scholarly journals Engineering a virus-like particle to display peptide insertions using an apparent fitness landscape

2020 ◽  
Author(s):  
Stephanie A. Robinson ◽  
Emily C. Hartman ◽  
Bon C. Ikwuagwu ◽  
Matthew B. Francis ◽  
Danielle Tullman-Ercek
Keyword(s):  
Coat Protein ◽  
Fitness Landscape ◽  
Cell Uptake ◽  
Cell Binding ◽  
Drug Delivery Vehicles ◽  
Virus Like Particle ◽  
Viral Structure ◽  
Multiple Copies ◽  
Delivery Vehicles ◽  
Peptide Insertion

ABSTRACTPeptide insertions in the primary sequence of proteins expand functionality by introducing new binding sequences, chemical handles, or membrane disrupting motifs. With these properties, proteins can be engineered as scaffolds for vaccines or targeted drug delivery vehicles. Virus-like particles (VLPs) are promising platforms for these applications since they are genetically simple, mimic viral structure for cell uptake, and can deliver multiple copies of a therapeutic agent to a given cell. Peptide insertions in the coat protein of VLPs can increase VLP uptake in cells by increasing cell binding, but it is difficult to predict how an insertion affects monomer folding and higher order assembly. To this end, we have engineered the MS2 VLP using a high-throughput technique, called Systematic Mutagenesis and Assembled Particle Selection (SyMAPS). In this work, we applied SyMAPS to investigate a highly mutable loop in the MS2 coat protein to display 9,261 non-native tripeptide insertions. This library generates a discrete map of three amino acid insertions permitted at this location, validates the FG loop as a valuable position for peptide insertion, and illuminates how properties such as charge, flexibility, and hydrogen bonding can interact to preserve or disrupt capsid assembly. Taken together, the results highlight the potential to engineer VLPs in systematic manner, paving the way to exploring the applications of peptide insertions in biomedically relevant settings.

scholarly journals BSA Nanoparticles for siRNA Delivery: Coating Effects on Nanoparticle Properties, Plasma Protein Adsorption, andIn VitrosiRNA Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Haran Yogasundaram ◽  
Markian Stephan Bahniuk ◽  
Harsh-Deep Singh ◽  
Hamidreza Montezari Aliabadi ◽  
Hasan Uludaǧ ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Adsorption ◽  
Sirna Delivery ◽  
Cell Uptake ◽  
Drug Delivery Vehicles ◽  
Therapeutic Molecules ◽  
Delivery Vehicles ◽  
Active Research ◽  
Poly Ethylene

Developing vehicles for the delivery of therapeutic molecules, like siRNA, is an area of active research. Nanoparticles composed of bovine serum albumin, stabilizedviathe adsorption of poly-L-lysine (PLL), have been shown to be potentially inert drug-delivery vehicles. With the primary goal of reducing nonspecific protein adsorption, the effect of using comb-type structures of poly(ethylene glycol) (1 kDa, PEG) units conjugated to PLL (4.2 and 24 kDa) on BSA-NP properties, apparent siRNA release rate, cell viability, and cell uptake were evaluated. PEGylated PLL coatings resulted in NPs withζ-potentials close to neutral. Incubation with platelet-poor plasma showed the composition of the adsorbed proteome was similar for all systems. siRNA was effectively encapsulated and released in a sustained manner from all NPs. With 4.2 kDa PLL, cellular uptake was not affected by the presence of PEG, but PEG coating inhibited uptake with 24 kDa PLL NPs. Moreover, 24 kDa PLL systems were cytotoxic and this cytotoxicity was diminished upon PEG incorporation. The overall results identified a BSA-NP coating structure that provided effective siRNA encapsulation while reducingζ-potential, protein adsorption, and cytotoxicity, necessary attributes forin vivoapplication of drug-delivery vehicles.

