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Pharmaceutics
Special Issues
Recent Trends in Nano-Based Drug Delivery Systems
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Recent Trends in Nano-Based Drug Delivery Systems

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

Deadline for manuscript submissions: closed (10 September 2023) | Viewed by 10730

Special Issue Editors

Prof. Dr. Rita Muzzalupo

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: colloid systems; multifunctional nanoparticles; transdermal and topical delivery; polymeric nanoparticles; controlled release
Special Issues, Collections and Topics in MDPI journals
Dr. Elisabetta Mazzotta

E-Mail Website
Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Ed. Polifunzionale, 87036 Arcavacata di Rende, Italy
Interests: multifunctional nanoparticles; active targeting; stimuli responsivity; transdermal and topical delivery; niosomes; chitosan nanoparticles

Special Issue Information

Dear Colleagues,

Nano-based drug delivery systems have emerged as innovative and smart scaffolds that are able to improve the clinical outcomes of traditional drugs. The majority of the benefits of these devices are directly related to their small size and high surface area and reactivity, which enable them to be tailor-made for the desired therapeutic purpose.  They can be designed differently to simultaneously perform multiple functions, such as active targeting, stimuli responsivity and imaging. These fine-tuned devices may enhance the specific delivery of a drug at the target site, improving the therapeutic efficacy and reducing systemic toxicity. In this context, the final aim of this Special Issue is to provide an overview of the recent studies reporting innovative design strategies and results regarding the in vitro, in vivo and  clinical  efficacy of these systems in topical and transdermal therapy, cancer target therapy, gene therapy, immunotherapy and theranostics.

We look forward to receiving your contributions.

Prof. Dr. Rita Muzzalupo
Dr. Elisabetta Mazzotta
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 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

  • smart drug delivery systems
  • multifunctional nanoparticles
  • topical and transdermal drug delivery systems
  • active targeting
  • stimuli responsivity
  • target cancer therapy
  • immunotherapy
  • gene therapy

Published Papers (7 papers)

