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Pharmaceutics
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Lipid-Based Dispersed Systems for Drug Delivery
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Lipid-Based Dispersed Systems for 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 (20 March 2022) | Viewed by 25233

Special Issue Editor

Prof. Dr. Eryvaldo Sócrates Tabosa Do Egito

E-Mail Website
Guest Editor
Pharmacy Department, Universidade Federal do Rio Grande do Norte, Natal 59012-570, Brazil
Interests: drug delivery; nanotechnology; emulsions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last years, technology applied to therapeutics has been extensively used in order to provide feasible alternatives to the use of burdensome, but extremely effective, molecules. Highly lipophilic compounds have challenged researchers in the academia and in the industry to develop formulations that can overcome drawbacks such as drug content, poor bioavailability, instability, toxicity and several others. Hence, lipid-based dispersed systems, based on synthetic or natural oils, are advantageous alternatives to drug delivery. This special issue is dedicated to publish innovative and relevant research in the field of development, characterization, stability and biological activity evaluation of lipid-based dispersed systems. Among such complex systems, the special issue will consider, but not limit its range to, micelles, emulsions, nanoemulsions, microemulsions, micro and nanocapsules, solid lipid nanoparticles, liposomes and other vesicles.

Prof. Dr. Eryvaldo Sócrates Tabosa Egito
Guest Editor

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Keywords

  • nanostructured lipid nanocarrier
  • microemulsion
  • nanoemulsion
  • nanoparticle
  • liposome

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Published Papers (7 papers)