Nanoscale Functional Biomaterials for Cancer Theranostics

2018 ◽  
Vol 25 (25) ◽  
pp. 2987-3000 ◽  
Author(s):  
Linying Liu ◽  
Xiaoshuang Li ◽  
Lei Chen ◽  
Xin Zhang
Keyword(s):  
Brain Cancer ◽  
Molecular Level ◽  
Functional Materials ◽  
Therapeutic Agents ◽  
Lower Side ◽  
Drug Delivery Vehicles ◽  
Functional Nanoparticles ◽  
Delivery Vehicles ◽  
Functional Biomaterials ◽  
Cancer Theranostics

Nanomedicine is widely developed in recent years. In nanomedicine system, nanoscale and nanostructured functional materials are used to manipulate the human biology systems at the molecular level for cancer imaging and therapy. New nanostructure based functional materials consist of nanoscale liposomes, spheres, micelles, capsules, emulsion, suspension and phamacosomes. Several functional nanoparticles such as lipidbased and polymer-based materials are demonstrated to be drug delivery vehicles and imaging agents. These materials are biodegradable, biocompatible and have better biodistribution, lower side effect and lower toxicity. In addition, hybrids with these materials coating provide uniquely electrical, optical and magnetic properties. This review discusses the research on the applications of functional materials, especially nanoparticles as imaging contrast agents, cancer therapeutic agents and multi-functional agents and this review focused on the theranostic integration treatments on liver cancer and brain cancer.

Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/Drug-delivery Vehicles in Current Medicine

2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
General Aspects

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.

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.

Exploring Nanoemulsion for Liver Cancer Therapy

2020 ◽  
Vol 16 (4) ◽  
pp. 260-268
Author(s):  
Tanmay Upadhyay ◽  
Vaseem A. Ansari ◽  
Usama Ahmad ◽  
Nazneen Sultana ◽  
Juber Akhtar
Keyword(s):  
Cancer Therapy ◽  
Liver Cancer ◽  
Treatment Plan ◽  
Chemotherapeutic Drugs ◽  
Drug Delivery Vehicles ◽  
Chronic Hepatitis B Virus ◽  
Anti Cancer ◽  
B Virus ◽  
Delivery Vehicles ◽  
Liquid Dosage Form

Cancer is a leading cause of mortality worldwide, accounting for 8.8 million deaths in 2015. Among these, at least 0.78 million people died of liver cancer alone. The recognized risk factors for liver cancer include chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, exposure to dietary aflatoxin, fatty liver disease, alcohol-induced cirrhosis, obesity, smoking, diabetes, and iron overload. The treatment plan for early diagnosed patients includes radiation therapy, tumour ablation, surgery, immunotherapy, and chemotherapy. Some sort of drug delivery vehicles has to be used when the treatment plan is targeted chemotherapy. Nanoemulsions are a class of biphasic liquid dosage form which are mixtures of oil and water stabilized by a surfactant. They are either transparent or bluish in hue and serve as a wonderful carrier system for chemotherapeutic drugs. These vehicles have a particle size in the range of 20-200 nm allowing them to be delivered successfully in the deepest of tissues. Recent publications on nanoemulsions reveal their acceptance and a popular choice for delivering both synthetic and herbal drugs to the liver. This work focuses on some anti-cancer agents that utilized the advantages of nanoemulsion for liver cancer therapy.

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 Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3589
Author(s):  
Rui Liu ◽  
Alessandro Poma
Keyword(s):  
Drug Delivery ◽  
Molecularly Imprinted Polymers ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
Molecularly Imprinted ◽  
Imprinted Polymers ◽  
Drug Delivery Vehicles ◽  
The Past ◽  
Drug Molecules ◽  
Delivery Vehicles

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.

scholarly journals A Review on Allopathic and Herbal Nanofibrous Drug Delivery Vehicles for Cancer Treatments

2021 ◽  
pp. e00663
Author(s):  
Tarun Mateti ◽  
Surabhi Aswath ◽  
Anoop Kishore Vatti ◽  
Agneya Kamath ◽  
Anindita Laha
Keyword(s):  
Drug Delivery ◽  
Cancer Treatments ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles
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