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Pharmaceutics
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Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery...
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Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications

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

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 9346

Special Issue Editor

Dr. Evgenia Mitsou

E-Mail Website
Guest Editor
Department of Molecular Chemistry and Materials Science, Weizmann Institute of Science, 76100 Rehovot, Israel
Interests: nanomedicine; micro/nanoemulsions; liposomes; lipid nanoparticles; polymer-functionalized nanoformulations; gels; physicochemical characterization; electron paramagnetic resonance

Special Issue Information

Dear Colleagues,

We are delighted to present this Special Issue dedicated to microemulsions and nanoemulsions designed for precision in pharmaceutical applications. In the rapidly growing field of nanomedicine, these colloidal nanocarriers and related systems, such as micro/nanoemulsion-based gels and nanocapsules, are standout contributors. They offer significant advantages for biomedical applications because they can encapsulate compounds of different polarity while demonstrating stability coupled with ease of preparation. Micro- and nanoemulsions can deliver a wide range of molecules, including drugs, enzymes, imaging agents, and even nucleic acids, while enhancing their efficiency. Unique design approaches enable their penetration into targeted tissues and facilitate controlled release at the nanoscale upon different administration routes. In response to the demand for more effective and personalized treatments, surface functionalization with polymers, peptides, and antibodies emerges as a crucial strategy that further enhances precision, increased bioavailability, prolonged drug release, and enhanced patient compliance.

This Special Issue in Pharmaceutics highlights recent breakthroughs in microemulsions, nanoemulsions, and related systems in nanomedicine, with special focus on the targeted delivery of molecules alongside advancements in diagnosis and theranostics. Our goal is to build a well-balanced collection, including research articles and reviews, that will elucidate the critical role of these systems in pharmaceutical research, from their physicochemical characterization to their biological evaluation; this involves not only highlighting the latest progress but also outlining the future trajectory of this dynamic field.

We look forward to receiving your contributions.

Dr. Evgenia Mitsou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

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

  • nanoemulsions
  • microemulsions
  • micro/nanoemulsion-related systems
  • stimuli responsive micro/nanoemulsions
  • targeted drug delivery
  • surface functionalization
  • controlled release
  • diagnostics
  • theranostics

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Published Papers (5 papers)

