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Pharmaceutics
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Advances in Nanotechnology-Based Drug Delivery Systems
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Advances in Nanotechnology-Based Drug Delivery Systems

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

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 20196

Special Issue Editor

Dr. Carla Serri

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Guest Editor
Department of Medicine, Surgery and Pharmacy, University of Sassari, Via Muroni 23/a, 07100 Sassari, Italy
Interests: polymeric nanoparticles; nanomedicine; pharmaceutical technology; lipid nanoparticles; nanoprecipitation; nanoparticles loading poorly soluble drugs; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanotechnology is a scientific branch focused on designing, fabricating, and applying nanostructures and nanomaterials at the nanometer scale. There has been growing interest in using nanotechnologies to produce and investigate carriers for drug delivery. In this sense, nanocarriers (such as liposomes and derivatives, metal nanoparticles, carbon nanoparticles and nanotubes, nanocrystals, polymeric nanospheres, nanocapsules and micelles) can be used to control the release and delivery of Active Pharmaceutical Ingredients (APIs), enhance the dissolution of poorly soluble APIs and improve their bioavailability and decrease the side effects.

In this Special Issue of Pharmaceutics, original research articles and reviews regarding nanotechnology applications in the pharmaceutical field are welcome. Herein, we intend to highlight the advances in new technologies for the development of different types of nanocarriers via the use of green techniques and materials. Articles centred on formulation strategies to encapsulate biological macromolecules are particularly appreciated.

I look forward to receiving your contributions.

Dr. Carla Serri
Guest Editor

Manuscript Submission Information

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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

  • biomaterials
  • nanomedicine
  • nanotechnology
  • formulations
  • green production technologies
  • biological macromolecule nanoencapsulation

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Published Papers (10 papers)

