Dual-responsive biohybrid neutrobots for active target delivery

2021 ◽  
Vol 6 (52) ◽  
pp. eaaz9519 ◽  
Author(s):  
Hongyue Zhang ◽  
Zesheng Li ◽  
Changyong Gao ◽  
Xinjian Fan ◽  
Yuxin Pang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
The Body ◽  
Rotating Magnetic Field ◽  
Inflammatory Factors ◽  
Exciting Field ◽  
E Coli ◽  
Dual Responsive ◽  
Current Cell ◽  
Traditional Drug

Swimming biohybrid microsized robots (e.g., bacteria- or sperm-driven microrobots) with self-propelling and navigating capabilities have become an exciting field of research, thanks to their controllable locomotion in hard-to-reach areas of the body for noninvasive drug delivery and treatment. However, current cell-based microrobots are susceptible to immune attack and clearance upon entering the body. Here, we report a neutrophil-based microrobot (“neutrobot”) that can actively deliver cargo to malignant glioma in vivo. The neutrobots are constructed through the phagocytosis of Escherichia coli membrane-enveloped, drug-loaded magnetic nanogels by natural neutrophils, where the E. coli membrane camouflaging enhances the efficiency of phagocytosis and also prevents drug leakage inside the neutrophils. With controllable intravascular movement upon exposure to a rotating magnetic field, the neutrobots could autonomously aggregate in the brain and subsequently cross the blood-brain barrier through the positive chemotactic motion of neutrobots along the gradient of inflammatory factors. The use of such dual-responsive neutrobots for targeted drug delivery substantially inhibits the proliferation of tumor cells compared with traditional drug injection. Inheriting the biological characteristics and functions of natural neutrophils that current artificial microrobots cannot match, the neutrobots developed in this study provide a promising pathway to precision biomedicine in the future.

Nanostructured Ketorolac-Tromethamine/MCF: Synthesis, Characterization and Application in Drug Release System

2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Controlled Drug Release ◽  
Delivery Systems ◽  
The Body ◽  
Fickian Diffusion ◽  
Ketorolac Tromethamine

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.

scholarly journals Advances in Hybrid Polymer-Based Materials for Sustained Drug Release

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Lígia N. M. Ribeiro ◽  
Ana C. S. Alcântara ◽  
Gustavo H. Rodrigues da Silva ◽  
Michelle Franz-Montan ◽  
Silvia V. G. Nista ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Toxicity ◽  
Drug Delivery Systems ◽  
Hybrid Polymer ◽  
Future Perspectives ◽  
Sustained Drug Release ◽  
Physicochemical Stability ◽  
Traditional Drug

The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS) have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

scholarly journals Potential Toxicity of Iron Oxide Magnetic Nanoparticles: A Review

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3159 ◽  
Author(s):  
Nemi Malhotra ◽  
Jiann-Shing Lee ◽  
Rhenz Alfred D. Liman ◽  
Johnsy Margotte S. Ruallo ◽  
Oliver B. Villaflores ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Iron Oxide ◽  
Magnetic Nanoparticles ◽  
Cell Lines ◽  
Current Knowledge ◽  
Volume Ratio ◽  
The Body ◽  
Toxic Effects ◽  
Iron Oxide Magnetic Nanoparticles

The noteworthy intensification in the development of nanotechnology has led to the development of various types of nanoparticles. The diverse applications of these nanoparticles make them desirable candidate for areas such as drug delivery, coasmetics, medicine, electronics, and contrast agents for magnetic resonance imaging (MRI) and so on. Iron oxide magnetic nanoparticles are a branch of nanoparticles which is specifically being considered as a contrast agent for MRI as well as targeted drug delivery vehicles, angiogenic therapy and chemotherapy as small size gives them advantage to travel intravascular or intracavity actively for drug delivery. Besides the mentioned advantages, the toxicity of the iron oxide magnetic nanoparticles is still less explored. For in vivo applications magnetic nanoparticles should be nontoxic and compatible with the body fluids. These particles tend to degrade in the body hence there is a need to understand the toxicity of the particles as whole and degraded products interacting within the body. Some nanoparticles have demonstrated toxic effects such inflammation, ulceration, and decreases in growth rate, decline in viability and triggering of neurobehavioral alterations in plants and cell lines as well as in animal models. The cause of nanoparticles’ toxicity is attributed to their specific characteristics of great surface to volume ratio, chemical composition, size, and dosage, retention in body, immunogenicity, organ specific toxicity, breakdown and elimination from the body. In the current review paper, we aim to sum up the current knowledge on the toxic effects of different magnetic nanoparticles on cell lines, marine organisms and rodents. We believe that the comprehensive data can provide significant study parameters and recent developments in the field. Thereafter, collecting profound knowledge on the background of the subject matter, will contribute to drive research in this field in a new sustainable direction.