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Research

16 pages, 2450 KiB  
Article
Safety and Prophylactic Efficacy of Liposome-Based Vaccine against the Drug-Resistant Acinetobacter baumannii in Mice
by Masood Alam Khan, Khaled S. Allemailem, Hamzah Maswadeh and Hina Younus
Pharmaceutics 2022, 14(7), 1357; https://doi.org/10.3390/pharmaceutics14071357 - 27 Jun 2022
Cited by 6 | Viewed by 2231
Abstract
In recent years, the emergence of multidrug-resistant Acientobacter baumannii has greatly threatened public health and depleted our currently available antibacterial armory. Due to limited therapeutic options, the development of an effective vaccine formulation becomes critical in order to fight this drug-resistant pathogen. The [...] Read more.
In recent years, the emergence of multidrug-resistant Acientobacter baumannii has greatly threatened public health and depleted our currently available antibacterial armory. Due to limited therapeutic options, the development of an effective vaccine formulation becomes critical in order to fight this drug-resistant pathogen. The objective of the present study was to develop a safe vaccine formulation that can be effective against A. baumannii infection and its associated complications. Here, we prepared liposomes-encapsulated whole cell antigens (Lip-WCAgs) as a vaccine formulation and investigated its prophylactic efficacy against the systemic infection of A. baumannii. The immunization with Lip-WCAgs induced the higher production of antigen-specific antibody titers, greater lymphocyte proliferation, and increased secretion of Th1 cytokines, particularly IFN-γ and IL-12. Antisera from Lip-WCAgs-immunized mice showed the utmost bactericidal activity and potently inhibited the biofilm formation by A. baumannii. Interestingly, Lip-WCAgs-induced immune response was translated in in vivo protection studies as the immunized mice exhibited the highest resistance to A. baumannii infection. Mice in the group immunized with Lip-WCAgs had an 80% survival rate and a bacterial burden of 5464 ± 1193 CFUs per gram of the lung tissue, whereas the mice immunized with IFA-WCAgs had a 50% survival rate and 51,521 ± 8066 CFUs. In addition, Lip-WCAgs vaccinated mice had lower levels of the inflammatory markers, including CRP, IL-6, IL-1β, and TNF-α. The findings of this study suggest that Lip-WCAgs may be considered a potential vaccine formulation to protect individuals against A. baumannii infection. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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13 pages, 1892 KiB  
Article
Oleic Acid-Based Self Micro-Emulsifying Delivery System for Enhancing Antifungal Activities of Clotrimazole
by Ting-Lun Yang, Chien-Ming Hsieh, Ling-Jei Meng, Tsuimin Tsai and Chin-Tin Chen
Pharmaceutics 2022, 14(3), 478; https://doi.org/10.3390/pharmaceutics14030478 - 22 Feb 2022
Cited by 12 | Viewed by 2820
Abstract
Due to the increasing rate of drug resistance in Candida spp., higher doses of antifungal agents are being used resulting in toxicity. Drug delivery systems have been shown to provide an effective approach to enhance the efficacy and reduce the toxicity of antifungal [...] Read more.
Due to the increasing rate of drug resistance in Candida spp., higher doses of antifungal agents are being used resulting in toxicity. Drug delivery systems have been shown to provide an effective approach to enhance the efficacy and reduce the toxicity of antifungal agents. Oleic acid was revealed to effectively inhibit biofilm formation, hence reducing the virulence of Candida albicans. In this study, oleic acid-based self micro-emulsifying delivery systems (OA-SMEDDS) were developed for delivering clotrimazole (CLT). Based on the pseudo-ternary phase diagram and loading capacity test, the optimal ratio of OA-SMEDDS with CLT was selected. CLT-loaded OA-SMEDDS not only bears a higher drug loading capacity but also maintains good storage stability. The minimum inhibitory concentration (MIC50) of CLT-loaded OA-SMEDDS (0.01 μg/mL) in Candida albicans was significantly lower than that of CLT dissolved in DMSO (0.04 μg/mL). Moreover, we showed CLT-loaded OA-SMEDDS could effectively prevent biofilm formation and destroy the intact biofilm structure of Candida albicans. Furthermore, a CLT-loaded OA-SMEDDS gel was developed and evaluated for its antifungal properties. Disk diffusion assay indicated that both CLT-loaded OA-SMEDDS and CLT-loaded OA-SMEDDS gels were more effective than commercially available products in inhibiting the wild-type and drug-resistant species of Candida. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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15 pages, 3164 KiB  
Article
Green Nanoemulsion Stabilized by In Situ Self-Assembled Natural Oil/Native Cyclodextrin Complexes: An Eco-Friendly Approach for Enhancing Anticancer Activity of Costunolide against Lung Cancer Cells
by Nabil A. Alhakamy, Shaimaa M. Badr-Eldin, Osama A. A. Ahmed, Hibah M. Aldawsari, Solomon Z. Okbazghi, Mohamed A. Alfaleh, Wesam H. Abdulaal, Thikryat Neamatallah, Omar D. Al-hejaili and Usama A. Fahmy
Pharmaceutics 2022, 14(2), 227; https://doi.org/10.3390/pharmaceutics14020227 - 19 Jan 2022
Cited by 10 | Viewed by 2351
Abstract
Lung cancer is the second-most deadly malignancy worldwide, of which smoking is considered a major risk factor and causes 75–80% of lung cancer-related deaths. Costunolide (CTD) extracted from plant species Saussurea, Aucklandia, and Inula exhibits potent anticancer properties, specifically in lung cancer and [...] Read more.
Lung cancer is the second-most deadly malignancy worldwide, of which smoking is considered a major risk factor and causes 75–80% of lung cancer-related deaths. Costunolide (CTD) extracted from plant species Saussurea, Aucklandia, and Inula exhibits potent anticancer properties, specifically in lung cancer and leukemia. Several nanoemulsions were prepared and optimized using a three-factor Box–Behnken experimental design. The optimized green nanoemulsion (GNE) showed a vesicle size of 199.56 nm. The IC50 values revealed that A549 cells were significantly more sensitive to the optimized CTD formula than the plain formula and raw CTD. A cell cycle analysis revealed that the optimized CTD formula treatment resulted in significant cell cycle arrest at the S phase. The results also indicated that treatment with the CTD formula significantly increased caspase-3, Bax, Bcl-2, and p53 mRNA expression compared to the plain formula and CTD raw. In terms of the inflammatory markers, the optimized formula significantly reduced the activity of TNF-α and NF-κB in comparison with the plain formula and raw drug only. Overall, the findings from the study proved that a CTD GNE formulation could be a promising therapeutic approach for the treatment of lung cancer. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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12 pages, 1671 KiB  
Article
Endocytic Uptake of Solid Lipid Nanoparticles by the Nasal Mucosa
by Ammar S. Al Khafaji and Maureen D. Donovan