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Research

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21 pages, 5231 KiB  
Article
Clarithromycin-Loaded Albumin-Based Nanoparticles for Improved Antibacterial and Anticancer Performance
by Walhan Alshaer, Shrouq Alsotari, Nour Aladaileh, Alaa Rifai, Aya Khalaf, Baidaa AlQuaissi, Bushra Sabbah, Hamdi Nsairat and Fadwa Odeh
Pharmaceutics 2025, 17(6), 729; https://doi.org/10.3390/pharmaceutics17060729 - 31 May 2025
Viewed by 638
Abstract
Background/Objectives: Clarithromycin (CLA) is a widely used antibiotic effective against a variety of bacterial strains, making it a common treatment for respiratory, skin, and soft tissue infections. Moreover, extensive studies have confirmed the anticancer activity of CLA against different cancers, particularly when combined [...] Read more.
Background/Objectives: Clarithromycin (CLA) is a widely used antibiotic effective against a variety of bacterial strains, making it a common treatment for respiratory, skin, and soft tissue infections. Moreover, extensive studies have confirmed the anticancer activity of CLA against different cancers, particularly when combined with conventional therapies. This study investigates the potential anticancer and antibacterial activities of developed CLA-loaded bovine serum albumin nanoparticles (CLA-BSA NPs), designed with optimized physicochemical properties to enhance drug delivery. Methods: The CLA-BSA NPs were synthesized using the desolvation method, followed by drug loading. Characterization techniques, including Dynamic Light Scattering (DLS), Fourier-Transform Infrared (FTIR) Spectroscopy, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Thermogravimetric Analysis (TGA). Results: The results confirmed that CLA interacts with BSA NPs through van der Waals forces. The performance of drug–nanocarrier interaction was further assessed through in vitro drug release studies. The release studies demonstrated that CLA had a robust release profile in reductive media, with a cumulative release of 50.9% in acetate buffer (pH 5.0) supplemented with 10 mM glutathione (GSH). Further biological activity assays were also conducted, including cell viability assays (MTT) and antibacterial activity tests. CLA-BSA NPs demonstrated anticancer activity against the lung cancer (A549) cell line, while showing minimal cytotoxicity on normal human dermal fibroblast (HDF) cells. The antibacterial activity was assessed against Streptococcus pyogenes, Bacillus cereus, and Staphylococcus aureus. Among the tested strains, Bacillus cereus exhibited the highest sensitivity, with a minimum inhibitory concentration (MIC) of 0.032 µg/mL, compared to 0.12 µg/mL for Staphylococcus aureus and >32 µg/mL for Streptococcus pyogenes. Conclusions: In conclusion, these findings highlight CLA-BSA NPs as a promising drug delivery system that enhances the anticancer and antibacterial efficacy of CLA. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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21 pages, 2228 KiB  
Article
Assessment of the Anti-Inflammatory Effectiveness of Diclofenac Encapsulated in Chitosan-Coated Lipid Microvesicles in Rats
by Ana-Maria Raluca Pauna, Liliana Mititelu Tartau, Alin Mihai Vasilescu, Angy Abu Koush, Ruxandra Teodora Stan, Marius Constatin Moraru, Cosmin Gabriel Popa, Liviu Ciprian Gavril, Roxana Florentina Gavril, Dragos Valentin Crauciuc, Ana Marina Radulescu and Cristinel Ionel Stan
Pharmaceutics 2025, 17(5), 607; https://doi.org/10.3390/pharmaceutics17050607 - 3 May 2025
Viewed by 608
Abstract
Background: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug (NSAID), but its conventional formulations may have limited efficacy and are associated with adverse effects. This study aimed to evaluate the anti-inflammatory and antioxidant effects of diclofenac encapsulated in chitosan-coated lipid microvesicles [...] Read more.
Background: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug (NSAID), but its conventional formulations may have limited efficacy and are associated with adverse effects. This study aimed to evaluate the anti-inflammatory and antioxidant effects of diclofenac encapsulated in chitosan-coated lipid microvesicles (DCF-m) compared to free DCF in a rat model of subacute inflammation. Method: DCF-m was prepared using L-α-phosphatidylcholine and coated with chitosan (CHIT). Subacute inflammation was induced using the cotton pellet granuloma model, and animals were divided into four groups (n = 5): a negative control group without granuloma receiving vehicle (double-distilled water), a control group with granuloma receiving vehicle, a group with granuloma treated with 15 mg/kg of free DCF, and a group with granuloma treated with 15 mg/kg of DCF-m. Results: Both DCF and DCF-m significantly reduced granuloma mass, body weight gain, and serum inflammatory markers compared to the control group with granuloma. Moreover, DCF-m treatment led to a more pronounced reduction in granulomatous inflammation and a greater enhancement of antioxidant enzyme activity than free DCF. Conclusions: These findings suggest that DCF-m exhibits superior anti-inflammatory and antioxidant properties compared to conventional diclofenac in a model of subacute inflammation. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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30 pages, 8769 KiB  
