(s):

Linyi Bai ◽

Soo Zeng Fiona Phua ◽

Wei Qi Lim ◽

Avijit Jana ◽

Zhong Luo ◽

...

Keyword(s):

Drug Delivery ◽

Sustained Release ◽

Drug Loading ◽

Drug Carriers ◽

Loading Capacity ◽

Covalent Organic Frameworks ◽

High Drug ◽

Good Biocompatibility ◽

High Drug Loading

Two nanoscale covalent organic frameworks as drug carriers with good biocompatibility were developed, showing high drug loading capacity and sustained release in vitro.

Download Full-text

Magnetic Driven Nanocarriers for pH-Responsive Doxorubicin Release in Cancer Therapy

Molecules ◽

10.3390/molecules25020333 ◽

2020 ◽

Vol 25 (2) ◽

pp. 333 ◽

Cited By ~ 2

Author(s):

João Nogueira ◽

Sofia F. Soares ◽

Carlos O. Amorim ◽

João S. Amaral ◽

Cláudia Silva ◽

...

Keyword(s):

Drug Delivery ◽

Iron Oxide ◽

Drug Loading ◽

Drug Carriers ◽

Release Profile ◽

Loading Capacity ◽

Drug Release Profile ◽

Blood Ph ◽

Alternative Drug ◽

Doxorubicin Release

Doxorubicin is one of the most widely used anti-cancer drugs, but side effects and selectivity problems create a demand for alternative drug delivery systems. Herein we describe a hybrid magnetic nanomaterial as a pH-dependent doxorubicin release carrier. This nanocarrier comprises magnetic iron oxide cores with a diameter of 10 nm, enveloped in a hybrid material made of siliceous shells and ĸ-carrageenan. The hybrid shells possess high drug loading capacity and a favorable drug release profile, while the iron oxide cores allows easy manipulation via an external magnetic field. The pH responsiveness was assessed in phosphate buffers at pH levels equivalent to those of blood (pH 7.4) and tumor microenvironment (pH 4.2 and 5). The nanoparticles have a loading capacity of up to 12.3 wt.% and a release profile of 80% in 5 h at acidic pH versus 25% at blood pH. In vitro drug delivery tests on human breast cancer and non-cancer cellular cultures have shown that, compared to the free drug, the loaded nanocarriers have comparable antiproliferative effect but a less intense cytotoxic effect, especially in the non-cancer cell line. The results show a clear potential for these new hybrid nanomaterials as alternative drug carriers for doxorubicin.

Download Full-text

Molecular Dynamic Simulation Study on Soy Protein As Drug Delivery Vehicle

Volume 3: Advanced Materials: Design, Processing, Characterization, and Applications ◽

10.1115/imece2020-23590 ◽

2020 ◽

Author(s):

Zhuoyuan Zheng ◽

Akash Singh ◽

Yumeng Li

Keyword(s):

Drug Delivery ◽

Soy Protein ◽

Active Sites ◽

Drug Loading ◽

Allyl Isothiocyanate ◽

Drug Carriers ◽

Van Der Waals Interactions ◽

Delivery Vehicle ◽

Drug Delivery Vehicle ◽

Polar Residues

Abstract Protein-based drug carriers are promising candidates for efficient drug delivery among the available potential colloidal carrier systems, due to their low cytotoxicity, abundance, renewability, diverse functional groups and interactions, and high drug loading capacity, etc. In this study, molecular dynamics (MD) simulations are performed to study the mechanisms of 11S molecule of soy protein as drug delivery vehicle to attach allyl isothiocyanate (AITC) and doxorubicin (DOX) drugs. The intermolecular interactions between protein and drugs are investigated; and the loading capacities of the protein molecules are calculated and compared with experiments. It is found that, for the AITC system, both nonpolar and polar residues of protein have the ability to adsorb AITCs; particularly, the polar residues serve as the primary active sites for the stable attachment of the drug molecules through the electrostatic (dipole-dipole) interactions. For the DOX system, however, the main driving force become the π-π stacking (the van der Waals interactions) among the aromatic rings of DOX and protein. In addition to pristine protein, different denaturation processes are found to be able to increase the exposure of active sites, therefore, enhance the loading efficiency of the protein carriers.

Download Full-text

Chemotherapy of Prostate Cancer by Targeted Nanoparticles Trackable by Magnetic Resonance Imaging

ISRN Nanotechnology ◽

10.5402/2012/407429 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Mohamed O. Abdalla ◽

Timothy Turner ◽

Clayton Yates

Keyword(s):

Prostate Cancer ◽

Drug Delivery ◽

Mr Imaging ◽

Drug Loading ◽

Drug Carriers ◽

The United States ◽

Amino Terminal ◽

Novel Drug ◽

Imaging Contrast Agent ◽

Amino Terminal Fragment

Prostate cancer (CaP) is the commonest diagnosed malignancy and the second main cause of cancer mortality in males in the United States. Thus, there is an urgent need to develop novel drug delivery systems to improve the chemotherapy option for CaP patients. The goal of this paper is to describe novel moleculary guided nanoscale drug delivery system with dual functionality for treatment and MR imaging of CaP. We describe the synthesis of iron oxide nanoparticles (IONPs) which are then coated with carboxyl-ended amphiphilic polymer. We present the protocol for tethering of the CaP targeting protein, human amino terminal fragment (hATF) to the terminal carboxyls of the IONPs. We describe the drug loading and release and the methods for measuring of the internalization of the hATF-guided IONPs into CaP cells. We also describe the methods for usages of IONPs are MR imaging contrast agent and successful targeted drug carriers.

Download Full-text