Pharmaceutics 2021, 13(5), 761; https://doi.org/10.3390/pharmaceutics13050761 - 20 May 2021
Cited by 13 | Viewed by 3332
Abstract
Nanoparticles may provide unique therapeutic opportunities when administered via the nasal cavity, yet the primary uptake and transfer pathways for these particles within the nasal mucosa are not well understood. The endocytic pathways involved in the uptake of fluorescently labeled, (Nile Red) solid [...] Read more.
Nanoparticles may provide unique therapeutic opportunities when administered via the nasal cavity, yet the primary uptake and transfer pathways for these particles within the nasal mucosa are not well understood. The endocytic pathways involved in the uptake of fluorescently labeled, (Nile Red) solid lipid nanoparticles (SLNs) of different sizes (~30, 60, and 150 nm) were studied using excised bovine olfactory and nasal respiratory tissues. Endocytic activity contributing to nanoparticle uptake was investigated using a variety of pharmacological inhibitors, but none of the inhibitors were able to completely eliminate the uptake of the SLNs. The continued uptake of nanoparticles following exposure to individual inhibitors suggests that a number of endocytic pathways work in combination to transfer nanoparticles into the nasal mucosa. Following exposure to the general metabolic inhibitors, 2,4-DNP and sodium azide, additional, non-energy-dependent pathways for nanoparticle uptake were also observed. While the smallest nanoparticles (30 nm) were the most resistant to the effects of pharmacologic inhibitors, the largest (150 nm) were still able to transfer significant amounts of the particles into the tissues. The rapid nanoparticle uptake observed demonstrates that these lipid particles are promising vehicles to accomplish both local and systemic drug delivery following nasal administration. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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17 pages, 5505 KiB  
Article
Ferri–Liposomes: Preformulation and Selective Cytotoxicity against A549 Lung Cancer Cells
by Marina Guedes Fonseca de Souza, Fabrícia Nunes de Jesus Guedes, Marli Luiza Tebaldi, Éverton do Nascimento Alencar, Lucas Amaral-Machado, Eryvaldo Sócrates Tabosa do Egito, André Luis Branco de Barros and Daniel Crístian Ferreira Soares
Pharmaceutics 2021, 13(5), 712; https://doi.org/10.3390/pharmaceutics13050712 - 13 May 2021
Cited by 14 | Viewed by 3156
Abstract
Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung [...] Read more.
Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri–liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri–liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri–liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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16 pages, 13699 KiB  
Article
Combined Self-Nanoemulsifying and Solid Dispersion Systems Showed Enhanced Cinnarizine Release in Hypochlorhydria/Achlorhydria Dissolution Model
by Ahmad A. Shahba, Ahmad Y. Tashish, Fars K. Alanazi and Mohsin Kazi
Pharmaceutics 2021, 13(5), 627; https://doi.org/10.3390/pharmaceutics13050627 - 28 Apr 2021
Cited by 18 | Viewed by 2500
Abstract
The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 [...] Read more.
The study aims to design a novel combination of drug-free solid self-nanoemulsifying drug delivery systems (S-SNEDDS) + solid dispersion (SD) to enhance cinnarizine (CN) dissolution at high pH environment caused by hypochlorhydria/achlorhydria. Drug-loaded and drug-free liquid SNEDDS were solidified using Neusilin® US2 at 1:1 and 1:2 ratios. Various CN-SDs were prepared using freeze drying and microwave technologies. The developed SDs were characterized by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD). In-vitro dissolution studies were conducted to evaluate CN formulations at pH 6.8. Drug-free S-SNEDDSs showed acceptable self-emulsification and powder flow properties. DSC and XRD showed that CN was successfully amorphized into SDs. The combination of drug-free S-SNEDDS + pure CN showed negligible drug dissolution due to poor CN migration into the formed nanoemulsion droplets. CN-SDs and drug-loaded S-SNEDDS showed only 4% and 23% dissolution efficiency (DE) while (drug-free S-SNEDDS + FD-SD) combination showed 880% and 160% enhancement of total drug release compared to uncombined SD and drug-loaded S-SNEDDS, respectively. (Drug-free S-SNEDDS + SD) combination offer a potential approach to overcome the negative impact of hypochlorhydria/achlorhydria on drug absorption by enhancing dissolution at elevated pH environments. In addition, the systems minimize the adverse effect of adsorbent on drug release. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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20 pages, 3397 KiB  
Article
Novel Gel Microemulsion as Topical Drug Delivery System for Curcumin in Dermatocosmetics
by Cristina Scomoroscenco, Mircea Teodorescu, Adina Raducan, Miruna Stan, Sorina Nicoleta Voicu, Bodgan Trica, Claudia Mihaela Ninciuleanu, Cristina Lavinia Nistor, Catalin Ionut Mihaescu, Cristian Petcu and Ludmila Otilia Cinteza
Pharmaceutics 2021, 13(4), 505; https://doi.org/10.3390/pharmaceutics13040505 - 7 Apr 2021
Cited by 50 | Viewed by 7417
Abstract
Gel microemulsion combines the advantages of the microemulsion, which can encapsulate, protect and deliver large quantities of active ingredients, and the gel, which is so appreciated in the cosmetic industry. This study aimed to develop and characterize new gel microemulsions suitable for topical [...] Read more.
Gel microemulsion combines the advantages of the microemulsion, which can encapsulate, protect and deliver large quantities of active ingredients, and the gel, which is so appreciated in the cosmetic industry. This study aimed to develop and characterize new gel microemulsions suitable for topical cosmetic applications, using grape seed oil as the oily phase, which is often employed in pharmaceuticals, especially in cosmetics. The optimized microemulsion was formulated using Tween 80 and Plurol® Diisostearique CG as a surfactant mix and ethanol as a co-solvent. Three different water-soluble polymers were selected in order to increase the viscosity of the microemulsion: Carbopol® 980 NF, chitosan, and sodium hyaluronate salt. All used ingredients are safe, biocompatible and biodegradable. Curcumin was chosen as a model drug. The obtained systems were physico-chemically characterized by means of electrical conductivity, dynamic light scattering, polarized microscopy and rheometric measurements. Evaluation of the cytotoxicity was accomplished by MTT assay. In the final phase of the study, the release behavior of Curcumin from the optimized microemulsion and two gel microemulsions was evaluated. Additionally, mathematical models were applied to establish the kinetic release mechanism. The obtained gel microemulsions could be effective systems for incorporation and controlled release of the hydrophobic active ingredients. Full article
(This article belongs to the Special Issue Lipid-Based Dispersed Systems for Drug Delivery)
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