Article
Efficient and Rapid Microfluidics Production of Bio-Inspired Nanoparticles Derived from Bombyx mori Silkworm for Enhanced Breast Cancer Treatment
by Muhamad Hawari Mansor, Zijian Gao, Faith Howard, Jordan MacInnes, Xiubo Zhao and Munitta Muthana
Pharmaceutics 2025, 17(1), 95; https://doi.org/10.3390/pharmaceutics17010095 - 12 Jan 2025
Viewed by 1141
Abstract
Background/Objectives: In the quest for sustainable and biocompatible materials, silk fibroin (SF), derived from natural silk, has emerged as a promising candidate for nanoparticle production. This study aimed to fabricate silk fibroin particles (SFPs) using a novel swirl mixer previously presented by [...] Read more.
Background/Objectives: In the quest for sustainable and biocompatible materials, silk fibroin (SF), derived from natural silk, has emerged as a promising candidate for nanoparticle production. This study aimed to fabricate silk fibroin particles (SFPs) using a novel swirl mixer previously presented by our group, evaluating their characteristics and suitability for drug delivery applications, including magnetic nanoparticles and dual-drug encapsulation with curcumin (CUR) and 5-fluorouracil (5-FU). Methods: SFPs were fabricated via microfluidics-assisted desolvation using a swirl mixer, ensuring precise mixing kinetics. Comprehensive physicochemical characterisation, including size, polydispersity index (PDI), zeta potential, and secondary structure analysis, was conducted. Further, CUR/5-FU-loaded magnetic core SFPs were assessed for cytotoxicity in vitro using breast cancer cell lines and for biodistribution and targeting efficiency in a murine breast cancer model. Results: The swirl mixer produced SFPs with sizes below 200 nm and uniform distributions (PDI < 0.20) with size stability for up to 30 days. Encapsulation efficiencies were 37% for CUR and 82% for 5-FU, with sustained drug release profiles showing 50% of CUR and 70% of 5-FU released over 72 h. In vitro studies demonstrated sustained cytotoxic effects, and cell cycle arrest at the G2/M phase in breast cancer cell lines, with minimal toxicity in non-cancerous cells. Cellular uptake assays confirmed efficient drug delivery to the cytoplasm. In vivo biodistribution studies revealed increased tumour-specific drug accumulation with magnetic guidance. Haematoxylin & Eosin (H&E) staining indicated enhanced tumour necrosis in treated groups compared to controls. Conclusions: This study underscores the utility of the swirl mixer for efficient and scalable fabrication of bio-inspired SFPs, supporting their application in targeted cancer drug delivery. These findings align with and advance previous insights into the use of microfluidics and desolvation methods, paving the way for improved therapeutic strategies in breast cancer treatment. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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19 pages, 3385 KiB  
Article
Bioactive Properties and In Vitro Digestive Release of Cannabidiol (CBD) from Tailored Composites Based on Carbon Materials
by Karol Zapata, Angie D. Vélez, Jorge A. Correa, Francisco Carrasco-Marín, Benjamín A. Rojano, Camilo A. Franco and Farid B. Cortés
Pharmaceutics 2024, 16(9), 1132; https://doi.org/10.3390/pharmaceutics16091132 - 27 Aug 2024
Viewed by 1310
Abstract
The use of carriers to improve cannabidiol (CBD) bioavailability during digestion is at the forefront of research. The main objective of this research was to evaluate CBD bioactivity and develop CBD composites based on tailored carbon support to improve availability under digestive conditions. [...] Read more.
