目次: :: Library Catalog

保存先:

書誌詳細
主要な著者:	Martínez Saraóz, Jessica Victoria, Chapa González, Christian
フォーマット:	Recurso digital
言語:
出版事項:	Zenodo 2021
主題:	Nanomedicine Lipid nanoparticles Nanoparticles Gene delivery Gene therapy Eye diseases Drug delivery Encapsulation efficiency Biomedical engineering
オンライン･アクセス:	https://doi.org/10.5281/zenodo.4741321
タグ:	タグ追加タグなし, このレコードへの初めてのタグを付けませんか!

目次:

<ul> <li>Introduction</li> </ul> Gene therapy is still beginning, and most human clinical trials are still in investigative states. Non-viral systems based on lipid nanoparticles have begun to show encouraging results, especially in ocular therapy. Lipid nanoparticles (LNP) represent a very promising strategy that could contribute to the clinical development of this therapy [1]. LNPs, including solid lipid nanoparticles and nanostructured lipid carriers, emerged in the 1990s as an alternative drug delivery system to liposomes and polymeric nanoparticles. The application of LNPs for the administration of ocular drugs dates back to 2002, when studies were carried out on solid lipid nanoparticles loaded with tobramycin [2]. Some of the advantages of the use of said nanoparticles are the use of physiologically acceptable lipids for their preparation, the possibility of avoiding the use of organic solvents in their preparation and a wide spectrum of use, since they are used for administration on the skin. , orally and intravenously. However, it also has some disadvantages, such as particle growth during storage, a tendency towards unpredictable gelation, unexpected changes in its polymorphic transitions, and its inherently low drug incorporation capacity due to the crystalline structure of the solid lipid. [3]. Despite the disadvantages that may arise, over the years LNPs have been characterized and implemented in the ocular area, such is the case of the multifunctional gene delivery system based on ECO ((1-aminoethyl) iminobis [N- (oleylcysteinyl-1-amino-ethyl) propionamide]) of lipids. In 2017 this delivery system demonstrated excellent gene transfection efficiency due to its unique ability to escape from the endosome. Modified fully trans-retinylamine pH-sensitive ECO / pDNA nanoparticles comprise a promising non-viral platform for the safe, efficient, and targeted delivery of gene therapies to treat retinal pigmented epithelial tissue-specific monogenic eye diseases [4]. Likewise, in 2019, in the search for an alternative treatment for retinoblastoma, cationic pH-sensitive LNPs were used to jointly administer miR-181a and melphalan for this disease. In this way, it was shown that the encapsulation of melphalan in liposomes drastically improved its efficiency, together with the addition of miR-181a, showing the ability of LNPs to deliver substances to the eye [5]. In the same year, 2019, the non-viral delivery of RNA therapies for various types of cells within the retina can be highlighted, which can provide new transformative approaches to prevent blindness. Some studies have emphasized that LNPs containing ionizable lipids with low pKa and unsaturated hydrocarbon chains showed the highest percentage of gene transfection in the eye after subretinal injection [6]. One of the most recent advances is the demonstration that Prosilic®, a non-viral vector delivery system of hybrid lipid and silicone nanoparticles, composed of biodegradable silicon nanoparticles (SiNP), lipids and amino acids, is capable of forming complex with siRNA and deliver it to the cornea after non-invasive topical administration. Because the delivery system is biodegradable and bioavailable, it has the ability to bind siRNA in high concentrations and deliver the cargo to cells both in vitro and in vivo [7]. LNPs have demonstrated the ability to improve the bioavailability of anti-infective, anti-inflammatory, anti-glaucoma agents or genetic material, which are administered through eye drops. Several characteristics of the LNP composition are of utmost importance to achieve efficient ocular therapy, such as good ocular tolerance, good physical stability, pharmacological protection, controlled drug release, good biocompatibility, specific targeting, the non-use of organic solvents. and the possibility of expansion. [8]. One of the most important aspects is pharmacological protection, which leads to efficient encapsulation of the gene [9]. Due to this, it is sought to find the size of the nanoparticle that helps to have a higher percentage encapsulation to later release the gene in the specific location and thus achieve a successful ocular therapy. <ul> <li>Research Question</li> </ul> What size lipid nanoparticle has the highest encapsulation efficiency based on the type of gene? This review covers gene delivery in ocular therapy, employing various LNP systems. Due to this it is necessary to establish the criteria shown below: <ul> <li>Inclusion criteria</li> </ul> • Articles containing recent information, covering the years 2015 to 2021. • The article must be related to an eye disease, lipid nanoparticles and gene therapy. • Indicates encapsulation efficiency in ocular therapy. • Indicates the size of the lipid nanoparticle and the characterization method. • Indicates the type of gene that is encapsulated in the lipid nanoparticle. • The articles are for research. • Experimental in vitro or in vivo studies between the ocular cell and the lipid nanoparticle. <ul> <li>Exclusion criteria</li> </ul> • Articles from before 2015. • Articles that are not written in the English language. • Articles that do not focus on diseases other than eye diseases. • Review, conference or comment articles. • Does not specify nanoparticle size or encapsulation efficiency. • Articles that cannot be fully accessed.   <ul> <li>General objective</li> </ul> • To determine the lipid nanoparticle that presents a higher percentage of encapsulation in the treatment of ocular diseases. <ul> <li>Specific objectives</li> </ul> • To identify what type of gene is encapsulated within the lipid nanoparticle. • To recognize the nanoparticle size with the highest encapsulation efficiency of the gene from each clinical or laboratory test. • To specify in which type of ocular cells the nanoparticles are introduced. • To determine which nanoparticle formulation has the highest encapsulation efficiency. <ul> <li>Justification for the study</li> </ul> Nanotechnology, and especially lipid nanoparticles, can improve the therapeutic efficacy, compliance and safety of ocular drugs, administered by different routes. Over the years, lipid nanoparticles have proven to be efficient as alternative delivery systems [9]. Thus, research to determine the nanoparticle size that better encapsulates the gene for eye diseases is of utmost importance, since through these results it is possible to know what would be the best characteristics of said LNP for future applications in the eye therapy. It should be noted that in 2019, the World Health Organization reported that Worldwide, at least 2.2 billion people have visual impairment, blindness, or an ophthalmological disease [10]. In this way, we can observe the importance of carrying out this research to find out more about what the possible optimal characteristics could be for the development of lipid nanoparticles for the treatment of these diseases. <ul> <li>Proposed methodology</li> </ul> 1. Performing a search in three databases, Web of Science, ScienceDirect and PubMed; as well as, information obtained from ClincialTrials will also be taken into account. 2. Use of the following keywords and booleans to find the bibliography on the subject: ("lipid nanoparticles" OR liposome) AND (Gene) AND (clinical OR therapy) AND (Ocular OR Eye) 3. Selection of all the articles obtained from the databases by means of the aforementioned search. 4. Purification of the documents obtained according to the inclusion and exclusion criteria by means of a prism flow diagram. 5. Data collection. 6. Preparation of a table to classify the size, type of gene, formulation of the LNP, ocular disease, type of cells in which the gene transfection will be carried out and the encapsulation efficiency obtained from the selected literature. 7. Preparation of a review that contains a detailed investigation and comparing these results in order to determine which is the best size that allows a better encapsulation of the gene.

類似資料