Lipid Nanosystems for Local Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 32645

Special Issue Editors


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Guest Editor
Fernando Pessoa Energy, Environment and Health Research Unit/Biomedical Research Center (FP-ENAS/CEBIMED), Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
Interests: controlled release; nanostructured lipid carriers; nanomaterials; dynamic light scattering; high-pressure homogenization; preformulation studies

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Guest Editor
1. FP-BHS—Biomedical and Health Sciences Research Unit, FP-I3ID—Instituto de Investigação, Inovação e Desenvolvimento, Faculty of Health Science, Fernando Pessoa University, 4200-150 Porto, Portugal
2. UCIBIO—Applied Molecular Biosciences Unit, MedTech—Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 050-313 Porto, Portugal
Interests: bioactive delivery systems; lipid-based nanosystems; hybrid nanosystems; controlled delivery; multifunctional nanosystems
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Special Issue Information

Dear Colleagues,

Nanosystems provide an appealing approach to pharmacological therapy, with the possibility of enhancing performance and covercoming constraints of conventional therapies, thus adding substantial value to some of the already available formulations. Among nanosystems, the lipid ones (e.g., liposomes, solid lipid nanoparticles, nanostructures lipid carriers, and nanoemulsions) have enormous potential in the field of drug delivery because of their lipid biocompatibility, low toxicity, and versatility. Currently, the development of nanomedicines based on lipid nanosystems capable of delivering therapeutic drugs to a  desired body site is an attractive area of research in the pharmaceutical field. The major advantage of local drug delivery is that the drug concentration in a specific desired site can be enhanced, reducing the toxicity to other nontargeted locations. Local drug delivery using nanosystems is accomplished in two different ways: direct local placement (e.g., local administration at the intended site of use) or systemic administration, either targeted or triggered. This Special Issue seeks to present a collection of innovative studies describing recent advances in the development of lipid nanosystems suited for local drug delivery, using both strategies (i.e., localized delivery or targeted/triggered strategies), and highlighting their advantages in this research area.

Dr. José Catita
Dr. Carla M. Lopes
Guest Editors

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Keywords

  • lipid nanosystems
  • local drug delivery
  • liposomes
  • solid lipid nanoparticles (SLN)
  • nanostructures lipid carriers (NLC)
  • nanoemulsions
  • local administration
  • systemic administration
  • triggering (local and remote)
  • targeting

Published Papers (11 papers)

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Editorial

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4 pages, 202 KiB  
Editorial
Editorial on Special Issue “Lipid Nanosystems for Local Drug Delivery”
by José Catita and Carla M. Lopes
Pharmaceutics 2023, 15(7), 1970; https://doi.org/10.3390/pharmaceutics15071970 - 18 Jul 2023
Viewed by 808
Abstract
Nanosystems provide an attractive approach to pharmacological therapy, with the possibility of enhancing the performance and overcoming the constraints of conventional therapies, thus adding substantial value to some of the already available formulations [...] Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)