The use of carriers to improve cannabidiol (CBD) bioavailability during digestion is at the forefront of research. The main objective of this research was to evaluate CBD bioactivity and develop CBD composites based on tailored carbon support to improve availability under digestive conditions. The antioxidant capacity of CBD was evaluated using spectrophotometric methods, and anti-proliferative assays were carried out using human colon carcinoma cells (SW480). Twenty-four composites of CBD + carbon supports were developed, and CBD desorption tests were carried out under simulated digestive conditions. The antioxidant capacity of CBD was comparable to and superior to Butylhydrox-ytoluene (BHT), a commercial antioxidant. CBD reflected an IC-50 of 10,000 mg/L against SW480 cancer cells. CBD in biological systems can increase the shelf life of lipid and protein foods by 7 and 470 days, respectively. Finally, acid carbons showed major CBD adsorption related to electrostatic interactions, but basic carbons showed better delivery properties related to electrostatic repulsion. A tailored composite was achieved with a CBD load of 27 mg/g with the capacity to deliver 1.1 mg, 21.8 mg, and 4 mg to the mouth, stomach, and duodenum during 18 h, respectively. This is a pioneering study since the carriers were intelligently developed to improve CBD release. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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12 pages, 1413 KiB  
Article
Synthesis, Characterization, and Cytotoxicity Evaluation of Chlorambucil-Functionalized Mesoporous Silica Nanoparticles
by Juliana Camila Fischer Karnopp, Juliana Jorge, Jaqueline Rodrigues da Silva, Diego Boldo, Kristiane Fanti Del Pino Santos, Adriana Pereira Duarte, Gustavo Rocha de Castro, Ricardo Bentes de Azevedo, Ariadna Lafourcade Prada, Jesús Rafael Rodríguez Amado and Marco Antonio Utrera Martines
Pharmaceutics 2024, 16(8), 1086; https://doi.org/10.3390/pharmaceutics16081086 - 19 Aug 2024
Cited by 1 | Viewed by 1743
Abstract
This study describes the synthesis and characterization of chlorambucil (CLB)-functionalized mesoporous silica nanoparticles (MSNs) for potential application in cancer therapy. The nanoparticles were designed with a diameter between 20 and 50 nm to optimize cellular uptake and avoid rapid clearance from the bloodstream. [...] Read more.
This study describes the synthesis and characterization of chlorambucil (CLB)-functionalized mesoporous silica nanoparticles (MSNs) for potential application in cancer therapy. The nanoparticles were designed with a diameter between 20 and 50 nm to optimize cellular uptake and avoid rapid clearance from the bloodstream. The synthesis method involved modifying a previously reported technique to reduce particle size. Successful functionalization with CLB was confirmed through various techniques, including Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The cytotoxicity of the CLB-functionalized nanoparticles (MSN@NH2-CLB) was evaluated against human lung adenocarcinoma cells (A549) and colon carcinoma cells (CT26WT). The results suggest significantly higher cytotoxicity of MSN@NH2-CLB compared to unbound CLB, with improved selectivity towards cancer cells over normal cells. This suggests that MSN@NH2-CLB holds promise as a drug delivery system for targeted cancer therapy. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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23 pages, 7257 KiB  
Article
Green Solid Lipid Nanoparticles by Fatty Acid Coacervation: An Innovative Nasal Delivery Tool for Drugs Targeting Cerebrovascular and Neurological Diseases
by Annalisa Bozza, Valentina Bordano, Arianna Marengo, Elisabetta Muntoni, Elisabetta Marini, Loretta Lazzarato, Chiara Dianzani, Chiara Monge, Arianna Carolina Rosa, Luigi Cangemi, Maria Carmen Valsania, Barbara Colitti, Ezio Camisassa and Luigi Battaglia
Pharmaceutics 2024, 16(8), 1051; https://doi.org/10.3390/pharmaceutics16081051 - 8 Aug 2024
Cited by 1 | Viewed by 1888
Abstract
Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, [...] Read more.
Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood–brain barrier and avoiding hepatic metabolism. Nasal lipid nanocarriers, such as solid lipid nanoparticles, may increase the nasal retention and permeation of drugs. To this aim, green solid lipid nanoparticles, obtained by coacervation from natural soaps, are promising vehicles due to their specific lipid matrix composition and the unsaponifiable fraction, endowed with antioxidant and anti-inflammatory properties, and thus suitable for restoring the neurovascular unit function. In this experimental work, such green solid lipid nanoparticles, fully characterized from a physico-chemical standpoint, were loaded with a drug combination suitable for reverting hydrocephalus symptoms, allowing us to obtain a non-toxic formulation, a reduction in the production of the cerebrospinal fluid in vitro, and a vasoprotective effect on an isolated vessel model. The pharmacokinetics and biodistribution of fluorescently labelled nanoparticles were also tested in animal models. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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18 pages, 3072 KiB  
Article
Hyaluronic Acid-Based Nanoparticles Loaded with Rutin as Vasculo-Protective Tools against Anthracycline-Induced Endothelial Damages
by Carla Serri, Vincenzo Quagliariello, Iriczalli Cruz-Maya, Vincenzo Guarino, Nicola Maurea, Paolo Giunchedi, Giovanna Rassu and Elisabetta Gavini
