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Pharmaceutics
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Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation,...
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Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition

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

Deadline for manuscript submissions: 30 September 2026 | Viewed by 4748

Editors

Prof. Dr. Denitsa Momekova

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Guest Editor
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria
Interests: pharmaceutical nanotechnology; nanosized drug delivery carriers; nanovesicles; targeted drug and gene delivery; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals
Dr. Velichka Andonova

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Guest Editor
Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: emulsion polymerization; drug stability; pharmaceutical nanotechnology; pharmaceutical research and development; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals
Dr. Viliana Eduardova Gugleva

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Guest Editor
Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: vesicular systems; niosomes; stimuli-sensitive nanocarriers; inorganic nanoparticles
Special Issues, Collections and Topics in MDPI journals
Dr. Nadezhda Ivanova

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Guest Editor
Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 9000 Varna, Bulgaria
Interests: drug stability; silver nanoparticles; polymeric nanoparticles; pharmaceutical analysis; transdermal and mucosal drug permeation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lipid-based nanoparticulate drug delivery systems (i.e., liposomes, nanostructured lipid carriers, solid lipid nanoparticles, niosomes) have captured significant attention at both preclinical and clinical levels due to their advantageous characteristics, including biocompatibility, safety, and scale-up feasibility, as well as their promising biopharmaceutical performance and therapeutic outcomes. Lipid-based nanosystems are suitable carriers of various types of cargo—drugs, phytoconstituents, nucleic acids, and monoclonal antibodies—and are capable of improving their unfavorable physicochemical/pharmacokinetic characteristics and stability issues. These nanoscale systems exhibit the potential to enhance drug bioavailability, to provide a controlled release profile, and to achieve targeted delivery via suitable surface tailoring by tuning their physicochemical characteristics at the (pre)formulation stage.

This Special Issue aims to summarize recent advances in lipid-based nanoparticulate drug delivery systems and to highlight the future directions in this research area. Submissions of original research and review articles demonstrating progress in the field are welcome.

We express our appreciation to the authors of all submitted manuscripts for choosing this Special Issue to share their achievements. We are excited about the 2nd Edition, which is now open for the submission of high-quality manuscripts in the fields of nanomedicine, biomedicine, and advanced drug delivery.

Prof. Dr. Denitsa Momekova
Dr. Velichka Andonova
Dr. Viliana Eduardova Gugleva
Dr. Nadezhda Ivanova
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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

  • liposomes
  • nanoemulsions
  • nanostructured lipid carriers
  • niosomes
  • solid lipid nanoparticles
  • targeted drug delivery

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Related Special Issue

Published Papers (4 papers)