Research

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24 pages, 2757 KiB  
Article
Nanoemulsion Loaded with Clotrimazole Based on Rapeseed Oil for Potential Vaginal Application—Development, Initial Assessment, and Pilot Release Studies
by Michał Smoleński, Susanne Muschert, Dorota Haznar-Garbacz and Katarzyna Małolepsza-Jarmołowska
Pharmaceutics 2023, 15(5), 1437; https://doi.org/10.3390/pharmaceutics15051437 - 8 May 2023
Cited by 1 | Viewed by 1863
Abstract
Vaginal candidiasis (VC) is an emerging global hardly treated health issue affecting millions of women worldwide. In this study, the nanoemulsion consisting of clotrimazole (CLT), rapeseed oil, Pluronic F-68, Span 80, PEG 200, and lactic acid was prepared using high-speed and high-pressure homogenization. [...] Read more.
Vaginal candidiasis (VC) is an emerging global hardly treated health issue affecting millions of women worldwide. In this study, the nanoemulsion consisting of clotrimazole (CLT), rapeseed oil, Pluronic F-68, Span 80, PEG 200, and lactic acid was prepared using high-speed and high-pressure homogenization. Yielded formulations were characterized by an average droplet size of 52–56 nm, homogenous size distribution by volume, and a polydispersity index (PDI) < 0.2. The osmolality of nanoemulsions (NEs) fulfilled the recommendations of the WHO advisory note. NEs were stable throughout 28 weeks of storage. The stationary and dynamic (USP apparatus IV) pilot study of the changes of free CLT over time for NEs, as well as market cream and CLT suspension as references, were conducted. Test results of the changes in the amount of free CLT released from the encapsulated form were not coherent; in the stationary method, NEs yielded up to 27% of the released CLT dose within 5 h, while in the USP apparatus IV method, NEs released up to 10% of the CLT dose. NEs are promising carriers for vaginal drug delivery in the treatment of VC; however, further development of the final dosage form and harmonized release or dissolution testing protocols are needed. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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25 pages, 11627 KiB  
Article
Preparation and In Vitro Characterization of Alkyl Polyglucoside-Based Microemulsion for Topical Administration of Curcumin
by Cristina Scomoroscenco, Mircea Teodorescu, Cristina Lavinia Nistor, Ioana Catalina Gifu, Cristian Petcu, Daniel Dumitru Banciu, Adela Banciu and Ludmila Otilia Cinteza
Pharmaceutics 2023, 15(5), 1420; https://doi.org/10.3390/pharmaceutics15051420 - 6 May 2023
Cited by 5 | Viewed by 2165
Abstract
The skin is a complex and selective system from the perspective of permeability to substances from the external environment. Microemulsion systems have demonstrated a high performance in encapsulating, protecting and transporting active substances through the skin. Due to the low viscosity of microemulsion [...] Read more.
The skin is a complex and selective system from the perspective of permeability to substances from the external environment. Microemulsion systems have demonstrated a high performance in encapsulating, protecting and transporting active substances through the skin. Due to the low viscosity of microemulsion systems and the importance of a texture that is easy to apply in the cosmetic and pharmaceutical fields, gel microemulsions are increasingly gaining more interest. The aim of this study was to develop new microemulsion systems for topical use; to identify a suitable water-soluble polymer in order to obtain gel microemulsions; and to study the efficacy of the developed microemulsion and gel microemulsion systems in the delivery of a model active ingredient, namely curcumin, into the skin. A pseudo-ternary phase diagram was developed using AKYPO® SOFT 100 BVC, PLANTACARE® 2000 UP Solution and ethanol as a surfactant mix; caprylic/capric triglycerides, obtained from coconut oil, as the oily phase; and distilled water. To obtain gel microemulsions, sodium hyaluronate salt was used. All these ingredients are safe for the skin and are biodegradable. The selected microemulsions and gel microemulsions were physicochemically characterized by means of dynamic light scattering, electrical conductivity, polarized microscopy and rheometric measurements. To evaluate the efficiency of the selected microemulsion and gel microemulsion to deliver the encapsulated curcumin, an in vitro permeation study was performed. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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31 pages, 6531 KiB  
Article
Development of Nanoemulsions for Topical Application of Mupirocin
by Bahjat Alhasso, Muhammad Usman Ghori and Barbara R. Conway
Pharmaceutics 2023, 15(2), 378; https://doi.org/10.3390/pharmaceutics15020378 - 22 Jan 2023
Cited by 8 | Viewed by 2805
Abstract
Mupirocin (MUP) is a topical antibacterial agent used to treat superficial skin infections but has limited application due to in vivo inactivation and plasma protein binding. A nanoemulsion formulation has the potential to enhance the delivery of mupirocin into the skin. MUP-loaded nanoemulsions [...] Read more.
