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Pharmaceutics
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Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery
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Nanostructured Lipid Carriers: Design, Properties and Applications in 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 (10 October 2023) | Viewed by 39458

Special Issue Editors

Dr. Anna Czajkowska-Kośnik

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Guest Editor
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland
Interests: solid dispersions; lipid carriers; low solubility; pharmaceutical technology; topical drug delivery; formulation and characterization of dosage forms; drug release; skin permeation
Special Issues, Collections and Topics in MDPI journals
Dr. Magdalena Wróblewska

E-Mail Website
Guest Editor
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland
Interests: lipid carriers; pharmaceutical technology; drug formulation; characterization of dosage forms; solubilization techniques; polymers; antimicrobial activity; skin penetration; topical drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanostructured lipid carriers (NLCs) are one of the lipid-based nanosystems reported as alternatives to emulsions, liposomes, microparticles and solid lipid nanoparticles (SLNs). NLCs are composed of both solid and liquid lipids as core matrix, usually with biocompatible and biodegradable properties. These nanosystems are widely described by many researchers, and have demonstrated application in many fields, including biomedical, pharmaceutical and cosmetic industries. The most significant advantages of these dosage forms include increased solubility, the protection of labile active substances, enhanced storage stability, improved permeability and bioavailability, and the ability to obtain controlled or targeted release. These benefits make it possible to reduce the frequency of drug administration, limit the risk of adverse effects, and promote patient comfort.

This Special Issue will be a collection of full papers, short communications, and review papers dedicated to the latest advances in nanostructured lipid carriers. Readers will find new information about NLCs, focused on issues such as structure, preparation techniques, characterization, and various applications in drug delivery. Studies offering innovative methodologies and new applications of nanostructured lipid carriers are also welcome.

Dr. Anna Czajkowska-Kośnik
Dr. Magdalena Wróblewska
Guest Editors

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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

  • lipid nanocarriers
  • drug delivery
  • nanocarriers
  • lipids
  • improved drug bioavailability
  • formulation and dosage form development
  • solubilization technology
  • controlled release
  • various routes of administration
  • synthesis and characterization

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Published Papers (8 papers)