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Research

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18 pages, 1159 KiB  
Article
Parenteral Nanoemulsion for Optimized Delivery of GL-II-73 to the Brain—Comparative In Vitro Blood–Brain Barrier and In Vivo Neuropharmacokinetic Evaluation
by Kristina Jezdić, Jelena Đoković, Ivan Jančić, Tanja Ilić, Biljana Bufan, Bojan Marković, Jana Ivanović, Tijana Stanković, Nebojša D. Cekić, Vassiliki Papadimitriou, Dishary Sharmin, Prithu Mondal, James M. Cook, Snežana D. Savić and Miroslav M. Savić
Pharmaceutics 2025, 17(3), 354; https://doi.org/10.3390/pharmaceutics17030354 - 10 Mar 2025
Viewed by 829
Abstract
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired. Our aim was to develop an optimized nanoemulsion containing GL-II-73 [...] Read more.
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired. Our aim was to develop an optimized nanoemulsion containing GL-II-73 and subsequently test whether this would improve permeation across the blood–brain barrier (BBB) and availability in the brain. Methods: The nanoemulsions were formulated and subjected to detailed physiochemical characterization. The optimized formulation was tested in comparison to a solution of GL-II-73 in the appropriate solvent in an in vitro model of the blood–brain barrier based on human induced pluripotent stem cell-derived microvascular endothelial cells, astrocytes, and pericytes. Plasma and brain exposure to GL-II-73 and its metabolite MP-III-022 was investigated in an in vivo neuropharmacokinetic study in rats exposed to the selected nanoemulsion and the conventional solution formulation. Results: The selected biocompatible nanoemulsion exhibited satisfactory physicochemical properties for parenteral administration, with a Z-ave of 122.0 ± 1.5, PDI of 0.123 ± 0.009 and zeta potential of −40.7 ± 1.5, pH of 5.16 ± 0.04, and adequate stability after one year of storage, and allowed the localization of GL-II-73 in the stabilization layer. The permeability of GL-II-73 through the BBB was twice as high with the selected nanoemulsion as with the solution. The availability of GL-II-73 and MP-III-022 (also a positive allosteric modulator selective for α5GABAA receptors) in the brain was 24% and 61% higher, respectively, after intraperitoneal administration of the nanoemulsion compared to the solution; the former increase was statistically significant. Conclusions: The increased permeability in vitro proved to be a good predictor for the improved availability of GL-II-73 in brain tissue in vivo from the formulation obtained by encapsulation in a nanoemulsion. The putative additive effect of the parent molecule and its metabolite MP-III-022 could lead to enhanced and/or prolonged modulation of α5GABAA receptors in the brain. Full article
(This article belongs to the Special Issue Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications)
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21 pages, 2256 KiB  
Article
Development and Characterization of a Microemulsion Containing a Cannabidiol Oil and a Hydrophilic Extract from Sambucus ebulus for Topical Administration
by Teresa Areses-Huete, Damian Cordoba-Diaz, Ana Isabel Torres-Suárez and Manuel Cordoba-Diaz
Pharmaceutics 2024, 16(6), 705; https://doi.org/10.3390/pharmaceutics16060705 - 24 May 2024
Viewed by 1603
Abstract
Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a [...] Read more.
Cannabidiol (CBD) is a safe and non-psychotropic phytocannabinoid with a wide range of potential therapeutic anti-inflamatory and antioxidant activities. Due to its lipophilicity, it is normally available dissolved in oily phases. The main aim of this work was to develop and characterize a new formulation of a microemulsion with potential anti-inflammatory and antioxidant activity for the topical treatment of inflammatory skin disorders. The microemulsion system was composed of a 20% CBD oil, which served as the hydrophobic phase; Labrasol/Plurol Oleique (1:1), which served as surfactant and cosurfactant (S/CoS), respectively; and an aqueous vegetal extract obtained from Sambucus ebulus L. (S. ebulus) ripe fruits, which has potential anti-oxidant and anti-inflammatory activity and which served as the aqueous phase. A pseudo-ternary phase diagram was generated, leading to the selection of an optimal proportion of 62% (S/CoS), 27% CBD oil and 11% water and, after its reproducibility was tested, the aqueous phases were replaced by the vegetal hydrophilic extract. The defined systems were characterized in terms of conductivity, droplet size (by laser scattering), compatibility of components (by differential scanning calorimetry) and rheological properties (using a rotational rheometer). The designed microemulsion showed good stability and slight pseudo-plastic behavior. The release properties of CBD from the oil phase and caffeic acid from the aqueous phase of the microemulsion were studied via in vitro diffusion experiments using flow-through diffusion cells and were compared to those of a CBD oil and a microemulsion containing only CBD as an active substance. It was found that the inclusion of the original oil in microemulsions did not result in a significant modification of the release of CBD, suggesting the possibility of including hydrophilic active compounds in the formulation and establishing an interesting strategy for the development of future formulations. Full article
(This article belongs to the Special Issue Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications)
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23 pages, 4266 KiB  
Article
Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin
by Nontachai Magrode, Worrapan Poomanee, Kanokwan Kiattisin and Chadarat Ampasavate
Pharmaceutics 2024, 16(4), 554; https://doi.org/10.3390/pharmaceutics16040554 - 19 Apr 2024
Cited by 7 | Viewed by 2328
Abstract
The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified [...] Read more.
The targeted delivery of a hydrophilic Tripeptide-3 to the skin using microemulsions or nanoemulsions for facial oil reduction was the focus of this study. The impact factors affecting oil/water transparent dispersion formation, such as the surfactant system, HLB value, and co-solvent, were identified through the water titration method and pseudoternary phase diagram plots. The interfacial tension between caprylic/capric triglyceride (CCT oil) and water was significantly reduced by the surfactant/co-surfactant combination (Smix) of Cremophore® RH40 and a double-tails co-surfactant, polyglycerol-3-diisostearate, at an HLB of 13 together with a water-to-co-solvent (PG) ratio of 1:1. A two-level full factorial design of experiment (FFD-DoE) emphasized the independent variables of the HLB value, co-solvent, and CCT oil contents affecting the optimal compositions for micro- or nanoemulsion formation. The low-energy spontaneous emulsification of the optimized combination at a low Smix content (10%) yielded the translucent oil-in-water Tripeptide-3 nanoemulsions with an internal droplet size of 25.7 ± 1.20 nm, a narrow polydispersity index of 0.237 ± 0.129, and 70.6 ± 0.58% transmittance. The in vitro skin permeation study revealed a significantly higher skin penetration and retention of the Tripeptide-3 nanoemulsions compared to the high surfactant microemulsions and coarse emulsions. Skin irritation and oil control efficacy were evaluated in healthy volunteers before and after product application for 28 days. The obtained nanoemulsions not only decreased sebum production but also enhanced skin moisture levels. In conclusion, the meticulously designed nanoemulsions, incorporating suitable excipients, show a promising delivery system for hydrophilic peptides to control sebum overproduction in oily facial skin. Full article
(This article belongs to the Special Issue Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications)
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14 pages, 1427 KiB  
Article
Chemical Characterization, Leishmanicidal Activity and In Vitro Cytotoxicity of the Essential Oil Extracted from Pectis brevipedunculata (Gardner) Sch.Bip. and Its Incorporation into Microemulsion Systems
by Auxiliadora Cristina Correa Barata Lopes, Jessyane Rodrigues do Nascimento, Marcos Bispo Pinheiro Camara, Aldilene da Silva Lima, Gláucia Laís Nunes Lopes, Matheus Oliveira do Nascimento, Júlia Karla Albuquerque Melo Xavier, Caroline Martins de Jesus, Cáritas de Jesus Silva Mendonça, André Luis Menezes Carvalho, Lucilene Amorim Silva and Cláudia Quintino da Rocha
Pharmaceutics 2024, 16(1), 87; https://doi.org/10.3390/pharmaceutics16010087 - 9 Jan 2024
Cited by 3 | Viewed by 2368
Abstract
Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The [...] Read more.
Pectis brevipedunculata (Gardner) Sch.Bip., known in Brazil as alecrim do campo, is a small Asteraceae family plant with a calming effect and consumed as tea. This species contains components, such as neral and geranial, that display various biological activities, such as leishmanicidal. The aim was to chemically characterize the essential oil (EO) obtained from P. brevipedunculata (EO-PB) by hydrodistillation and a microemulsion formulated with EO (ME-PB), Tween 80 and Transcutol P, assess the leishmanicidal effect against Leishmania (L.) amazonensis promastigotes and cytotoxicity against RAW 264.7. EO-PB and ME-PB were analyzed by Gas Chromatography Mass Spectrometry (GC/MS). Monoterpene hydrocarbons were noteworthy among the identified compounds. The main EO-PB constituents were α-pinene and limonene, followed by neral and geranial, which were maintained in ME-PB. EO-PB presented an inhibitory concentration (IC50) of 20 µg/mL and ME-PB of 0.93 µg/mL. ME-PB inhibition towards the parasite was 20-fold higher than that of EO-PB. This indicated that EO incorporation to the microemulsion resulted in optimized biological activity. Selectivity indices indicate that ME-PB is more selective concerning parasite inhibition. Thus, ME-PB may comprise an adequate approach against Leishmania, as the inhibitory concentration (IC50) promastigotes was lower than that considered toxic for cells cell cytotoxicity of 50% (CC50). Full article
(This article belongs to the Special Issue Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications)
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Review