Vascular Nanomedicine: Current Status, Opportunities, and Challenges

2019 ◽  
Vol 46 (05) ◽  
pp. 524-544 ◽  
Author(s):  
Michael Sun ◽  
Anirban Sen Gupta
Keyword(s):  
Drug Delivery ◽  
Vascular Diseases ◽  
The Body ◽  
Current Status ◽  
Therapeutic Effects ◽  
Current State ◽  
Challenges And Opportunities ◽  
Disease Site ◽  
Drug Pharmacokinetics

AbstractThe term “nanotechnology” was coined by Norio Taniguchi in the 1970s to describe the manipulation of materials at the nano (10−9) scale, and the term “nanomedicine” was put forward by Eric Drexler and Robert Freitas Jr. in the 1990s to signify the application of nanotechnology in medicine. Nanomedicine encompasses a variety of systems including nanoparticles, nanofibers, surface nano-patterning, nanoporous matrices, and nanoscale coatings. Of these, nanoparticle-based applications in drug formulations and delivery have emerged as the most utilized nanomedicine system. This review aims to present a comprehensive assessment of nanomedicine approaches in vascular diseases, emphasizing particle designs, therapeutic effects, and current state-of-the-art. The expected advantages of utilizing nanoparticles for drug delivery stem from the particle's ability to (1) protect the drug from plasma-induced deactivation; (2) optimize drug pharmacokinetics and biodistribution; (3) enhance drug delivery to the disease site via passive and active mechanisms; (4) modulate drug release mechanisms via diffusion, degradation, and other unique stimuli-triggered processes; and (5) biodegrade or get eliminated safely from the body. Several nanoparticle systems encapsulating a variety of payloads have shown these advantages in vascular drug delivery applications in preclinical evaluation. At the same time, new challenges have emerged regarding discrepancy between expected and actual fate of nanoparticles in vivo, manufacturing barriers of complex nanoparticle designs, and issues of toxicity and immune response, which have limited successful clinical translation of vascular nanomedicine systems. In this context, this review will discuss challenges and opportunities to advance the field of vascular nanomedicine.

scholarly journals Advanced characterizations of nanoparticles for drug delivery: investigating their properties through the techniques used in their evaluations

2017 ◽  
Vol 6 (4) ◽  
pp. 355-372 ◽  
Author(s):  
Syed Mahmood ◽  
Uttam Kumar Mandal ◽  
Bappaditya Chatterjee ◽  
Muhammad Taher
Keyword(s):  
Drug Delivery ◽  
Advanced Characterization ◽  
Data Interpretation ◽  
Review Article ◽  
The Body ◽  
Drug Molecule ◽  
Drug Molecules ◽  
Preparation Techniques

AbstractNanomedicine has achieved a huge success in delivering a wide variety of drug molecules into the target site of the body. In this respect, the characterization of nanoformulation is very important to investigate the drug molecule together with its carrier as a nanoform during formulation, storage, and in vivo transport through the body. This review article summarizes important advanced characterization techniques of nanoformulation with respect to their theories, use of required instrumental parameters, sample preparation techniques, data interpretation, etc., to exploit them for the best possible results. This review article also sheds a glimpse to the shortcomings of these techniques together with further advancements required in future.

ATP/pH Dual Responsive Nanoparticle withd-[des-Arg10]Kallidin Mediated Efficient In Vivo Targeting Drug Delivery

Small ◽  
2016 ◽  
Vol 13 (3) ◽  
pp. 1602494 ◽  
Author(s):  
Yu Zhang ◽  
Yifei Lu ◽  
Feng Wang ◽  
Sai An ◽  
Yujie Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Dual Responsive

NANOMEDICINES: DELIVERING DRUGS USING BOTTOM UP NANOTECHNOLOGY

2005 ◽  
Vol 04 (05n06) ◽  
pp. 855-861 ◽  
Author(s):  
MARTIN GARNETT
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Biodegradable Polymers ◽  
Drug Loading ◽  
Dna Delivery ◽  
Delivery Systems ◽  
The Body ◽  
Nanosized Materials