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Research

Jump to: Review

16 pages, 4781 KiB  
Article
Encapsulation of Thymol in Gelatin Methacryloyl (GelMa)-Based Nanoniosome Enables Enhanced Antibiofilm Activity and Wound Healing
by Maryam Moghtaderi, Saba Bazzazan, Ghazal Sorourian, Maral Sorourian, Yasaman Akhavanzanjani, Hassan Noorbazargan and Qun Ren
Pharmaceutics 2023, 15(6), 1699; https://doi.org/10.3390/pharmaceutics15061699 - 9 Jun 2023
Cited by 11 | Viewed by 2557
Abstract
Non-healing wounds impose huge cost on patients, healthcare, and society, which are further fortified by biofilm formation and antimicrobial resistance (AMR) problems. Here, Thymol, an herbal antimicrobial agent, is utilized to combat AMR. For efficient delivery of Thymol gelatin methacryloyl (GelMa), a hydrophilic [...] Read more.
Non-healing wounds impose huge cost on patients, healthcare, and society, which are further fortified by biofilm formation and antimicrobial resistance (AMR) problems. Here, Thymol, an herbal antimicrobial agent, is utilized to combat AMR. For efficient delivery of Thymol gelatin methacryloyl (GelMa), a hydrophilic polymeric hydrogel with excellent biocompatibility combined with niosome was used to encapsulate Thymol. After optimization of the niosomal Thymol (Nio–Thymol) in the company of GelMa (Nio–Thymol@GelMa) to achieve maximum entrapment efficiency, minimum size, and low polydispersity index, the Thymol release peaked at 60% and 42% from Nio–Thymol@GelMa in medium with pH values of 6.5 and 7.4 after 72 h, respectively. Furthermore, Nio–Thymol@GelMa demonstrated higher antibacterial and anti-biofilm activity than Nio–Thymol and free Thymol against both Gram-negative and Gram-positive bacteria. Interestingly, compared with other obtained formulations, Nio–Thymol@GelMa also led to greater enhancement of migration of human dermal fibroblasts in vitro, and higher upregulation of the expression of certain growth factors such as FGF-1, and matrix metalloproteinases such as MMP-2 and MMP-13. These results suggest that Nio–Thymol@GelMa can represent a potential drug preparation for Thymol to enhance the wound healing process and antibacterial efficacy. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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21 pages, 2924 KiB  
Article
Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity
by Mohamed F. Zaky, Mohamed A. Megahed, Taha M. Hammady, Shadeed Gad, Mamdouh Mostafa Ghorab and Khalid M. El-Say
Pharmaceutics 2023, 15(1), 80; https://doi.org/10.3390/pharmaceutics15010080 - 27 Dec 2022
Cited by 11 | Viewed by 3873
Abstract
Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier [...] Read more.
Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y1), zeta potential (Y2), and entrapment efficiency percent (Y3) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y1, Y2, and Y3, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and Cmax by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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16 pages, 3035 KiB  
Article
Stability of Non-Ionic Surfactant Vesicles Loaded with Rifamycin S
by Verdiana Marchianò, Maria Matos, Ismael Marcet, Maria Paz Cabal, Gemma Gutiérrez and Maria Carmen Blanco-López
Pharmaceutics 2022, 14(12), 2626; https://doi.org/10.3390/pharmaceutics14122626 - 28 Nov 2022
Cited by 6 | Viewed by 2283
Abstract
These days, the eradication of bacterial infections is more difficult due to the mechanism of resistance that bacteria have developed towards traditional antibiotics. One of the medical strategies used against bacteria is the therapy with drug delivery systems. Non-ionic vesicles are nanomaterials with [...] Read more.
These days, the eradication of bacterial infections is more difficult due to the mechanism of resistance that bacteria have developed towards traditional antibiotics. One of the medical strategies used against bacteria is the therapy with drug delivery systems. Non-ionic vesicles are nanomaterials with good characteristics for encapsulating drugs, due to their bioavailability and biodegradability, which allow the drugs to reach the specific target and reduce their side effects. In this work, the antibiotic Rifamycin S was encapsulated. The rifamycin antibiotics family has been widely used against Mycobacterium tuberculosis, but recent studies have also shown that rifamycin S and rifampicin derivatives have bactericidal activity against Staphylococcus epidermidis and Staphylococcus aureus. In this work, a strain of S. aureus was selected to study the antimicrobial activity through Minimum Inhibitory Concentration (MIC) assay. Three formulations of niosomes were prepared using the thin film hydration method by varying the composition of the aqueous phase, which included MilliQ water, glycerol solution, or PEG400 solution. Niosomes with a rifamycin S concentration of 0.13 μg/g were satisfactorily prepared. Nanovesicles with larger size and higher encapsulation efficiency (EE) were obtained when using glycerol and PEG400 in the aqueous media. Our results showed that niosomes consisting of an aqueous glycerol solution have higher stability and EE across a diversity of temperatures and pHs, and a lower MIC of rifamycin S against S. aureus. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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17 pages, 5556 KiB  
Article
Exposure of the Basophilic Cell Line KU812 to Liposomes Reveals Activation Profiles Associated with Potential Anaphylactic Responses Linked to Physico-Chemical Characteristics
by Alexander J. Plant-Hately, Burcu Eryilmaz, Christopher A. W. David, Danielle E. Brain, Bethany J. Heaton, Yvonne Perrie and Neill J. Liptrott
Pharmaceutics 2022, 14(11), 2470; https://doi.org/10.3390/pharmaceutics14112470 - 15 Nov 2022
Cited by 5 | Viewed by 2719
Abstract