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35 pages, 3902 KiB  
Review
Advancements in Nanoemulsion-Based Drug Delivery Across Different Administration Routes
by Maria D. Chatzidaki and Evgenia Mitsou
Pharmaceutics 2025, 17(3), 337; https://doi.org/10.3390/pharmaceutics17030337 - 5 Mar 2025
Viewed by 1254
Abstract
Nanoemulsions (NEs) have emerged as effective drug delivery systems over the past few decades due to their multifaceted nature, offering advantages such as enhanced bioavailability, protection of encapsulated compounds, and low toxicity. In the present review, we focus on advancements in drug delivery [...] Read more.
Nanoemulsions (NEs) have emerged as effective drug delivery systems over the past few decades due to their multifaceted nature, offering advantages such as enhanced bioavailability, protection of encapsulated compounds, and low toxicity. In the present review, we focus on advancements in drug delivery over the last five years across (trans)dermal, oral, ocular, nasal, and intra-articular administration routes using NEs. Rational selection of components, surface functionalization, incorporation of permeation enhancers, and functionalization with targeting moieties are explored for each route discussed. Additionally, apart from NEs, we explore NE-based drug delivery systems (e.g., NE-based gels) while highlighting emerging approaches such as vaccination and theranostic applications. The growing interest in NEs for drug delivery purposes is reflected in clinical trials, which are also discussed. By summarizing the latest advances, exploring new strategies, and identifying critical challenges, this review focuses on developments for efficient NE-based therapeutic approaches. Full article
(This article belongs to the Special Issue Micro- and Nanoemulsions in Therapeutics: Advancements in Targeted Drug Delivery and Theranostic Applications)
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