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Pharmaceuticals
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Lipid-Nanoparticle-Mediated Delivery of Small-Molecule and Nucleic Acid-Based Therapeutics
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Lipid-Nanoparticle-Mediated Delivery of Small-Molecule and Nucleic Acid-Based Therapeutics

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 5363

Special Issue Editor

Dr. Okhil Kumar Nag

E-Mail Website
Guest Editor
US Naval Research Laboratory, Center for Bio/Molecular Sci.& Eng. Bldg. 30, Code 6920 Office Room# 109, 4555 Overlook Avenue - SW, Washington, DC 20375, USA
Interests: nanoparticle to mammalian cells; controlling cellular functions; modulating and imaging neural activity; photophysical interactions of dyes; nanoparticles; liposomes; lipid nanoparticles; nanoparticle-mediated drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipid nanoparticles (LNPs) have generated tremendous interest in the field of pharmaceutical research as promising vehicles to deliver a variety of therapeutics, including small molecules and nucleic-acid-based medicine. Recently, LNP-based formulations of therapeutics are especially applied to transporting and effectively delivering mRNA vaccines to the cells. LNPs play critical roles in effectively stabilizing, protecting, transporting, and delivering these medicines to cells/tissues. In addition to the tunable size of LNPs, their lipid composition, surface properties, stability, and targeting capacities are critical parameters that need to be controlled and optimized for specific therapeutic needs for the treatment. This Special Issue of Pharmaceuticals focuses on new strategies and advances in LNP-based formulations of therapeutics using various forms of LNPs, including nanostructured LNPs, solid LNPs, and liposomes. We invite researchers to publish their original research and review articles with expert opinions and perspectives in the aforementioned areas.

Dr. Okhil Kumar Nag
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (2 papers)

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Research

12 pages, 2878 KiB  
Article
Fusogenic Liposomes for the Intracellular Delivery of Phosphocreatine
by Okhil K. Nag, Eunkeu Oh and James B. Delehanty
Pharmaceuticals 2024, 17(10), 1351; https://doi.org/10.3390/ph17101351 - 10 Oct 2024
Cited by 2 | Viewed by 1926
Abstract
Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine [...] Read more.
Background/Objective: Maintaining intracellular adenosine triphosphate (ATP) levels is essential for numerous cellular functions, including energy metabolism, muscle contraction, and nerve impulse transmission. ATP is primarily synthesized in mitochondria through oxidative phosphorylation. It is also generated in the cytosol under anaerobic conditions using phosphocreatine (PCr) as a phosphate donor to adenosine diphosphate. However, the intracellular delivery of exogenous PCr is challenging as it does not readily cross the plasma membrane. This complicates the use of PCr as a therapeutic agent to maintain energy homeostasis or to treat conditions like cerebral creatine deficiency syndrome (CDS), which results from defective creatine transporters. Methods: This study employs the use of fusogenic liposomes to deliver PCr directly into the cytosol, bypassing membrane impermeability issues. We engineered various 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based fusogenic liposomes, incorporating phospholipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in combination with phospholipid-aromatic dye components to facilitate membrane fusion and to enhance the delivery of the PCr cargo. Liposomal formulations were co-loaded with membrane-impermeable chromophores and PCr and studied on live cells using confocal microscopy. Conclusions: We demonstrated the successful intracellular delivery of these agents and observed a 23% increase in intracellular ATP levels in cells treated with PCr-loaded liposomes. This increase was not observed with free PCr, confirming the effectiveness of the liposome-based delivery system. Additionally, cell viability assays showed minimal toxicity from the liposomes. Our results indicate that fusogenic liposomes are a promising method for the delivery of PCr (and potentially other cell-impermeable therapeutic agents) to the cellular cytosol. The approach demonstrated here could be advantageous for treating energy-related disorders and improving cellular energy homeostasis. Full article
(This article belongs to the Special Issue Lipid-Nanoparticle-Mediated Delivery of Small-Molecule and Nucleic Acid-Based Therapeutics)
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26 pages, 7586 KiB  
Article
Comparative Analysis of the Physicochemical and Biological Characteristics of Freeze-Dried PEGylated Cationic Solid Lipid Nanoparticles
by David A. Narváez-Narváez, María Duarte-Ruiz, Sandra Jiménez-Lozano, Cristina Moreno-Castro, Ronny Vargas, Anna Nardi-Ricart, Encarna García-Montoya, Pilar Pérez-Lozano, Josep Mª Suñé-Negre, Cristina Hernández-Munain, Carlos Suñé and Marc Suñé-Pou
Pharmaceuticals 2023, 16(11), 1583; https://doi.org/10.3390/ph16111583 - 9 Nov 2023
Cited by 4 | Viewed by 2365
Abstract
Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were [...] Read more.
Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (~170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30–35 mV. Notably, Gelucire again produced the smallest particle size (211.1 ± 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (~235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity. Full article
(This article belongs to the Special Issue Lipid-Nanoparticle-Mediated Delivery of Small-Molecule and Nucleic Acid-Based Therapeutics)
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