Lipidic nanoparticles (LNP), particularly liposomes, have been proven to be a successful and versatile platform for intracellular drug delivery for decades. Whilst primarily developed for small molecule delivery, liposomes have recently undergone a renaissance due to their success in vaccination strategies, delivering nucleic [...] Read more.
Lipidic nanoparticles (LNP), particularly liposomes, have been proven to be a successful and versatile platform for intracellular drug delivery for decades. Whilst primarily developed for small molecule delivery, liposomes have recently undergone a renaissance due to their success in vaccination strategies, delivering nucleic acids, in the COVID-19 pandemic. As such, liposomes are increasingly being investigated for the delivery of nucleic acids, beyond mRNA, as non-viral gene delivery vectors. Although not generally considered toxic, liposomes are increasingly shown to not be immunologically inert, which may have advantages in vaccine applications but may limit their use in other conditions where immunological responses may lead to adverse events, particularly those associated with complement activation. We sought to assess a small panel of liposomes varying in a number of physico-chemical characteristics associated with complement activation and inflammatory responses, and examine how basophil-like cells may respond to them. Basophils, as well as other cell types, are involved in the anaphylactic responses to liposomes but are difficult to isolate in sufficient numbers to conduct large scale analysis. Here, we report the use of the human KU812 cell line as a surrogate for primary basophils. Multiple phenotypic markers of activation were assessed, as well as the release of histamine and inflammasome activity within the cells. We found that larger liposomes were more likely to result in KU812 activation, and that non-PEGylated liposomes were potent stimulators of inflammasome activity (four-fold greater IL-1β secretion than untreated controls), and a lower ratio of cholesterol to lipid was also associated with greater IL-1β secretion ([Cholesterol:DSPC ratio] 1:10; 0.35 pg/mL IL-1β vs. 5:10; 0.1 pg/mL). Additionally, PEGylation appeared to be associated with direct KU812 activation. These results suggest possible mechanisms related to the consequences of complement activation that may be underpinned by basophilic cells, in addition to other immune cell types. Investigation of the mechanisms behind these responses, and their impact on use in vivo, are now warranted. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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22 pages, 3888 KiB  
Article
Amidated Pluronic Decorated Muco-Penetrating Self-Nano Emulsifying Drug Delivery System (SNEDDS) for Improved Anti-Salmonella typhi Potential
by Rabia Arshad, Muhammad Salman Arshad, Tanveer A. Tabish, Syed Nisar Hussain Shah, Saira Afzal and Gul Shahnaz
Pharmaceutics 2022, 14(11), 2433; https://doi.org/10.3390/pharmaceutics14112433 - 10 Nov 2022
Cited by 11 | Viewed by 3076
Abstract
The enteric system residing notorious Salmonella typhimurium (S. typhi) is an intracellular, food-borne, and zoonotic pathogen causing typhoid fever. Typhoid fever is one of the leading causes of mortality and morbidity in developing and underdeveloped countries. It also increased the prevalence [...] Read more.
The enteric system residing notorious Salmonella typhimurium (S. typhi) is an intracellular, food-borne, and zoonotic pathogen causing typhoid fever. Typhoid fever is one of the leading causes of mortality and morbidity in developing and underdeveloped countries. It also increased the prevalence of multidrug resistance globally. Currently, available anti-bacterial modalities are unable to penetrate into the intracellular compartments effectively for eradicating S. typhi infection. Therefore, in this study, we developed nanostructured lipid-based carriers in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for targeted delivery of ciprofloxacin (CIP) into the S. typhi intracellular reservoirs. Capryol 90, Tween 80, and Span 20 were finalized as suitable oil, surfactant, and co-surfactant, respectively, according to the pseudoternary phase diagram emulsifying region. Targeting capability and mucopenetration of the SNEDDS was attributed to the inclusion of amidated pluronic (NH2-F127). Developed NH2-F127 SNEDDS were characterized via physicochemical, in vitro, ex vivo, and in vivo evaluation parameters. The size of the SNEDDS was found to be 250 nm, having positively charged zeta potential. In vitro dissolution of SNEDDS showed 80% sustained release of CIP in 72 h with maximum entrapment efficiency up to 90% as well as good hemocompatibility by showing less than 0.2% hemolysis and 90% biocompatibility. The survival rate of S. typhi in macrophages (RAW 264.7) was minimal, i.e., only 2% in the case of NH2-F127 SNEDDS. Macrophage uptake assay via nanostructures confirmed the maximum cellular uptake as evidenced by the highest fluorescence. Biofilm dispersion assay showed rapid eradication of developed resistant biofilms on the gall bladder. In vivo pharmacokinetics showed improved bioavailability by showing an increased area under the curve (AUC) value. Taken together, NH2-F127-SNEDDS can be utilized as an alternative and efficient delivery system for the sustained release of therapeutic amounts of CIP for the treatment of S. typhi. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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22 pages, 3455 KiB  
Article
Augmented Oral Bioavailability and Prokinetic Activity of Levosulpiride Delivered in Nanostructured Lipid Carriers
by Sadia Tabassam Arif, Shahiq uz Zaman, Muhammad Ayub Khan, Tanveer A. Tabish, Muhammad Farhan Sohail, Rabia Arshad, Jin-Ki Kim and Alam Zeb
Pharmaceutics 2022, 14(11), 2347; https://doi.org/10.3390/pharmaceutics14112347 - 31 Oct 2022
Cited by 6 | Viewed by 3050
Abstract
The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared [...] Read more.
The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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Review