Mupirocin (MUP) is a topical antibacterial agent used to treat superficial skin infections but has limited application due to in vivo inactivation and plasma protein binding. A nanoemulsion formulation has the potential to enhance the delivery of mupirocin into the skin. MUP-loaded nanoemulsions were prepared using eucalyptus oil (EO) or eucalyptol (EU), Tween® 80 (T80) and Span® 80 (S80) as oil phase (O), surfactant (S) and cosurfactant (CoS). The nanoemulsions were characterised and their potential to enhance delivery was assessed using an in vitro skin model. Optimised nanoemulsion formulations were prepared based on EO (MUP-NE EO) and EU (MUP-NE EU) separately. MUP-NE EO had a smaller size with mean droplet diameter of 35.89 ± 0.68 nm and narrower particle size index (PDI) 0.10 ± 0.02 nm compared to MUP-NE EU. Both nanoemulsion formulations were stable at 25 °C for three months with the ability to enhance the transdermal permeation of MUP as compared to the control, Bactroban® cream. Inclusion of EU led to a two-fold increase in permeation of MUP compared to the control, while EO increased the percentage by 48% compared to the control. Additionally, more MUP was detected in the skin after 8 h following MUP-NE EU application, although MUP deposition from MUP-NE EO was higher after 24 h. It may be possible, through choice of essential oil to design nanoformulations for both acute and prophylactic management of topical infections. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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19 pages, 3699 KiB  
Article
pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance
by Patrícia V. Teixeira, Filomena Adega, Paula Martins-Lopes, Raul Machado, Carla M. Lopes and Marlene Lúcio
Pharmaceutics 2023, 15(2), 326; https://doi.org/10.3390/pharmaceutics15020326 - 18 Jan 2023
Cited by 8 | Viewed by 2285
Abstract
Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions [...] Read more.
Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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16 pages, 2449 KiB  
Article
Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System
by Oxana Semyachkina-Glushkovskaya, Alexander Shirokov, Inna Blokhina, Valeria Telnova, Elena Vodovozova, Anna Alekseeva, Ivan Boldyrev, Ivan Fedosov, Alexander Dubrovsky, Alexandr Khorovodov, Andrey Terskov, Arina Evsukova, Daria Elovenko, Viktoria Adushkina, Maria Tzoy, Ilana Agranovich, Jürgen Kurths and Edik Rafailov
Pharmaceutics 2023, 15(1), 36; https://doi.org/10.3390/pharmaceutics15010036 - 22 Dec 2022
Cited by 16 | Viewed by 2318
Abstract
The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to [...] Read more.
The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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36 pages, 6609 KiB  
Article
Microemulsions as Lipid Nanosystems Loaded into Thermoresponsive In Situ Microgels for Local Ocular Delivery of Prednisolone
by Rania Hamed, Amani D. Abu Kwiak, Yasmeen Al-Adhami, Alaa M. Hammad, Rana Obaidat, Osama H. Abusara and Rana Abu Huwaij
Pharmaceutics 2022, 14(9), 1975; https://doi.org/10.3390/pharmaceutics14091975 - 19 Sep 2022
Cited by 13 | Viewed by 1977
Abstract
This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a [...] Read more.
This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25–0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1–10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (−21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37–5.81), surface tension (30.96–38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1–23.9 nm and −1.34 to −10.25 mV, respectively), phase transition temperature (25.3–36 °C), and gelation time (1.44–2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16–24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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23 pages, 35550 KiB  
Article
Design, Manufacturing, Characterization and Evaluation of Lipid Nanocapsules to Enhance the Biopharmaceutical Properties of Efavirenz
by Grady K. Mukubwa, Justin B. Safari, Roderick B. Walker and Rui W. M. Krause
Pharmaceutics 2022, 14(7), 1318; https://doi.org/10.3390/pharmaceutics14071318 - 21 Jun 2022
Cited by 1 | Viewed by 2767
Abstract
Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as [...] Read more.
Despite their incredible contribution to fighting viral infections, antiviral viral resistance is an increasing concern and often arises due to unfavorable physicochemical and biopharmaceutical properties. To address this kind of issue, lipid nanocapsules (LNC) are developed in this study, using efavirenz (EFV) as a drug model. EFV solubility was assessed in water, Labrafac Lipophile and medium chain triglycerides oil (MCT oil). EFV turned out to be more soluble in the two latter dissolving media (solubility > 250 mg/mL); hence, given its affordability, MCT oil was used for LNC formulation. LNC were prepared using a low-energy method named phase inversion, and following a design of experiments process. This one resulted in polynomial models that predicted LNC particle size, polydispersity index and zeta potential that were, respectively, around 50 nm, below 0.2 and below −33 mV, for the optimized formulations. Once synthesized, we were able to achieve an encapsulation efficacy of 87%. On the other hand, high EFV release from the LNC carrier was obtained in neutral medium as compared to acid milieu (pH 4) with, respectively, 42 and 27% EFV release within 74 h. Other characterization techniques were applied and further supported the successful encapsulation of EFV in LNCs in an amorphous form. Stability studies revealed that the developed LNC were quite stable over the period of 28 days. Ultimately, LNCs have been demonstrated to improve the biopharmaceutical properties of EFV and could therefore be used to fight against antiviral resistance. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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Review

