Lipid Nanoparticles in the Treatment of Neurological and Other Aging Related Disorders

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (10 March 2022) | Viewed by 19135

Special Issue Editors

LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: nanotechnology and interfacial phenomena; effects of fluorinated systems and peptides on the aggregation of amyloid beta peptide; conformational studies of proteins and peptides self-organized systems and polymer surfaces; design and production of inorganic and polymeric nano-systems for pharmaceutical and food applications
Special Issues, Collections and Topics in MDPI journals
1. LEPABE–Laboratory for Process Engineering, Environment, Biotechnology and Energy, R. Dr. Roberto Frias, 4200-465 Porto, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: novel nanoengineered biomaterials for therapeutic applications; fluorinated peptide and active molecule interactions with surfaces and lipid model membranes; design of inhibitors of Alzheimer's fibrillogenesis; antibody-directed nanocarriers for Alzheimer’s disease; electrochemical immunosensors for detection of degenerative disease biomarkers; air pollutants/exposure risk assessment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Solid Lipid Nanoparticles (SLN) are promising nanocarriers composed by lipids. This type of nanoparticles revels outstanding characteristics, due to being stable, soluble in water, biocompatible, and biodegradable. Their size is between 40 to 200 nm, providing them the ability to bypass liver and spleen filtration, and escape from the reticulo-endothelial system. Their synthesis is cheap, highly reproducible, and does not require organic solvents. SLNs can be stable for about 3 years, and the drug release can be controlled over several weeks. Also, the NPs’ surface can be easily modified with targeting ligands to more efficiently reach the brain tissue. Thus, these nanosystems could be a suitable approach for the transport of drugs for treatment of Alzheimer´s disease, Parkinson’s’ disease, brain tumors, and other diseases.

This Special Issue aims to focus the recent progress of SLN formulations, including their potential as drug carriers to transport drugs to the brain area to treat neurological diseases.

Dr. Joana  A. Loureiro
Prof. Dr. Maria do Carmo Pereira
Guest Editors

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Keywords

  • solid lipid nanoparticles
  • solid lipid nanoparticles formulations
  • neurological diseases
  • alzheimer’s disease
  • parkinson’s disease
  • nanoparticles
  • drug delivery systems
  • nanocarriers

Published Papers (4 papers)

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Research

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17 pages, 2529 KiB  
Article
Lipid Nanoparticles Containing Mixtures of Antioxidants to Improve Skin Care and Cancer Prevention
by Catarina Gonçalves, Maria João Ramalho, Renata Silva, Vera Silva, Rita Marques-Oliveira, Ana Catarina Silva, Maria Carmo Pereira and Joana A. Loureiro
Pharmaceutics 2021, 13(12), 2042; https://doi.org/10.3390/pharmaceutics13122042 - 30 Nov 2021
Cited by 11 | Viewed by 2549
Abstract
Oxidative stress, triggered by UV radiation, is one of the major causes of free radical-associated disorders, such as skin cancer. The application of natural compounds (NCs) with antioxidant effects can attenuate free radicals’ accumulation and, therefore, provide a strategy for skin care and [...] Read more.
Oxidative stress, triggered by UV radiation, is one of the major causes of free radical-associated disorders, such as skin cancer. The application of natural compounds (NCs) with antioxidant effects can attenuate free radicals’ accumulation and, therefore, provide a strategy for skin care and cancer prevention. In this work, three natural compounds, naringenin, nordihydroguaiaretic acid (NDGA), and kaempferol, were encapsulated into nanostructured lipid carriers (NLCs) aiming for the development of a formulation for cutaneous application with antioxidant properties. For the experiments, different formulation parameters were evaluated to optimize the NLCs that showed a diameter around 200 nm, which is an adequate particle size for incorporation in cosmetics. Transmission electron microscopy (TEM) analysis confirmed the NLCs’ typical spherical morphology. Encapsulation efficiency (EE) and loading capacity (LC) values revealed an effective production process, with EEs over 90% and LCs near the maximum value. The developed NLCs revealed a prolonged in vitro release of the natural compounds. The NLCs were stable under storage conditions, maintaining their psychochemical characteristics for 30 days. Additionally, they did not show any physical instability in accelerated stability studies, which also suggests long-term stability. Finally, the NCs antioxidant activity was evaluated. Interestingly, the NDGA and kaempferol mixture provided an antioxidant synergic effect. The NLC formulations’ cytotoxicity was tested in vitro in immortalized human keratinocytes (HaCaT). In addition, putative antioxidant effects of the developed NLC formulations against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress were studied, and the NDGA-loaded NLC was revealed to be the one with the most protective effect. Therefore, we concluded that the naringenin, NDGA, and kaempferol incorporation into NLCs constitutes a promising strategy to increase their bioavailability and delivery to the skin. Full article
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13 pages, 1036 KiB  
Article
Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia
by Damiana Scuteri, Roberta Cassano, Sonia Trombino, Rossella Russo, Hirokazu Mizoguchi, Chizuko Watanabe, Kengo Hamamura, Soh Katsuyama, Takaaki Komatsu, Luigi Antonio Morrone, Laura Rombolà, Annagrazia Adornetto, Annarita S. Laganà, Maria Tiziana Corasaniti, Paolo Tonin, Shinobu Sakurada, Tsukasa Sakurada, Pierluigi Nicotera and Giacinto Bagetta
Pharmaceutics 2021, 13(3), 379; https://doi.org/10.3390/pharmaceutics13030379 - 12 Mar 2021
Cited by 34 | Viewed by 3630
Abstract
Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is [...] Read more.
Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia. Therefore, the aim of this study was to engineer a nanotechnology delivery system based on solid lipid nanoparticles loaded with bergamot essential oil (BEO) and devised in the pharmaceutical form of an odorless cream (NanoBEO) to confirm its analgesic efficacy for further development and application to control agitation in dementia. BEO has proven strong antinociceptive and anti-allodynic properties and, in its bergapten-free form, it is completely devoid of phototoxicity. NanoBEO has been studied in vivo confirming the previously reported analgesic activity of BEO to which is now added its anti-itching properties. Due to the nanotechnology delivery system, the stability of titrated BEO components is guaranteed. Finally, the latter invention, currently under patent consideration, is smell-devoid allowing efficacy and safety to be established in double-blind clinical trials; until now the latter studies have been impeded in aromatherapy by the strong odor of essential oils. A clinical trial NCT04321889 has been designed to provide information about the efficacy and safety of NanoBEO on agitation and pain in patients suffering from severe dementia. Full article
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26 pages, 4251 KiB  
Article
Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
by Saif Ahmad Khan, Saleha Rehman, Bushra Nabi, Ashif Iqubal, Nida Nehal, Usama A. Fahmy, Sabna Kotta, Sanjula Baboota, Shadab Md and Javed Ali
Pharmaceutics 2020, 12(11), 1059; https://doi.org/10.3390/pharmaceutics12111059 - 06 Nov 2020
Cited by 47 | Viewed by 3026
Abstract
Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be [...] Read more.
Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir. Full article
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Review

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36 pages, 4360 KiB  
Review
Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB
by Mantosh Kumar Satapathy, Ting-Lin Yen, Jing-Shiun Jan, Ruei-Dun Tang, Jia-Yi Wang, Rajeev Taliyan and Chih-Hao Yang
Pharmaceutics 2021, 13(8), 1183; https://doi.org/10.3390/pharmaceutics13081183 - 31 Jul 2021
Cited by 82 | Viewed by 8691
Abstract
The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of [...] Read more.
The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics. Full article
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