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Research

20 pages, 2957 KB  
Article
Nanostructured Lipid Carriers Enhance Ciprofloxacin Antibacterial Activity Through Diffusion-Controlled Release and Modulation of Bacterial Growth Kinetics
by Javiera Carrasco-Rojas, Felipe I. Sandoval, Javiera Solas-Soto, Christina M. A. P. Schuh, Lorena Rubio-Quiroz, Carlos F. Lagos, Francisco Arriagada and Andrea C. Ortiz
Pharmaceutics 2026, 18(4), 496; https://doi.org/10.3390/pharmaceutics18040496 - 17 Apr 2026
Viewed by 437
Abstract
Background: The increasing prevalence of multidrug-resistant bacterial infections highlights the need for drug-delivery strategies that improve antimicrobial exposure and sustain therapeutic activity. In this study, ciprofloxacin-loaded nanostructured lipid carriers (NLC-CIP) were developed and evaluated to better understand how formulation-dependent release behavior influences antibacterial [...] Read more.
Background: The increasing prevalence of multidrug-resistant bacterial infections highlights the need for drug-delivery strategies that improve antimicrobial exposure and sustain therapeutic activity. In this study, ciprofloxacin-loaded nanostructured lipid carriers (NLC-CIP) were developed and evaluated to better understand how formulation-dependent release behavior influences antibacterial performance against Escherichia coli. Methods: NLC-CIP were prepared and characterized in terms of size, polydispersity, encapsulation efficiency, and colloidal stability. In vitro release profiles were evaluated across different pH conditions, followed by kinetic modeling. Stability under refrigerated storage was assessed. Antibacterial performance was determined through IC50 measurements and dynamic growth-kinetic analyses, while cytotoxicity was evaluated in HepG2 cells. Results: Ciprofloxacin incorporation increased hydrodynamic diameter (~116 to 194 nm) while preserving low polydispersity (PdI~0.04), high colloidal stability, and encapsulation efficiency (96%). Release studies showed medium-dependent behavior, with rapid release at pH 1.2, 4.5, and 7.4, and more sustained profile at pH 6.8, consistent with diffusion-controlled kinetics (Weibull model). Refrigerated storage preserved release profiles while slowing early-stage kinetics. NLC-CIP showed improved apparent antibacterial activity, reducing the IC50 from 4.9 to 1.2 ng/mL, and sustained bacterial suppression by decreasing growth rates and prolonging doubling times. Unloaded NLCs showed no antibacterial activity, and cytotoxicity assays confirmed favorable biocompatibility. Conclusions: Overall, these results show that NLC-based encapsulation can modulate ciprofloxacin release and reshape drug exposure over time, thereby improving antibacterial performance under the tested conditions. This study supports integrated release and growth-kinetic analyses as a more informative framework for evaluating lipid-based antibiotic delivery systems. Full article
(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition)
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17 pages, 3097 KB  
Article
Charge Effects: Influence of Surface Charge on Protein Corona Adsorption Behavior on Liposomal Formulations
by Qian Chen, Yeqi Huang, Chuanbin Wu, Xin Pan, Changjiang Yu, Jiu Wang, Wenhao Wang and Zhengwei Huang
Pharmaceutics 2026, 18(1), 76; https://doi.org/10.3390/pharmaceutics18010076 - 7 Jan 2026
Cited by 3 | Viewed by 1391
Abstract
Background: Liposomes have been successfully used in clinics as an excellent drug delivery system. However, once they enter the body, they adsorb surrounding proteins and form a protein corona, which affects how liposomes behave in vivo. Therefore, controlling the formation of the [...] Read more.
Background: Liposomes have been successfully used in clinics as an excellent drug delivery system. However, once they enter the body, they adsorb surrounding proteins and form a protein corona, which affects how liposomes behave in vivo. Therefore, controlling the formation of the protein corona is crucial for achieving effective treatment outcomes. Among the many variables affecting liposome protein corona formation, the composition of the liposomes themselves and the surrounding ionic environment are two particularly critical factors. Methods: In this context, this study selected bovine serum albumin as a model protein to investigate the influence and mechanism of physiologically relevant inorganic ions (magnesium chloride) and varying proportions of cationic lipid components (1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)) on protein adsorption behavior of liposomes. We evaluated characterization parameters, including particle size and zeta potential, and employed various spectroscopic techniques to elucidate the changes during the interaction between bovine serum albumin and liposomes. Results: The zeta potential results showed that liposomes without DOTAP exhibited a significantly negative potential (−45.20 ± 0.24 mV), while the zeta potential became increasingly positive with higher DOTAP proportions (+19.64 ± 0.39 mV and +51.03 ± 1.74 mV). Correspondingly, the amount of protein adsorption also increased with the rising DOTAP content. Furthermore, fluorescence spectroscopy indicated that the addition of either DOTAP or magnesium ions led to a decrease in both the Ksv and Ka parameters. Conclusions: Specific hypothetical models were advanced subsequently; per the varying proportion of DOTAP, we proposed an insertion or surface adsorption model, and further examined the influence of magnesium chloride on the interactions between the liposomes and proteins. We believe this study will provide a new research paradigm for the design and application of liposomes, laying a foundation for further in vivo investigations. Full article
