scholarly journals IRONSperm: Sperm-templated soft magnetic microrobots

2020 ◽  
Vol 6 (28) ◽  
pp. eaba5855 ◽  
Author(s):  
Veronika Magdanz ◽  
Islam S. M. Khalil ◽  
Juliane Simmchen ◽  
Guilherme P. Furtado ◽  
Sumit Mohanty ◽  
...  
Keyword(s):  
Self Assembly ◽  
Drug Loading ◽  
Chemotherapeutic Agents ◽  
Single Step ◽  
Biological Entity ◽  
Sperm Cells ◽  
Soft Magnetic ◽  
Actuation Frequency ◽  
Magnetic Microrobots

We develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug delivery. We present a single-step electrostatic self-assembly technique to fabricate IRONSperms, soft magnetic microswimmers that emulate the motion of motile sperm cells. Our experiments and theoretical predictions show that the swimming speed of IRONSperms exceeds 0.2 body length/s (6.8 ± 4.1 µm/s) at an actuation frequency of 8 Hz and precision angle of 45°. We demonstrate that the nanoparticle coating increases the acoustic impedance of the sperm cells and enables localization of clusters of IRONSperm using ultrasound feedback. We also confirm the biocompatibility and drug loading ability of these microrobots, and their promise as biocompatible, controllable, and detectable biohybrid tools for in vivo targeted therapy.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

scholarly journals Dual Targeting of Cancer Cells and MMPs with Self-Assembly Hybrid Nanoparticles for Combination Therapy in Combating Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1990
Author(s):  
Kai Zhang ◽  
Jingjing Li ◽  
Xiaofei Xin ◽  
Xiaoqing Du ◽  
Di Zhao ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Cells ◽  
Self Assembly ◽  
Chemotherapeutic Agents ◽  
Hybrid Nanoparticles ◽  
Control Group ◽  
Hyperthermia Treatment ◽  
Immune Modulators ◽  
Dual Targeting

The co-delivery of chemotherapeutic agents and immune modulators to their targets remains to be a great challenge for nanocarriers. Here, we developed a hybrid thermosensitive nanoparticle (TMNP) which could co-deliver paclitaxel-loaded transferrin (PTX@TF) and marimastat-loaded thermosensitive liposomes (MMST/LTSLs) for the dual targeting of cancer cells and the microenvironment. TMNPs could rapidly release the two payloads triggered by the hyperthermia treatment at the site of tumor. The released PTX@TF entered cancer cells via transferrin-receptor-mediated endocytosis and inhibited the survival of tumor cells. MMST was intelligently employed as an immunomodulator to improve immunotherapy by inhibiting matrix metalloproteinases to reduce chemokine degradation and recruit T cells. The TMNPs promoted the tumor infiltration of CD3+ T cells by 2-fold, including memory/effector CD8+ T cells (4.2-fold) and CD4+ (1.7-fold), but not regulatory T cells. Our in vivo anti-tumor experiment suggested that TMNPs possessed the highest tumor growth inhibitory rate (80.86%) compared with the control group. We demonstrated that the nanoplatform could effectively inhibit the growth of tumors and enhance T cell recruitment through the co-delivery of paclitaxel and marimastat, which could be a promising strategy for the combination of chemotherapy and immunotherapy for cancer treatment.

scholarly journals Trifluoromethionine, a Prodrug Designed against Methionine γ-Lyase-Containing Pathogens, Has Efficacy In Vitro and In Vivo against Trichomonas vaginalis

2001 ◽  
Vol 45 (6) ◽  
pp. 1743-1745 ◽  
Author(s):  
Graham H. Coombs ◽  
Jeremy C. Mottram
Keyword(s):  
Drug Target ◽  
Trichomonas Vaginalis ◽  
Anaerobic Bacteria ◽  
Protozoan Parasite ◽  
Chemotherapeutic Agents ◽  
Single Step ◽  
Lesion Formation ◽  
Highly Active

ABSTRACT Methionine γ-lyase, the enzyme which catalyzes the single-step conversion of methionine to α-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasiteTrichomonas vaginalis, to anaerobic bacteria containing methionine γ-lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.

