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Nanomaterials
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Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles
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Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (10 October 2021) | Viewed by 22030

Special Issue Editor

Dr. Angelina Angelova

E-Mail Website
Guest Editor
CNRS UMR 8612 "Institut Galien Paris-Saclay", Paris-Saclay University, F-91400 Orsay, France
Interests: lipid/protein nanoassemblies; liquid crystalline phases; cubosomes; self-assembled nanostructures and nanoparticles with neuroprotective properties; nanomedicine; nanocarriers for macromolecular drug delivery; membrane receptor nanoscale organization; lipids; peptides; proteins; BDNF; cyclodextrin; soft nanomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipid-based nanomaterials and nanoparticles are gaining increasing interest in targeted drug delivery, diagnostic imaging, and nanomedicine. They offer possibilities for encapsulation of both hydrophilic and hydrophobic bioactive guest molecules in nanoscale reservoirs for controlled multidrug release. Moreover, they represent safe systems for nanoformulation of protein and peptide drugs and nonviral delivery of gene-editing complexes. Considerable progress has been achieved with lipid membrane mimetic cubosome and spongosome nanoparticles for anticancer and transcutaneous applications, regeneration after spinal cord injury, and modulation of neural stem cells in brain repair. Recent strategies also include the embedding of drug-loaded lipid nanoparticles in hydrogel matrices and the fabrication of biocompatible scaffolds for neural tissue engineering and neuronal regeneration.

This Special Issue of Nanomaterials will focus on recent advances and ongoing cutting-edge research in liquid crystalline nanocarriers (cubosomes, spongosomes, hexosomes, and liposomes), nanostructured lipid carriers, solid lipid nanoparticles, and lipid–drug conjugates. The uses of lipid-based nanomaterials as multidrug sustained delivery systems and their potential therapeutic value in regenerative nanomedicine, treatment of neurodegenerative disorders, neuro- and cardioprotection, growth factor delivery strategies, reduction of neuroinflammation, topical delivery of antimicrobial peptides, and anticancer agents will be highlighted. The preclinical and clinical status and the future prospects for lipid nanoparticle uses in brain targeting, parenteral, topical, and oral delivery as well as in diagnostic and imaging applications will be considered. Remarkable attention will be given to the role of nanoparticle architectures and surface modifications in their cellular uptake mechanism.

Dr. Angelina Angelova
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. Nanomaterials is an international peer-reviewed open access semimonthly 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.

Keywords

  • lipid nanoparticles
  • liquid crystalline nanoassemblies
  • nanostructured lipid carriers
  • vesicles
  • protein drugs
  • peptide drugs
  • controlled dual-drug release
  • CRISPR-Cas9 delivery
  • nonviral gene delivery
  • antioxidant delivery
  • drug–lipid conjugates
  • neuroregeneration
  • cardioprotection
  • antitumor lipid-based nanoparticles
  • lipids in therapy

Published Papers (5 papers)

