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Cationic Lipid-Based Gene Delivery: An Update
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
In summary, three major potential problems seem to limit the overall transfection efficiency of cationic liposomes. First, all of the reported electron microscopy studies have revealed a low frequency of DNA-lipid complex escaping from the endosomal compartment, and have shown that most of the particles are transported to lysosomes and degraded. Further development of DNA delivery systems aimed at increasing endosomal release of DNA-lipid complexes should be an interesting direction for research related to cationic liposome-mediated gene transfer. Another important issue is how to minimize the inhibitory effect of serum or other biological fluids. There are some initial observations indicating that certain chemical properties of cationic lipids (20) and certain DNA-lipid formulations (28) could render the system resistant to serum inhibition. Hopefully, more basic studies will help to elucidate the mechanisms of serum resistance and will provide a rationale for synthesis of new lipids or improved formulations. The third issue is a safety issue. Although cationic liposomes have been tested and proven to be safe for humans in relatively small doses, toxicity of doses likely to be required for clinical uses has not been thoroughly tested. Recently reported animal studies indicate that toxicity ranging from mild inflammation to death can occur with certain cationic liposome formulations (11,12) at high doses (11). Careful pharmacology and toxicology studies are needed to find the precise causes of toxicity so that cationic liposome-mediated gene delivery technology suitable for use in humans can be developed.
Liposomes
Published in Danilo D. Lasic, LIPOSOMES in GENE DELIVERY, 2019
A number of studies address the colloidal stability of charged liposomes. Similar behavior of anionic and cationic liposome stability was observed. Later, other forces were introduced to explain instability of small vesicles as compared with large ones. Namely, it was claimed that small DODAC vesicles contain hydrophobic defects that could cause precipitation. Although this explanation seems plausible, in line with recent cryoelectron microscopy observations and previously reported studies that claimed there is a coexistence of open fragments in DODAC systems (Pansu et al., 1990), further work on better-defined systems will be required to assess these issues. We shall use some of the above concepts to explain the stability of genosomes.
Gene Therapy
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Seiji B. Shibata, Scott M. Graham
A 20% correction of nasal potential in nine patients, peaking at three days and disappearing by seven days, was reported by Caplen et al. 60 employing a cationic liposome vector. The vector was applied by a nasal pump spray, a practical method for likely repeat administration should clinical gene therapy become a reality. In 1997, Gill et al. 61 showed functional CFTR gene transfer in six of eight subjects in a further nasal mucosal/liposome study. Alton et al. 62 reported a placebo-controlled study of liposome-mediated CFTR transfer to the lungs and nasal mucosa of CF patients. The treatment group displayed some improvement in airway potential not seen in the liposome-only group. Interestingly, some aspects of toxicity were only seen with pulmonary administration leading the authors to question the value of the nasal model, at least from a safety viewpoint.
Systematic review on activity of liposomal encapsulated antioxidant, antibiotics, and antiviral agents
Published in Journal of Liposome Research, 2022
Reshna K. R, Preetha Balakrishnan, Sreerag Gopi
Cationic liposomes contain positively charged lipids. It is widely used for the gene therapy due to the interaction with negatively charged DNA. In cationic lipid, the core component of liposome contain positively charged head group and one or two hydrophobic tail regions made by hydrocarbon chain or steroid structure (Figure 3(b)) (Daraee et al.2016, Shim et al.n.d.). Frequently, cationic liposomes are comprised a cationic lipid and a neutrally charged lipid. Catalytic lipids are a class of amphiphiles with positive charges that bind with negatively charged DNA to form complexes containing condensed DNA (Simões et al.2005). Cationic liposome is one of the most commonly used nonviral gene delivery vectors and it is widely used as a standard gene vector especially for in vitro transfection (Ozpolat et al.2014). The low toxicity, low immunogenicity, high loading capacity, and easy preparation contributed to the wide application of cationic liposomes. Immunoliposomes with neutral charge showed potential in delivery of various genes into brain, and the neutral charge provided the liposomes with long blood circulation time, which was superior to cationic liposomes (Yin et al.2016).
Cationic liposome decorated with cyclic RGD peptide for targeted delivery of anti-STAT3 siRNA to melanoma cancer cells
Published in Journal of Drug Targeting, 2022
Ehsan Khabazian, Faezeh Vakhshiteh, Parisa Norouzi, Yousef Fatahi, Rassoul Dinarvand, Fatemeh Atyabi
The development of siRNA-based medicines has gained more attention as compared to conventional therapeutic approaches for melanoma treatment. Melanoma is the most severe type of human skin cancer owing to its high metastatic ability into the organs such as brain, liver and lung as well as developed tumour resistance to conventional therapies [20]. siRNA can be a promising therapeutic strategy due to its potential to inhibit specific molecular pathways involved in tumour development and progression. However, efficient systemic administration of siRNA therapeutics is being restricted because of some barriers including enzymatic degradation of siRNA in blood circulation, rapid renal clearance, uptake by the RES, low cellular penetration due to the high hydrophilicity and molecular weight of siRNA [21]. Consequently, fabrication of an effective and safe vector for systemic delivery of siRNA remained as a critical topic. The present study aims to develop an effective and targeted delivery system that can precisely deliver siRNA against STAT3 transcription factor into the B16F10 murine melanoma cancer cells. For the purpose, a cationic liposome as a lipid-based gene delivery system owing to its desirable properties such as biocompatibility, biodegradability and facile formation was developed. Cationic liposomes can electrostatically complex with negatively charged siRNA and form lipoplexes, which can provide high transfection efficiency by interacting with negatively charged cell membranes and protect siRNA from degradation by serum nucleases [22,23].
Development of thermostable vaccine adjuvants
Published in Expert Review of Vaccines, 2021
Dehydration of liposomes without stabilizing excipients can cause physical damages including vesicle fusion, leakage, aggregation, and phase separation [88]. A variety of excipients have been utilized to stabilize liposomal formulations during drying processes, including sugars, sugar alcohols, polyols, polymers, amino acids, and polypeptides [89]. Similar to the stabilizing mechanisms discussed for emulsions, these excipients stabilize liposomes through one or both of the following mechanisms: (1) vitrification into an amorphous glass matrix that reduces molecular mobility and serves as a physical barrier between adjacent liposomal bilayers and (2) replacement of hydrogen bonds formerly supplied by water via direct interaction with the lipid polar head groups [89,90]. Disaccharides are among the most commonly used excipients to protect liposomal vaccine formulations during lyophilization [91–93]. A cationic liposome mixed with a model antigen and lyophilized in the presence of trehalose maintained its physicochemical characteristics as well as antigen adsorption and integrity after storage at 20°C for 12 weeks [92]. Another liposomal system containing a synthetic variant of the TLR4 agonist monophosphoryl lipid A (MPL) and the malaria vaccine antigen Pfs25 was lyophilized using sucrose and trehalose as excipients. Lyophilized Pfs25-bound liposomes maintained physicochemical stability and induced functional antibodies in mice following storage at 60°C for at least 6 weeks [93].