(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition)
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19 pages, 2932 KB  
Article
PEGylated Terpesome-Loaded 3D-Printed Aripiprazole Ocuserts for the Treatment of Ocular Candidiasis
by Rofida Albash, Mariam Hassan, Ahmed M. Agiba, Wessam H. Abd-Elsalam, Diana Aziz, Youssef R. Hassan, Amira B. Kassem, Asmaa Saleh and Moaz A. Eltabeeb
Pharmaceutics 2025, 17(12), 1616; https://doi.org/10.3390/pharmaceutics17121616 - 16 Dec 2025
Cited by 2 | Viewed by 1115
Abstract
Background/Objectives: This study aimed to repurpose aripiprazole (AR), an antipsychotic clinically approved by the FDA, as a novel antifungal drug and to potentiate its therapeutic efficacy through PEGylated terpesomes (PEG-TERs). Methods: PEG-TERs were prepared by thin-film hydration and optimized using a central composite [...] Read more.
Background/Objectives: This study aimed to repurpose aripiprazole (AR), an antipsychotic clinically approved by the FDA, as a novel antifungal drug and to potentiate its therapeutic efficacy through PEGylated terpesomes (PEG-TERs). Methods: PEG-TERs were prepared by thin-film hydration and optimized using a central composite design. The optimum PEG-TER formulation was characterized for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP), and subsequently integrated into polylactic acid (PLA)-based 3D-printed ocuserts. Results: The optimized formulation exhibited spherical vesicles with high EE%, nanoscale PS, narrow PDI, and favorable ZP, alongside excellent stability and mucoadhesive properties. Ex vivo permeation demonstrated a sustained release profile of AR from PEG-TERs compared with an AR suspension, while confocal microscopy confirmed efficient corneal deposition of fluorescein-labeled PEG-TERs. In vivo, the optimum AR-loaded PEG-TERs ocusert exhibited a substantial therapeutic effect in a rabbit model of Candida albicans keratitis, while histopathological assessment confirmed its ocular safety and biocompatibility. Conclusions: In conclusion, AR-loaded PEG-TERs embedded in PLA-based 3D-printed ocuserts represent a promising, safe, and innovative therapeutic platform for the management of Candida albicans-induced corneal infections, offering both drug repurposing and emerging opportunities in advanced ocular drug delivery. Full article
(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition)
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24 pages, 5557 KB  
Article
The Antidepressant Effect of Targeted Release of Ketamine-Loaded Nanodroplets Stimulated by Low-Intensity Focused Ultrasound
by Bailing Wu, Yu Xu, Yuhang Xie, Youzhuo Li, Yue Huang, Yuran Feng and Mei Zhu
Pharmaceutics 2025, 17(10), 1251; https://doi.org/10.3390/pharmaceutics17101251 - 24 Sep 2025
Cited by 1 | Viewed by 1295
Abstract
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose [...] Read more.
Objectives: Ketamine has demonstrated rapid and sustained antidepressant effects; however, its clinical utility is limited by the risk of addiction and systemic side effects. This study aimed to develop ketamine-loaded nanodroplets (Ket-NDs) with high encapsulation efficiency (EE) and stability for targeted low-dose intravenous (IV) administration in a mice model of depression. Low-intensity focused ultrasound (LIFU) was employed to induce transcranial, region-specific drug release in the lateral habenula (LHb). Methods: Ket-NDs were synthesized using a thin-film hydration method with sonication and emulsification, incorporating perfluoropentane as the core material. Characterization was performed using light microscopy, cryogenic scanning electron microscopy (cryo-SEM), transmission electron microscopy, and dynamic light scattering (DLS). Drug EE and loading efficiency (LE) were quantified by reversed-phase high-performance liquid chromatography. A chronic restraint stress model was established, and Ket-NDs were administered intravenously followed by LIFU targeting the LHb. Antidepressant efficacy and biosafety were systematically evaluated. Results: (1) Ket-NDs exhibited uniform spherical morphology and a narrow size distribution, as confirmed by DLS (particle size: 139.75 ± 9.43 nm; Polydispersity index: 0.225 ± 0.025) and cryo-SEM analysis (number-average diameter: 109.5 ± 10.4 nm). The zeta potential was −15.93 ± 5.906 mV, and the formulation remained stable under 4 °C storage. (2) Ket-NDs demonstrated high EE (78.25 ± 16.13%) and LE (15.55 ± 4.49%). (3) In depressive mice, IV administration of Ket-NDs followed by LIFU targeting the LHb significantly improved behavioral outcomes: increased locomotor activity in the open field test, elevated sucrose preference index, and reduced immobility time in the tail suspension test. (4) Safety assessments revealed no significant organ toxicity or brain tissue damage in ultrasound-exposed regions. Conclusions: In summary, this study developed stable Ket-NDs. When combined with LIFU, they enable precise regional drug delivery to the brain, showcasing a promising treatment strategy for depression with reduced systemic side effects. Full article
(This article belongs to the Special Issue Lipid-Based Nanoparticulate Drug Delivery Systems: Preparation, Biomedical Applications, and Evaluation, 2nd Edition)
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