scholarly journals Role of cationic lipids for the formulation of lipoplexes

Author(s):  
Varsha Singh ◽  
Pramod Kumar Sharma ◽  
Md. Aftab Alam

Cationic lipids are widely used for their advantages over viral gene transfer as they are non-immunogenic and their production is easy. The formation of cationic liposomes to lipoplexes with the help of cationic lipids has been done. Cationic lipids are often used in combination with helper lipids such as DOPE or cholesterol for defining their structural properties. The mode of lipoplex formation has been described in this review. This review also focuses on the parameters that affects the physico-chemical properties of lipoplexes describing their use for the cationic lipid based on the gene therapy purposes. The current status and various prospects for the transfection efficacy of lipoplexes is also been described.

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 25
Author(s):  
Tony Le Le Gall ◽  
Mathieu Berchel ◽  
Lee Davies ◽  
Angélique Mottais ◽  
Rosy Ghanem ◽  
...  

Aerosol lung gene therapy using non-viral delivery systems represents a credible therapeutic strategy for chronic respiratory diseases, such as cystic fibrosis (CF). Progress in CF clinical setting using the lipidic formulation GL67A has demonstrated the relevance of such a strategy while emphasizing the need for more potent gene transfer agents. In recent years, many novel non-viral gene delivery vehicles were proposed as potential alternatives to GL67 cationic lipid. However, they were usually evaluated using procedures difficult or even impossible to implement in clinical practice. In this study, a clinically-relevant administration protocol via aerosol in murine lungs was used to conduct a comparative study with GL67A. Diverse lipidic compounds were used to prepare a series of formulations inspired by the composition of GL67A. While some of these formulations were ineffective at transfecting murine lungs, others demonstrated modest-to-very-efficient activities and a series of structure-activity relationships were unveiled. Lipidic aminoglycoside derivative-based formulations were found to be at least as efficient as GL67A following aerosol delivery of a luciferase-encoding plasmid DNA. A single aerosol treatment with one such formulation was found to mediate long-term lung transgene expression, exceeding half the animal’s lifetime. This study clearly supports the potential of aminoglycoside-based cationic lipids as potent GL67-alternative scaffolds for further enhanced aerosol non-viral lung gene therapy for diseases such as CF.


2021 ◽  
Vol 31 (1) ◽  
Author(s):  
Thomas Thiebault ◽  
Laëtitia Fougère ◽  
Anaëlle Simonneau ◽  
Emilie Destandau ◽  
Claude Le Milbeau ◽  
...  

AbstractThis study investigated the potential of sediments accumulated in sewer systems to record human activities through the occurrence of drug target residues (DTR). The installation studied is 17 m deep underground decantation tank that traps the coarse fractions of a unitary sewer system (northern part of Orléans, France), collecting both stormwater and wastewater. The sediments deposited in this tank could constitute a nonesuch opportunity to study the historical evolution of illicit and licit drug consumption in the catchment, however, the deposition processes and the record of DTRs remain largely unknown at present. Five cores were acquired from 2015 to 2017. One hundred fifty-two sediment samples were extracted using a mixture of ultra-pure water:methanol (1:1) prior to analysis of the extracts by high-pressure liquid chromatography coupled to tandem mass spectrometry. Several classical sedimentological analyses such as total organic carbon, facies description and granulometry were also performed on these samples, in order to understand the most important factors (e.g., physico-chemical properties of the DTRs, solid type, assumed load in wastewater) impacting their deposition.The key role of the speciation of DTRs was highlighted by the higher contents in neutral and anionic DTRs in organic layers, whereas only cationic DTRs were found in mineral layers. The considerable modifications in the sediments’ properties, generated by distinct origins (i.e., stormwater or wastewater), are therefore the most important drivers that must be taken into account when back-calculating the historical patterns of drug consumption from their DTR concentrations in decantation tank sediments. Further research remains necessary to fully understand the deposition process, but this study provides new clues explaining these temporal evolutions.


Nanomaterials ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 9 ◽  
Author(s):  
Artiom Skripka ◽  
Dominyka Dapkute ◽  
Jurga Valanciunaite ◽  
Vitalijus Karabanovas ◽  
Ricardas Rotomskis

Nanomaterials have permeated various fields of scientific research, including that of biomedicine, as alternatives for disease diagnosis and therapy. Among different structures, quantum dots (QDs) have distinctive physico-chemical properties sought after in cancer research and eradication. Within the context of cancer therapy, QDs serve the role of transporters and energy donors to photodynamic therapy (PDT) drugs, extending the applicability and efficiency of classic PDT. In contrast to conventional PDT agents, QDs’ surface can be designed to promote cellular targeting and internalization, while their spectral properties enable better light harvesting and deep-tissue use. Here, we investigate the possibility of complex formation between different amphiphilic coating bearing QDs and photosensitizer chlorin e6 (Ce6). We show that complex formation dynamics are dependent on the type of coating—phospholipids or amphiphilic polymers—as well as on the surface charge of QDs. Förster’s resonant energy transfer occurred in every complex studied, confirming the possibility of indirect Ce6 excitation. Nonetheless, in vitro PDT activity was restricted only to negative charge bearing QD-Ce6 complexes, correlating with better accumulation in cancer cells. Overall, these findings help to better design such and similar complexes, as gained insights can be straightforwardly translated to other types of nanostructures—expanding the palette of possible therapeutic agents for cancer therapy.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1645
Author(s):  
Bart De Geest ◽  
Mudit Mishra

Under physiological circumstances, there is an exquisite balance between reactive oxygen species (ROS) production and ROS degradation, resulting in low steady-state ROS levels. ROS participate in normal cellular function and in cellular homeostasis. Oxidative stress is the state of a transient or a persistent increase of steady-state ROS levels leading to disturbed signaling pathways and oxidative modification of cellular constituents. It is a key pathophysiological player in pathological hypertrophy, pathological remodeling, and the development and progression of heart failure. The heart is the metabolically most active organ and is characterized by the highest content of mitochondria of any tissue. Mitochondria are the main source of ROS in the myocardium. The causal role of oxidative stress in heart failure is highlighted by gene transfer studies of three primary antioxidant enzymes, thioredoxin, and heme oxygenase-1, and is further supported by gene therapy studies directed at correcting oxidative stress linked to metabolic risk factors. Moreover, gene transfer studies have demonstrated that redox-sensitive microRNAs constitute potential therapeutic targets for the treatment of heart failure. In conclusion, gene therapy studies have provided strong corroborative evidence for a key role of oxidative stress in pathological remodeling and in the development of heart failure.


Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2866 ◽  
Author(s):  
Aniket Wahane ◽  
Akaash Waghmode ◽  
Alexander Kapphahn ◽  
Karishma Dhuri ◽  
Anisha Gupta ◽  
...  

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.


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