Pharmaceutics 2024, 16(8), 985; https://doi.org/10.3390/pharmaceutics16080985 - 25 Jul 2024
Cited by 1 | Viewed by 1400
Abstract
Anthracycline-based therapies exert endothelial damages through peroxidation and the production of proinflammatory cytokines, resulting in a high risk of cardiovascular complications in cancer patients. Hyaluronic acid-based hybrid nanoparticles (LicpHA) are effective pharmacological tools that can target endothelial cells and deliver drugs or nutraceuticals. [...] Read more.
Anthracycline-based therapies exert endothelial damages through peroxidation and the production of proinflammatory cytokines, resulting in a high risk of cardiovascular complications in cancer patients. Hyaluronic acid-based hybrid nanoparticles (LicpHA) are effective pharmacological tools that can target endothelial cells and deliver drugs or nutraceuticals. This study aimed to prepared and characterized a novel LicpHA loaded with Rutin (LicpHA Rutin), a flavonoid with high antioxidant and anti-inflammatory properties, to protect endothelial cells against epirubicin-mediated endothelial damages. LicpHA Rutin was prepared using phosphatidylcholine, cholesterol, poloxamers, and hyaluronic acid by a modified nanoprecipitation technique. The chemical-physical characterization of the nanoparticles was carried out (size, zeta potential, morphology, stability, thermal analysis, and encapsulation efficiency). Cytotoxicity studies were performed in human endothelial cells exposed to epirubicin alone or in combination with Free-Rutin or LicpHA Rutin. Anti-inflammatory studies were performed through the intracellular quantification of NLRP-3, MyD-88, IL-1β, IL-6, IL17-α, TNF-α, IL-10, and IL-4 using selective ELISA methods. Morphological studies via TEM and image analysis highlighted a heterogeneous population of LicpHA particles with non-spherical shapes (circularity equal to 0.78 ± 0.14), and the particle size was slightly affected by Rutin entrapment (the mean diameter varied from 179 ± 4 nm to 209 ± 4 nm). Thermal analysis and zeta potential analyses confirmed the influence of Rutin on the chemical-physical properties of LicpHA Rutin, mainly indicated by the decrease in the surface negative charge (from −35 ± 1 mV to −30 ± 0.5 mV). Cellular studies demonstrated that LicpHA Rutin significantly reduced cell death and inflammation when compared to epirubicin alone. The levels of intracellular NLRP3, Myd-88, and proinflammatory cytokines were significantly lower in epirubicin + LicpHA Rutin-exposed cells when compared to epirubicin groups (p < 0.001). Hyaluronic acid-based nanoparticles loaded with Rutin exerts significant vasculo-protective properties during exposure to anthracyclines. The overall picture of this study pushes towards preclinical and clinical studies in models of anthracycline-induced vascular damages. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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23 pages, 19779 KiB  
Article
Optimizing mRNA-Loaded Lipid Nanoparticles as a Potential Tool for Protein-Replacement Therapy
by Rocío Gambaro, Ignacio Rivero Berti, María José Limeres, Cristián Huck-Iriart, Malin Svensson, Silvia Fraude, Leah Pretsch, Shutian Si, Ingo Lieberwirth, Stephan Gehring, Maximiliano Cacicedo and Germán Abel Islan
Pharmaceutics 2024, 16(6), 771; https://doi.org/10.3390/pharmaceutics16060771 - 6 Jun 2024
Cited by 7 | Viewed by 4805
Abstract
Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform for treating metabolic diseases. Four distinct lipid mixes (LMs) were formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability and homogeneity [...] Read more.
Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform for treating metabolic diseases. Four distinct lipid mixes (LMs) were formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability and homogeneity with a mean size of 75 to 90 nm, confirmed by cryo-TEM and SAXS studies. High mRNA encapsulation (95–100%) was achieved. LNPs effectively delivered EGFP-encoding mRNA to HepG2 and DC2.4 cell lines. LNPs induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs), revealing that LM1, LM2, and LM4 induced 1.5- to 4-fold increases in IL-8, TNF-α, and MCP-1 levels, while LM3 showed minimal changes. Reporter mRNA expression was observed in LNP-treated PBMCs. Hemotoxicity studies confirmed formulation biocompatibility with values below 2%. In vivo biodistribution in mice post intramuscular injection showed significant mRNA expression, mainly in the liver. The modification of LNP components influenced reactogenicity, inflammatory response, and mRNA expression, offering a promising platform for selecting less reactogenic carriers suitable for repetitive dosing in metabolic disease treatment. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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Review