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Research

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20 pages, 3203 KiB  
Article
Tetrahydrocurcumin Lipid Nanoparticle Based Gel Promotes Penetration into Deeper Skin Layers and Alleviates Atopic Dermatitis in 2,4-Dinitrochlorobenzene (DNCB) Mouse Model
by Komal Saini, Nancy Modgill, Kamalinder K. Singh and Vandita Kakkar
Nanomaterials 2022, 12(4), 636; https://doi.org/10.3390/nano12040636 - 14 Feb 2022
Cited by 18 | Viewed by 2877
Abstract
Treatment of atopic dermatitis (AD) is challenging due to its complex pathophysiology. Tetrahydrocurcumin (THC) a polyphenolic, colorless compound that is more polar than curcumin. It possesses superior anti-inflammatory properties and has a clinical advantage over curcumin. The present study investigated the therapeutic effectiveness [...] Read more.
Treatment of atopic dermatitis (AD) is challenging due to its complex pathophysiology. Tetrahydrocurcumin (THC) a polyphenolic, colorless compound that is more polar than curcumin. It possesses superior anti-inflammatory properties and has a clinical advantage over curcumin. The present study investigated the therapeutic effectiveness of THC solid lipid nanoparticle (THC-SLN)-based gels in AD. THC-SLNs prepared using microemulsification resulted in a particle size of 109.2 nm as determined by nanoparticle tracking, and FTIR confirmed the entrapment of drug within the lipid matrix. THC-SLNs greatly enhanced skin hydration when tested both ex vivo and in vivo in Lacca mice. Deeper skin penetration was clearly established using dermatokinetics and CLSM. The in vivo pharmacodynamics of THC-SLNs gel in 2,4-dinitrochlorobenzene (DNCB)-induced AD mice showed enhanced bioactivity; reduced levels of TNF-α and IL-6; and complete healing, as evident from histopathological studies. Thus, the novel topical THC-SLN gel has potential to emerge as a safe alternative to conventional corticosteroids for AD and other skin disorders with overbearing inflammation. Full article
(This article belongs to the Special Issue Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles)
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19 pages, 5360 KiB  
Article
Advances in the Formulation and Assembly of Non-Cationic Lipid Nanoparticles for the Medical Application of Gene Therapeutics
by Richard K. Fisher III, Phillip C. West, Samuel I. Mattern-Schain, Michael D. Best, Stacy S. Kirkpatrick, Raymond A. Dieter III, Joshua D. Arnold, Michael R. Buckley, Michael M. McNally, Michael B. Freeman, Oscar H. Grandas and Deidra J. H. Mountain
Nanomaterials 2021, 11(3), 825; https://doi.org/10.3390/nano11030825 - 23 Mar 2021
Cited by 6 | Viewed by 3591
Abstract
Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) [...] Read more.
Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. PLPs can be modified with cell-penetrating peptides (CPPs) to enhance the intracellular delivery of liposomal cargo but encapsulate leakage upon CPP-PLP assembly is problematic. Here, we aimed to identify parameters that overcome these performance barriers by incorporating nucleic acid condensers during CPP-PLP assembly and screening variable ethanol injection parameters for optimization. CPP-PLPs were formed with R8-amphiphiles via pre-insertion, post-insertion and post-conjugation techniques and liposomes were characterized for size, surface charge, homogeneity, siRNA encapsulation efficiency and retention and cell associative properties. Herein we demonstrate that pre-insertion of stearylated R8 into PLPs is an efficient method to produce non-cationic CPP-PLPs and we provide additional assembly parameter specifications for a modified ethanol injection technique that is optimized for siRNA encapsulation/retention and enhanced cell association. This assembly technique could provide improved clinical translation of liposomal based gene therapy applications. Full article
(This article belongs to the Special Issue Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles)
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14 pages, 1498 KiB  
Article
Lipidic Cubic-Phase Nanoparticles (Cubosomes) Loaded with Doxorubicin and Labeled with 177Lu as a Potential Tool for Combined Chemo and Internal Radiotherapy for Cancers
by Adrianna Cytryniak, Ewa Nazaruk, Renata Bilewicz, Emilia Górzyńska, Kinga Żelechowska-Matysiak, Rafał Walczak, Adam Mames, Aleksander Bilewicz and Agnieszka Majkowska-Pilip
Nanomaterials 2020, 10(11), 2272; https://doi.org/10.3390/nano10112272 - 16 Nov 2020
Cited by 33 | Viewed by 3719
Abstract
Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (β−)-emitter, [...] Read more.
Lipid liquid-crystalline nanoparticles (cubosomes) were used for the first time as a dual-modality drug delivery system for internal radiotherapy combined with chemotherapy. Monoolein (GMO)-based cubosomes were prepared by loading the anticancer drug, doxorubicin and a commonly used radionuclide, low-energy beta (β−)-emitter, 177Lu. The radionuclide was complexed with a long chain derivative of DOTAGA (DOTAGA-OA). The DOTAGA headgroup of the chelator was exposed to the aqueous channels of the cubosomes, while, concerning OA, the hydrophobic tail was embedded in the nonpolar region of the lipid bilayer matrix, placing the radioactive dopant in a stable manner inside the cubosome. The cubosomes containing doxorubicin and the radionuclide complex increased the cytotoxicity measured by the viability of the treated HeLa cells compared with the effect of single-drug cubosomes containing either the DOX DOTAGA-OA or DOTAGA-OA-177Lu complex. Multifunctional lipidic nanoparticles encapsulating the chemotherapeutic agent together with appropriately complexed (β−) radionuclide are proposed as a potential strategy for effective local therapy of various cancers. Full article
(This article belongs to the Special Issue Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles)
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Review

