Organic Nanocarriers for Brain Drug Delivery
Carla Vitorino, Andreia Jorge, Alberto Pais in Nanoparticles for Brain Drug Delivery, 2021
Other advantages of liposomes, as potential ONCs for brain drug delivery, are related to their very adjustable properties which may change with size, preparation method and lipid composition, which also defines the type of charge and charge density of the liposomal surface [2, 65, 66]. In terms of brain delivery, it may be beneficial to include cationic lipids, such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammonium bromide (DODAB) or dioctadecyldimethylammonium chloride (DODAC), in the composition of the liposomes, rendering them with a positively charged surface. Cationic liposomes cross the BBB through the AMT mechanism [2, 14, 75, 76]. Moreover, cationic liposomes may also be used as transfection carriers to deliver genetic material into the cells, avoiding lysosomal digestion [77]. In this case, besides bearing cationic lipids, liposomes are also composed of neutral-charged helper lipids, like 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or monoolein, with fusogenic properties [77, 78]. These nucleic acid-loaded NCs, called lipoplexes, are formed by nucleic acid complexation and compaction, a process which initiates with electrostatic interaction between the cationic liposomal surface and anionic phosphate groups in nucleic acid material [77] (Fig. 4.4).
The Regulatory Process and Gene Therapy 1
Eric Wickstrom in Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Other modifications may consist of changes in lipids or other formulation components used with vectors. Different lipid components, different ratios of two lipids, or different ratios of lipid to DNA may be used to formulate a vector for administration to patients. The properties of the particular lipids used will affect the activity of liposomes in enhancing transfection (Feigner et al., 1994). Use of a new lipid requires safety information on that new lipid, but not necessarily in conjunction with the precise vector proposed for use if the new lipid has been used with other vectors. If tissue localization, germ line alteration, and classical animal pharmacology/toxicology data are compared for use of varied lipid ratios, compositions, or ratios to DNA, this data can be used to evaluate whether such studies are necessary for additional combinations.
Radio-Electro-Chemotherapy of Cancer: New Perspectives for Cancer Treatment
Pandit B. Vidyasagar, Sagar S. Jagtap, Omprakash Yemul in Radiation in Medicine and Biology, 2017
With the advancement in electronics, many companies are manufacturing electroporators of different specifications. Today, the most frequent application of electroporation is transfection of cells, involving the cellular uptake of DNA molecules. Also, this technology is used for the introduction of fluorescent probes into cells, electroloading of drugs, and transportation of molecules into the cells, etc. The applications have been extended to cancer research as well. This resulted in the emergence of a branch of therapeutics called electrochemotherapy (ECT), where the electric pulses are used to permeabilize the cell membrane and enhance the uptake of the molecules [34–35]. Electrochemotherapy is focused on three aspects: (i) electroporation of cells in living tissues, (ii) potentiation of cytotoxic drugs that are nonpermeant to cells, and (iii) intrinsic response of the body systems, i.e., immune response and blood flow patterns of the patient.
Advances in siRNA delivery in cancer therapy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Aishwarya Singh, Piyush Trivedi, Narendra Kumar Jain
Lipoplexes are one of the most attractive nonviral vectors for plasmid and siRNA delivery [31]. The transfection mechanism of liposomes involves static interactions between negatively charged nucleic acids and cationic lipids as shown in Figure 4(b). Once mixed along, they spontaneously form lipoplexes [32,33]. Cationic lipids (100–300 nm in size) can protect siRNA from enzymatic degradation and increase the circulating half-life and uptake by cells. Cationic lipids such as 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and N-{1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate (DOTMA), along with helper lipids such as DOPE, are often used to form cationic liposomes and complex with negatively charged deoxyribonucleic acid and siRNA, resulting in high in vitro transfection efficiency [34]. Commercially available formulations like lipofectamine 2000 are used for in vitro transfection [35]. Cationic liposomes have limited success in vivo, they show dose-dependent toxicity and pulmonary inflammation can arise as a result of reactive oxygen intermediates [36–38]. In a recent study, chemotherapeutics and MCL1-specific siRNA co-delivered using trilysine-derived cationic lipid-based liposomes was found to decrease the expression of MCL1 in the tumour tissues of keratin-forming human epidermal carcinoma (KB) cell-xenografted mice [39]. In one study of anticancer siRNA was co-formulated with a diagnostic agent in cationic liposomes for theranostic purposes [40].
Negatively charged phospholipids doped liposome delivery system for mRNA with high transfection efficiency and low cytotoxicity
Published in Drug Delivery, 2023
Lin Wang, Huanchun Xing, Shuai Guo, Wenbin Cao, Zinan Zhang, Lijuan Huang, Sui Xin, Yuan Luo, Yongan Wang, Jun Yang
Further clarification was needed regarding whether the absolute amount or the proportion of positive charges played a more important role in transfection efficiency. A series of liposomes composed of cationic lipids (DOTAP) with a fixed mass and anionic lipids (POPS) of different masses were designed and synthesized by mixing method. After transfection of cells for 24 h, fluorescent images of EGFP showed that liposome (DOTAP 0.1328 mg/mL, POPS 0 mg/mL, 7:0 molar ratio) could effectively transfect mRNA into proteins (Figure 4(A) i, (B)). When the cationic lipids content in the system remained unchanged, the liposome transfection efficiency gradually decreased with an increase amount of anionic lipids (Figure 4(A) ii, DOTAP 0.1328 mg/mL, POPS 0.0638 mg/mL, 7:3 molar ratio). The liposomes completely lost the ability to transfect mRNA when the increased anionic lipids shielded most of the positively charged material (7:7 and 7:14 molar ratio, Figure 4(A) iii, iv and (C)). These results suggested that the key point of transfection efficiency of the liposome was the proportion of the core cationic lipids in the whole liposome system, but not its dosage.
Efficacy of siRNA-loaded nanoparticles in the treatment of K-RAS mutant lung cancer in vitro
Published in Journal of Microencapsulation, 2022
Ayse Gencer, Ipek Baysal, Emirhan Nemutlu, Samiye Yabanoglu-Ciftci, Betul Arica
Nanotechnological drug delivery systems, as a nonviral gene transfection method, have been studied and considered highly promising in recent years. Nanotechnological gene delivery systems can provide the transfection of siRNA into cells while eliminating its stability problems. Liposomes, polymeric nanoparticles, solid lipid nanoparticles, inorganic nanoparticles, dendrimers and nanocrystals can be used as a nonviral gene transfection method (Choi et al.2014, Chen et al.2016, Gencer et al.2021). Polymeric nanoparticles have some advantages over the other drug delivery systems such as having much higher stability in biological fluids, thus increasing the stability of the active substance it carries and staying in circulation for a long time, being biocompatible and biodegradable, relatively easy production techniques, being able to be produced inhomogeneous shape and size, high drug loading capacity (Masood 2016, Kumar 2007). Polylactic acid (PLA) (Perez et al.2001), poly (lactic acid-co-glycolic acid) (PLGA) (Harguindey et al.2017), polyethyleneimine (PEI) (Kichler et al.2001), poly(L-lysine) (PLL) (Askarian et al.2015), chitosan (Ragelle et al.2014), and polyalkylcyanoacrylate (PACA) (Duan et al.2009) have been used successfully to prepare polymeric nanoparticles as a gene delivery system.
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