The use of nanosized materials changes the way in which drugs are handled by the body and offers opportunities to improve drug delivery. The physiological mechanisms controlling the distribution of nanosized materials (enhanced permeability and retention effect, cellular uptake pathways and opsonisation/elimination of nanoparticles) are described. Two different nanosized drug delivery systems are considered; drug delivery and DNA delivery. The deficiencies of currently available biodegradable polymers for preparation of drug containing nanoparticles are mainly the amount of drug that can be incorporated and the rapid rate of drug release. The development of new biodegradable polymers which can interact with the drug and so significantly increase drug loading and decrease the rate of drug release are outlined. DNA delivery necessitates overcoming a variety of biological barriers. We are developing polyelectrolyte complexes of DNA with cationic polyamidoamines (PAA) as a delivery system. Complexing PAA with DNA results in good transfection of cells in vitro. However, in vivo, a more complex arrangement of PAA, Polyethylene glycol-PAA copolymers, DNA and the use of ligands will be required. Despite these efforts, further developments will be needed in nanotechnology for both drug and DNA nanoparticle delivery systems to achieve our clinical objectives.

scholarly journals Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization

2021 ◽  
Vol 12 ◽  
Author(s):  
Nuria Carpena ◽  
Kerry Richards ◽  
Teresita D. J. Bello Gonzalez ◽  
Alberto Bravo-Blas ◽  
Nicholas G. Housden ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Delivery ◽  
Controlled Release ◽  
Animal Models ◽  
Targeted Delivery ◽  
Intestinal Colonization ◽  
Ph Responsive ◽  
Human Gut ◽  
E Coli

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.

scholarly journals Micro/Nanorobot: A Promising Targeted Drug Delivery System

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 665 ◽  
Author(s):  
Mengyi Hu ◽  
Xuemei Ge ◽  
Xuan Chen ◽  
Wenwei Mao ◽  
Xiuping Qian ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Electric Fields ◽  
Targeted Drug Delivery ◽  
Disease Diagnosis ◽  
Research Field ◽  
Traditional Drug ◽  
Targeted Drug ◽  
Autonomous Movement

Micro/nanorobot, as a research field, has attracted interest in recent years. It has great potential in medical treatment, as it can be applied in targeted drug delivery, surgical operation, disease diagnosis, etc. Differently from traditional drug delivery, which relies on blood circulation to reach the target, the designed micro/nanorobots can move autonomously, which makes it possible to deliver drugs to the hard-to-reach areas. Micro/nanorobots were driven by exogenous power (magnetic fields, light energy, acoustic fields, electric fields, etc.) or endogenous power (chemical reaction energy). Cell-based micro/nanorobots and DNA origami without autonomous movement ability were also introduced in this article. Although micro/nanorobots have excellent prospects, the current research is mainly based on in vitro experiments; in vivo research is still in its infancy. Further biological experiments are required to verify in vivo drug delivery effects of micro/nanorobots. This paper mainly discusses the research status, challenges, and future development of micro/nanorobots.

Bioinspired Drug Delivery Carrier for Enhanced Tumor-Targeting in Melanoma Mice Model

2019 ◽  
Vol 15 (7) ◽  
pp. 1482-1491 ◽  
Author(s):  
Xu Wang ◽  
Gao-Feng Liang ◽  
Xue-Qin Hao ◽  
Shu-Ying Feng ◽  
Lu Dai ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Imaging System ◽  
Morphological Changes ◽  
The Body ◽  
Control Group ◽  
Mice Model ◽  
Normal Tissues ◽  
Specific Distribution

As a widely used first-line chemotherapy drug for tumor, Doxorubicin (DOX) can induce various side effects on normal tissues because of its non-specific distribution in the body. Emerging evidence has shown that platelets have the capability to recognize and interact with tumor cells. Inspired by this, the platelet-based drug delivery system was constructed by loading of DOX in platelet cytoplasm and modification of transferrin on the surface of platelet (Tf-P-DOX). The encapsulation efficiency of DOX in platelet was the highest at the DOX concentration of 0.05 mM, and reached to 64.9%. Fluorescence microscopy showed that the Tf-P-DOX facilitated cell uptakes and enhanced intracellular drug accumulation in B16F10 cells. Compared with free DOX, Tf-P-DOX exhibited an enhanced effect on cell apoptosis at the same concentration of DOX. In vivo imaging system showed that the near-infrared fluorescence of B16F10 tumor-bearing mice was mainly accumulated in the tumor site, which caused the inhibition of tumor growth in mice. The morphological changes of tumor tissue in Tf-P-DOX group was significant in comparison with those of the control group, including the small nucleus, the insufficiency of cancerous nest, and the infiltration of inflammatory cells, while Tf-P-DOX did not show significant adverse effects on normal tissues. Compared with the control group, the levels of caspase 9 and caspase 3 protein expressions were increased significantly in Tf-P-DOX group. Our studies suggest platelets can be repurposed as promising carriers for efficient targeting and treatment of solid tumors.

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