A single-step multi-level supramolecular system for cancer sonotheranostics

2019 ◽  
Vol 4 (1) ◽  
pp. 190-195 ◽  
Author(s):  
Huirong Lin ◽  
Shuang Li ◽  
Junqing Wang ◽  
Chengchao Chu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Self Assembly ◽  
Single Step ◽  
Supramolecular System ◽  
Therapeutic Effects ◽  
Invasive Approach ◽  
Non Invasive ◽  
Ionic Crosslinking ◽  
Critical Issues ◽  
Multi Level

A multi-level supramolecular system produced by single-step Fe3+-mediated ionic crosslinking self-assembly can overcome the critical issues of current sonodynamic therapy (SDT) and address the need to monitor therapeutic effects in vivo with a non-invasive approach.

scholarly journals Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity

2020 ◽  
Vol 6 (45) ◽  
pp. eabc1725
Author(s):  
Yinxian Yang ◽  
Bingjun Sun ◽  
Shiyi Zuo ◽  
Ximu Li ◽  
Shuang Zhou ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Self Assembly ◽  
Rational Design ◽  
Colloidal Stability ◽  
Drug Loading ◽  
High Drug ◽  
Tumor Selectivity ◽  
Poor Stability ◽  
High Drug Loading

Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.

Physicochemical and Drug Delivery Aspects of Lipid-Based Liquid Crystalline Nanoparticles: A Case Study of Intravenously Administered Propofol

2006 ◽  
Vol 6 (9) ◽  
pp. 3017-3024 ◽  
Author(s):  
Markus Johnsson ◽  
Justas Barauskas ◽  
Andreas Norlin ◽  
Fredrik Tiberg
Keyword(s):  
Drug Delivery ◽  
Self Assembly ◽  
Liquid Crystalline ◽  
Drug Loading ◽  
Drug Substances ◽  
Physicochemical Features ◽  
Liquid Crystalline Nanoparticles ◽  
Effect Duration

Liquid crystalline nanoparticles (LCNP) formed through lipid self-assembly have a range of attractive properties as in vivo drug delivery carriers. In particular they offer: a wide solubilization spectrum, and consequently high drug payloads; effective encapsulation; stabilization and protection of sensitive drug substances. Here we present basic physicochemical features of non-lamellar LCNP systems with a focus on intravenous drug applications. This is exemplified by the formulation properties and in vivo behavior using the drug substance propofol; a well-known anesthetic agent currently used in clinical practice in the form of a stable emulsion. In order to appraise the drug delivery features of the LCNP system the current study was carried out with a marketed propofol emulsion product as reference. In this comparison the propofol-LCNP formulation shows several useful features including: higher drug-loading capacity, lower fat-load, excellent stability, modified pharmacokinetics, and an indication of increased effect duration.

scholarly journals Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma

Bioimpacts ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 241-252 ◽  
Author(s):  
Maryam Monajati ◽  
Shirin Tavakoli ◽  
gholam hossein yousefi ◽  
Samira Sadat Abolmaali ◽  
AliMohammad Tamaddon
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Spherical Shape ◽  
Chemotherapeutic Agents ◽  
Log P ◽  
Specific Cytotoxicity ◽  
The Impact

Introduction: Sorafenib (SFB) is an FDA-approved chemotherapeutic agent with a high partition coefficient (log P = 4.34) for monotherapy of hepatocellular carcinoma (HCC). The oral bioavailability is low and variable, so it was aimed to study the application of the polymeric nanoassembly of cholesterol conjugates of branched polyethyleneimine (PEI) for micellar solubilization of SFB and to investigate the impact of the polymer PEGylation on the physicochemical and cellular characteristics of the lipopolymeric dispersions. Methods: Successful synthesis of cholesterol-PEI lipopolymers, either native or PEGylated, was confirmed by FTIR, 1H-NMR, pyrene assay methods. The nanoassemblies were also characterized in terms of morphology, particle size distribution and zeta-potential by TEM and dynamic light scattering (DLS). The SFB loading was optimized using general factorial design. Finally, the effect of particle characteristics on cellular uptake and specific cytotoxicity was investigated by flow cytometry and MTT assay in HepG2 cells. Results: Transmission electron microscopy (TEM) showed that PEGylation of the lipopolymers reduces the size and changes the morphology of the nanoassembly from rod-like to spherical shape. However, PEGylation of the lipopolymer increased critical micelle concentration (CMC) and reduced the drug loading. Moreover, the particle shape changes from large rods to small spheres promoted the cellular uptake and SFB-related cytotoxicity. Conclusion: The combinatory effects of enhanced cellular uptake and reduced general cytotoxicity can present PEGylated PEI-cholesterol conjugates as a potential carrier for delivery of poorly soluble chemotherapeutic agents such as SFB in HCC that certainly requires further investigations in vitro and in vivo.

scholarly journals Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

Medicines ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. 87 ◽  
Author(s):  
Francesco Petrella ◽  
Isabella Rimoldi ◽  
Stefania Rizzo ◽  
Lorenzo Spaggiari
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Tumour Microenvironment ◽  
Chemotherapeutic Agents ◽  
Immunomodulatory Activity ◽  
Neoplastic Cells

Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

scholarly journals State-of-the-Art Irradiation Technology for Polymeric Hydrogel Fabrication and Application in Drug Release System