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22 pages, 2048 KiB  
Review
Navigating the Clinical Landscape of Liposomal Therapeutics in Cancer Treatment
by Andreja Kozak, Ernestina Lavrih, Georgy Mikhaylov, Boris Turk and Olga Vasiljeva
Pharmaceutics 2025, 17(2), 276; https://doi.org/10.3390/pharmaceutics17020276 - 18 Feb 2025
Cited by 3 | Viewed by 954
Abstract
Liposome-based targeted drug delivery systems represent a significant advancement in pharmaceutical science, offering distinct advantages that enhance the efficacy and safety of various therapies. These versatile carriers can encapsulate both hydrophilic and hydrophobic drugs, making them particularly valuable in clinical settings. This review [...] Read more.
Liposome-based targeted drug delivery systems represent a significant advancement in pharmaceutical science, offering distinct advantages that enhance the efficacy and safety of various therapies. These versatile carriers can encapsulate both hydrophilic and hydrophobic drugs, making them particularly valuable in clinical settings. This review explores the critical role of liposomal formulations in improving drug pharmacokinetics and minimizing side effects, especially in oncology, where targeted delivery to tumor cells is essential. Outlining the properties of different types of liposomes, we focus on the effects of these properties on the liposomes’ targeting and drug release capabilities through innovative surface modifications and describe the most common methods of liposome preparation and characterization. Furthermore, this review provides an in-depth analysis of the properties and composition of liposomal-based nanocarriers, with a unique focus on ongoing clinical trials and recently approved therapies. It offers a comprehensive overview of the latest advancements in pre-clinical research and highlights the critical progress in clinical development, offering insights into the clinical impact and regulatory approvals. Ultimately, this review underscores the transformative potential of liposomal nanocarriers in modern therapeutics, suggesting avenues for future innovations and clinical breakthroughs. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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26 pages, 6769 KiB  
Review
Effect of Lipid Nanoparticle Physico-Chemical Properties and Composition on Their Interaction with the Immune System
by Laura Catenacci, Rachele Rossi, Francesca Sechi, Daniela Buonocore, Milena Sorrenti, Sara Perteghella, Marco Peviani and Maria Cristina Bonferoni
Pharmaceutics 2024, 16(12), 1521; https://doi.org/10.3390/pharmaceutics16121521 - 26 Nov 2024
Cited by 10 | Viewed by 4095
Abstract
Lipid nanoparticles (LNPs) have shown promise as a delivery system for nucleic acid-based therapeutics, including DNA, siRNA, and mRNA vaccines. The immune system plays a critical role in the response to these nanocarriers, with innate immune cells initiating an early response and adaptive [...] Read more.
Lipid nanoparticles (LNPs) have shown promise as a delivery system for nucleic acid-based therapeutics, including DNA, siRNA, and mRNA vaccines. The immune system plays a critical role in the response to these nanocarriers, with innate immune cells initiating an early response and adaptive immune cells mediating a more specific reaction, sometimes leading to potential adverse effects. Recent studies have shown that the innate immune response to LNPs is mediated by Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs), which recognize the lipid components of the nanoparticles. This recognition can trigger the activation of inflammatory pathways and the production of cytokines and chemokines, leading to potential adverse effects such as fever, inflammation, and pain at the injection site. On the other hand, the adaptive immune response to LNPs appears to be primarily directed against the protein encoded by the mRNA cargo, with little evidence of an ongoing adaptive immune response to the components of the LNP itself. Understanding the relationship between LNPs and the immune system is critical for the development of safe and effective nucleic acid-based delivery systems. In fact, targeting the immune system is essential to develop effective vaccines, as well as therapies against cancer or infections. There is a lack of research in the literature that has systematically studied the factors that influence the interaction between LNPs and the immune system and further research is needed to better elucidate the mechanisms underlying the immune response to LNPs. In this review, we discuss LNPs’ composition, physico-chemical properties, such as size, shape, and surface charge, and the protein corona formation which can affect the reactivity of the immune system, thus providing a guide for the research on new formulations that could gain a favorable efficacy/safety profile. Full article
(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems)
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