Jump to: Editorial, Research

28 pages, 1011 KiB  
Review
Use of Microfluidics to Prepare Lipid-Based Nanocarriers
by Alicia Vogelaar, Samantha Marcotte, Jiaqi Cheng, Benazir Oluoch and Jennica Zaro
Pharmaceutics 2023, 15(4), 1053; https://doi.org/10.3390/pharmaceutics15041053 - 24 Mar 2023
Cited by 10 | Viewed by 4519
Abstract
Lipid-based nanoparticles (LBNPs) are an important tool for the delivery of a diverse set of drug cargoes, including small molecules, oligonucleotides, and proteins and peptides. Despite their development over the past several decades, this technology is still hindered by issues with the manufacturing [...] Read more.
Lipid-based nanoparticles (LBNPs) are an important tool for the delivery of a diverse set of drug cargoes, including small molecules, oligonucleotides, and proteins and peptides. Despite their development over the past several decades, this technology is still hindered by issues with the manufacturing processes leading to high polydispersity, batch-to-batch and operator-dependent variability, and limits to the production volumes. To overcome these issues, the use of microfluidic techniques in the production of LBNPs has sharply increased over the past two years. Microfluidics overcomes many of the pitfalls seen with conventional production methods, leading to reproducible LBNPs at lower costs and higher yields. In this review, the use of microfluidics in the preparation of various types of LBNPs, including liposomes, lipid nanoparticles, and solid lipid nanoparticles for the delivery of small molecules, oligonucleotides, and peptide/protein drugs is summarized. Various microfluidic parameters, as well as their effects on the physicochemical properties of LBNPs, are also discussed. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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47 pages, 10611 KiB  
Review
Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications
by Nakamwi Akombaetwa, Ange B. Ilangala, Lorraine Thom, Patrick B. Memvanga, Bwalya Angel Witika and Aristote B. Buya
Pharmaceutics 2023, 15(2), 656; https://doi.org/10.3390/pharmaceutics15020656 - 15 Feb 2023
Cited by 20 | Viewed by 4212
Abstract
Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, [...] Read more.
Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, is low skin permeability. The skin is a healthy barrier that serves as the body’s primary defence mechanism against foreign particles. New advances in skin delivery (both topical and transdermal) depend on overcoming the challenges associated with drug molecule permeation and skin irritation. These limitations can be overcome by employing new approaches such as lipid nanosystems. Due to their advantages (such as easy scaling, low cost, and remarkable stability) these systems have attracted interest from the scientific community. However, for a successful formulation, several factors including particle size, surface charge, components, etc. have to be understood and controlled. This review provided a brief overview of the structure of the skin as well as the different pathways of nanoparticle penetration. In addition, the main factors influencing the penetration of nanoparticles have been highlighted. Applications of lipid nanosystems for dermal and transdermal delivery, as well as regulatory aspects, were critically discussed. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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22 pages, 759 KiB  
Review
Lipid Nanoparticles Functionalized with Antibodies for Anticancer Drug Therapy
by Ana Camila Marques, Paulo C. Costa, Sérgia Velho and Maria Helena Amaral
Pharmaceutics 2023, 15(1), 216; https://doi.org/10.3390/pharmaceutics15010216 - 8 Jan 2023
Cited by 22 | Viewed by 5378
Abstract
Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity [...] Read more.
Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current “state-of-the-art” in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success. Full article
(This article belongs to the Special Issue Lipid Nanosystems for Local Drug Delivery)
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