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43 pages, 2412 KiB  
Review
Critical Review of Lipid-Based Nanoparticles as Carriers of Neuroprotective Drugs and Extracts
by Filipe Fernandes, Mónica Dias-Teixeira, Cristina Delerue-Matos and Clara Grosso
Nanomaterials 2021, 11(3), 563; https://doi.org/10.3390/nano11030563 - 24 Feb 2021
Cited by 25 | Viewed by 4903
Abstract
The biggest obstacle to the treatment of diseases that affect the central nervous system (CNS) is the passage of drugs across the blood-brain barrier (BBB), a physical barrier that regulates the entry of substances into the brain and ensures the homeostasis of the [...] Read more.
The biggest obstacle to the treatment of diseases that affect the central nervous system (CNS) is the passage of drugs across the blood-brain barrier (BBB), a physical barrier that regulates the entry of substances into the brain and ensures the homeostasis of the CNS. This review summarizes current research on lipid-based nanoparticles for the nanoencapsulation of neuroprotective compounds. A survey of studies on nanoemulsions (NEs), nanoliposomes/nanophytosomes and solid lipid nanoparticles (SLNs)/nanostructured lipid carriers (NLCs) was carried out and is discussed herein, with particular emphasis upon their unique characteristics, the most important parameters influencing the formulation of each one, and examples of neuroprotective compounds/extracts nanoencapsulated using these nanoparticles. Gastrointestinal absorption is also discussed, as it may pose some obstacles for the absorption of free and nanoencapsulated neuroprotective compounds into the bloodstream, consequently hampering drug concentration in the brain. The transport mechanisms through which compounds or nanoparticles may cross BBB into the brain parenchyma, and the potential to increase drug bioavailability, are also discussed. Additionally, factors contributing to BBB disruption and neurodegeneration are described. Finally, the advantages of, and obstacles to, conventional and unconventional routes of administration to deliver nanoencapsulated neuroprotective drugs to the brain are also discussed, taking into account the avoidance of first-pass metabolism, onset of action, ability to bypass the BBB and concentration of the drug in the brain. Full article
(This article belongs to the Special Issue Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles)
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22 pages, 4042 KiB  
Review
Advances in the Design of pH-Sensitive Cubosome Liquid Crystalline Nanocarriers for Drug Delivery Applications
by Omar Mertins, Patrick D. Mathews and Angelina Angelova
Nanomaterials 2020, 10(5), 963; https://doi.org/10.3390/nano10050963 - 18 May 2020
Cited by 67 | Viewed by 5871
Abstract
Nanostructure bicontinuous cubic phase self-assembled materials are receiving expanding applications as biocompatible delivery systems in various therapeutic fields. The functionalization of cubosome, spongosome, hexosome and liposome nanocarriers by pH-sensitive lipids and/or pH-sensitive polymer shells offers new opportunities for oral and topical drug delivery [...] Read more.
Nanostructure bicontinuous cubic phase self-assembled materials are receiving expanding applications as biocompatible delivery systems in various therapeutic fields. The functionalization of cubosome, spongosome, hexosome and liposome nanocarriers by pH-sensitive lipids and/or pH-sensitive polymer shells offers new opportunities for oral and topical drug delivery towards a new generation of cancer therapies. The electrochemical behavior of drug compounds may favor pH-triggered drug release as well. Here, we highlight recent investigations, which explore the phase behavior of mixed nonlamellar lipid/fatty acid or phospholipid systems for the design of pH-responsive and mucoadhesive drug delivery systems with sustained-release properties. X-ray diffraction and small-angle X-ray scattering (SAXS) techniques are widely used in the development of innovative delivery assemblies through detailed structural analyses of multiple amphiphilic compositions from the lipid/co-lipid/water phase diagrams. pH-responsive nanoscale materials and nanoparticles are required for challenging therapeutic applications such as oral delivery of therapeutic proteins and peptides as well as of poorly water-soluble substances. Perspective nanomedicine developments with smart cubosome nanocarriers may exploit compositions elaborated to overcome the intestinal obstacles, dual-drug loaded pH-sensitive liquid crystalline architectures aiming at enhanced therapeutic efficacy, as well as composite (lipid/polyelectrolyte) types of mucoadhesive controlled release colloidal cubosomal formulations for the improvement of the drugs’ bioavailability. Full article
(This article belongs to the Special Issue Progress in Pharmaceutical Applications of Lipid-Based Nanoparticles)
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