2021 ◽  
Vol 8 ◽  
Author(s):  
Muhammad Asim Raza ◽  
Jin-Oh Jeong ◽  
Sang Hyun Park
Keyword(s):  
Drug Release ◽  
Gamma Ray ◽  
Drug Loading ◽  
High Energy ◽  
Single Step ◽  
Antibiotic Drugs ◽  
Gamma Ray Irradiation ◽  
Polymeric Hydrogels

Chronic and debilitating diseases can be marginally cured by anti-inflammatory, antiseptic, and antibiotic drugs, there is still need for more efficacious delivery approaches. Biodegradable and biocompatible polymeric hydrogels are essential requirements for drug release systems due to sustained or targeted drug delivery. Irradiation crosslinking of polymers is considered a safe route for the fabrication of hydrogels because crosslinking takes place without addition of unnecessary toxic reagents such as initiators or crosslinkers. This technology is a useful way to induce sterilization and crosslinking in a single step. Several natural and synthetic polymers in different combinations are crosslinked through high energy ionizing radiation such as electron beam and gamma ray irradiation. Polymeric hydrogels prepared using these techniques exhibit good gel fraction, swelling ratio, and mechanical properties. In addition, hydrogels possess drug loading and release characteristics, antimicrobial characteristics, and in-vivo/in-vitro cytocompatibility. The advantage of biodegradable and biocompatible drug release systems is the controlled release of drugs without deleterious effects on targeted sites. This mini review about irradiation crosslinked hydrogels will provide sufficient guidelines for new researchers to proceed further in this field.

scholarly journals O-P05 Gemcitabine and paclitaxel loaded microbubbles for the treatment of pancreatic cancer

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Keiran Logan ◽  
John Callan
Keyword(s):  
Pancreatic Cancer ◽  
Drug Loading ◽  
Tumour Volume ◽  
Single Step ◽  
Promising Alternative ◽  
One Step ◽  
Transphosphatidylation Reaction ◽  
Subsequent Incorporation

Abstract Background Ultrasound targeted microbubble destruction (UTMD) has emerged as an effective strategy for the delivery of drug payloads to solid tumours. However, loading a single microbubble (MB) formulation with two drug payloads is challenging and often involves several manipulations post-MB preparation to enable attachment of drug payloads which can be cumbersome and generally results in low / inconsistent drug loading. Here we report a one-step synthesis of a gemcitabine-functionalised phospholipid and its subsequent incorporation into a stable MB formulation co-loaded with paclitaxel (PTX). The efficacy of the MB conjugate was determined in a Panc-1 spheroid model and ectopic BxPC-3 tumour model of pancreatic cancer. Methods Gemcitabine-modified phospholipid (Lipid-Gem MB) was prepared from 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC) though a transphosphatidylation reaction using gemcitabine (Gem) as the acceptor alcohol. Lipid-Gem MB and Lipid-Gem-PTX MB were prepared from Lipid-Gem MB and/or PTX using a standard thin-film hydration technique followed by sonication in the presence of PFB gas. In vitro efficacy of Lipid-Gem MB and Lipid-Gem-PTX MB were determined in Panc-1 spheroids using an MTT assay. The in vivo effectiveness was determined in BxPC-3 tumour bearing mice following IV administration of either Lipid-Gem MB or Lipid-Gem-PTX MB plus ultrasound (US). Free Gem, free Gem + PTX and untreated mice were used for comparative purposes. Results Spheroids treated with Lipid-Gem MB +US or Lipid-Gem-PTX MB +US were significantly reduced relative to spheroids treated with US alone (p = 0.033 and p = 0.0031 respectively) or with the respective MB formulation alone (i.e. no US) (p = 0.0336 and p = 0.0037 respectively). Furthermore, cell viability for spheroids treated with Lipid-Gem-PTX MB +US was significantly reduced compared with spheroids treated with Lipid-Gem MB +US (p = 0.0077) (Figure a). Mice treated with Lipid-Gem MB +US or Lipid-Gem-PTX MB +US showed an average change in tumour volume of + 7 ± 7% and -10 ± 10 % respectively compared with +45 ±10% and +30 ± 10% for free gem and free gem + PTX respectively (Figure b). Conclusions A Gem-modified lipid was succesfully synthesised using a single step reaction and was subsequently incorporated into MBs containging PTX, eliminating the need for cumbersome drug conjgation methods. UTMD mediated treatment of Panc-1 spheroids and BxPC-3 tumours demonstrated the efficacy and tolerability of the formulations. Given that all components of this formulation are already clinicaly apporved, UTMD using Lipid-Gem-PTX MB offers a promising alternative to existing treatments

Sign in / Sign up

Export Citation Format

Share Document