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23 pages, 410 KiB  
Review
Recent Advances in Cell Membrane Coated-Nanoparticles as Drug Delivery Systems for Tackling Urological Diseases
by Cenchao Yao, Dahong Zhang, Heng Wang and Pu Zhang
Pharmaceutics 2023, 15(7), 1899; https://doi.org/10.3390/pharmaceutics15071899 - 6 Jul 2023
Cited by 14 | Viewed by 4541
Abstract
Recent studies have revealed the functional roles of cell membrane coated-nanoparticles (CMNPs) in tackling urological diseases, including cancers, inflammation, and acute kidney injury. Cells are a fundamental part of pathology to regulate nearly all urological diseases, and, therefore, naturally derived cell membranes inherit [...] Read more.
Recent studies have revealed the functional roles of cell membrane coated-nanoparticles (CMNPs) in tackling urological diseases, including cancers, inflammation, and acute kidney injury. Cells are a fundamental part of pathology to regulate nearly all urological diseases, and, therefore, naturally derived cell membranes inherit the functional role to enhance the biopharmaceutical performance of their encapsulated nanoparticles on drug delivery. In this review, methods for CMNP synthesis and surface engineering are summarized. The application of different types of CMNPs for tackling urological diseases is updated, including cancer cell membrane, stem cell membrane, immune cell membrane, erythrocytes cell membranes, and extracellular vesicles, and their potential for clinical use is discussed. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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34 pages, 3221 KiB  
Review
Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review
by Cláudia Viegas, Ana B. Patrício, João M. Prata, Akhtar Nadhman, Pavan Kumar Chintamaneni and Pedro Fonte
Pharmaceutics 2023, 15(6), 1593; https://doi.org/10.3390/pharmaceutics15061593 - 25 May 2023
Cited by 146 | Viewed by 15052
Abstract
Solid–lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in [...] Read more.
Solid–lipid nanoparticles and nanostructured lipid carriers are delivery systems for the delivery of drugs and other bioactives used in diagnosis, therapy, and treatment procedures. These nanocarriers may enhance the solubility and permeability of drugs, increase their bioavailability, and extend the residence time in the body, combining low toxicity with a targeted delivery. Nanostructured lipid carriers are the second generation of lipid nanoparticles differing from solid lipid nanoparticles in their composition matrix. The use of a liquid lipid together with a solid lipid in nanostructured lipid carrier allows it to load a higher amount of drug, enhance drug release properties, and increase its stability. Therefore, a direct comparison between solid lipid nanoparticles and nanostructured lipid carriers is needed. This review aims to describe solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems, comparing both, while systematically elucidating their production methodologies, physicochemical characterization, and in vitro and in vivo performance. In addition, the toxicity concerns of these systems are focused on. Full article
(This article belongs to the Special Issue Nanostructured Lipid Carriers: Design, Properties and Applications in Drug Delivery)
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