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Research

18 pages, 6808 KiB  
Article
Liposomes Coated with Novel Synthetic Bifunctional Chitosan Derivatives as Potential Carriers of Anticancer Drugs
by Elisabetta Mazzotta, Antonia Marazioti, Spyridon Mourtas, Rita Muzzalupo and Sophia G. Antimisiaris
Pharmaceutics 2024, 16(3), 319; https://doi.org/10.3390/pharmaceutics16030319 - 24 Feb 2024
Viewed by 722
Abstract
In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes [...] Read more.
In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes were characterized for size, surface charge and drug encapsulation efficiency before and after coating. The formation of a coating layer on liposomal surface was confirmed by the slight increase in particle size and by zeta-potential changes. FTC-coated liposomes showed a redox-dependent drug release profile: good stability at physiological conditions and rapid release of liposome-entrapped calcein in presence of glutathione. Moreover, the uptake and cytotoxic activity of doxorubicin-loaded FTC-coated liposomes was evaluated on murine B16-F10 and human SKMEL2 melanoma cancer cells. Results demonstrated enhanced uptake and antitumor efficacy of FTC-coated liposomes compared to control chitosan-coated liposomes in both cancer lines, which is attributed to higher cellular uptake via folate receptor-mediated endocytosis and to triggered drug release by the reductive microenvironment of tumor cells. The proposed novel liposomes show great potential as nanocarriers for targeted therapy of cancer. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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11 pages, 1930 KiB  
Article
Cis-2-Decenoic Acid and Bupivacaine Delivered from Electrospun Chitosan Membranes Increase Cytokine Production in Dermal and Inflammatory Cell Lines
by Zoe Harrison, Emily C. Montgomery, Joshua R. Bush, Nidhi Gupta, Joel D. Bumgardner, Tomoko Fujiwara, Daniel L. Baker and Jessica Amber Jennings
Pharmaceutics 2023, 15(10), 2476; https://doi.org/10.3390/pharmaceutics15102476 - 17 Oct 2023
Viewed by 990
Abstract
Wound dressings serve to protect tissue from contamination, alleviate pain, and facilitate wound healing. The biopolymer chitosan is an exemplary choice in wound dressing material as it is biocompatible and has intrinsic antibacterial properties. Infection can be further prevented by loading dressings with [...] Read more.
Wound dressings serve to protect tissue from contamination, alleviate pain, and facilitate wound healing. The biopolymer chitosan is an exemplary choice in wound dressing material as it is biocompatible and has intrinsic antibacterial properties. Infection can be further prevented by loading dressings with cis-2-decenoic acid (C2DA), a non-antibiotic antimicrobial agent, as well as bupivacaine (BUP), a local anesthetic that also has antibacterial capabilities. This study utilized a series of assays to elucidate the responses of dermal cells to decanoic anhydride-modified electrospun chitosan membranes (DA-ESCMs) loaded with C2DA and/or BUP. Cytocompatibility studies determined the toxic loading ranges for C2DA, BUP, and combinations, revealing that higher concentrations (0.3 mg of C2DA and 1.0 mg of BUP) significantly decreased the viability of fibroblasts and keratinocytes. These high concentrations also inhibited collagen production by fibroblasts, with lower loading concentrations promoting collagen deposition. These findings provide insight into preliminary cellular responses to DA-ESCMs and can guide future research on their clinical application as wound dressings. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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29 pages, 5892 KiB  
Article
Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation
by Zakaria Hafidi, Lourdes Pérez, Mohammed El Achouri and Ramon Pons
Pharmaceutics 2023, 15(7), 1856; https://doi.org/10.3390/pharmaceutics15071856 - 30 Jun 2023
Cited by 1 | Viewed by 1390
Abstract
Cationic surfactants based on phenylalanine (CnPC3NH3Cl) and tryptophan (CnTC3NH3Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial [...] Read more.
Cationic surfactants based on phenylalanine (CnPC3NH3Cl) and tryptophan (CnTC3NH3Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of CnPC3NH3Cl and CnTC3NH3Cl occurred in the ranges of 0.42–16.2 mM and 0.29–4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pKa was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C12TC3NH3Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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18 pages, 2331 KiB  
Article
Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery
by Maria De Luca, Carlo Ignazio Giovanni Tuberoso, Ramon Pons, María Teresa García, María del Carmen Morán, Giulio Ferino, Antonio Vassallo, Giuseppe Martelli and Carla Caddeo
Pharmaceutics 2023, 15(4), 1063; https://doi.org/10.3390/pharmaceutics15041063 - 25 Mar 2023
Cited by 4 | Viewed by 1311
Abstract
The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. [...] Read more.
The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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19 pages, 8481 KiB  
Article
Facile Synthesis of Magnetic Nigella Sativa Seeds: Advances on Nano-Formulation Approaches for Delivering Antioxidants and Their Antifungal Activity against Candida albicans
by Maqsood Ahmad Malik, Laila AlHarbi, Arshid Nabi, Khalid Ahmed Alzahrani, Katabathini Narasimharao and Majid Rasool Kamli
Pharmaceutics 2023, 15(2), 642; https://doi.org/10.3390/pharmaceutics15020642 - 14 Feb 2023
Cited by 4 | Viewed by 1654
Abstract
This article reports on incorporating magnetic nanoparticles into natural carbon frameworks derived from Nigella Sativa seeds and their synthesis via co-precipitation reactions for application in biomedicine. The magnetic Nigella Sativa Seeds (Magnetic NSS), a metal oxide-based bio-nanomaterial, has shown excellent water diaper presence [...] Read more.
This article reports on incorporating magnetic nanoparticles into natural carbon frameworks derived from Nigella Sativa seeds and their synthesis via co-precipitation reactions for application in biomedicine. The magnetic Nigella Sativa Seeds (Magnetic NSS), a metal oxide-based bio-nanomaterial, has shown excellent water diaper presence due to the presence of a wide range of oxygenous hydroxyl and carboxyl groups. The physicochemical properties of the composites were characterized extensively using Fourier transform infrared spectroscopy (FTIR), powder-X-ray diffraction (XRD), scanning electron microscopy (SEM), elemental analysis, transmission electron microscopy (TEM), and vibrating-sample magnetometer. Furthermore, synthesized magnetic NSS showed antioxidant and antifungal activity. The antifungal susceptibility was further tested against Candida albicans with a MIC value of 3.125 µg/mL. Analysis of antioxidant defense enzymes was determined quantitatively; the results suggested that antioxidant enzyme activity increase with increased magnetic NSS concentration. Furthermore, biofilm inhibition assay from scanning electron microscopy results revealed that magnetic NSS at the concentration of 3.5 μg/mL has anti-biofilm properties and can disrupt membrane integrity. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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28 pages, 5306 KiB  
Article
Cationic Surfactants Based on Arginine-Phenylalanine and Arginine-Tryptophan: Synthesis, Aggregation Behavior, Antimicrobial Activity, and Biodegradation
by Lourdes Pérez, María Teresa García, Aurora Pinazo, Edgar Pérez-Matas, Zakaria Hafidi and Elena Bautista
Pharmaceutics 2022, 14(12), 2602; https://doi.org/10.3390/pharmaceutics14122602 - 25 Nov 2022
Cited by 8 | Viewed by 2425
Abstract
Cationic surfactants have great potential as drug vehicles and for use in gene therapy (cationic vesicles made from cationic surfactants can encapsulate RNA or DNA for cellular transfer). They can also be used as antimicrobial and antifungal agents to treat human infections. In [...] Read more.
Cationic surfactants have great potential as drug vehicles and for use in gene therapy (cationic vesicles made from cationic surfactants can encapsulate RNA or DNA for cellular transfer). They can also be used as antimicrobial and antifungal agents to treat human infections. In an era of increasing antimicrobial resistance, the development of new biocompatible surfactants suitable for application as antimicrobial agents is of high interest. In this work, a library of amino acid-based surfactants was synthesized, characterized and tested for antimicrobial activity. The head group architecture (number and type of amino acids, density of cationic charge, ionic character) and the hydrophobic moiety (alkyl chain length and position of the hydrophobic group) were systematically modified, and the effect on the surfactant biological and aggregation behavior was studied. Thus, the pKa values, micellization process, antimicrobial efficiency and biodegradability were evaluated. The critical micelle concentration values of the surfactants depended on their hydrophobic character, but changes in the polar head as well as the position and length of the alkyl chain also significantly affected activity against some of the tested microorganisms. Moreover, biodegradability was closely related to the hydrophobic character of the surfactant and attachment of the alkyl chain to the polar head. The structure–activity relationships established here may open perspectives for the design of effective biodegradable antimicrobial materials that can overcome emerging resistance. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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12 pages, 2844 KiB  
Article
Enhancement of the In Vitro Antitumor Effects of Berberine Chloride When Encapsulated within Small Extracellular Vesicles
by Abir Salek, Mouna Selmi, Mahassen Barboura, M. Carmen Martinez, Leila Chekir-Ghedira and Ramaroson Andriantsitohaina
Pharmaceutics 2022, 14(9), 1913; https://doi.org/10.3390/pharmaceutics14091913 - 09 Sep 2022
Cited by 3 | Viewed by 1483
Abstract
Berberine hydrochloride (BRB) is an isoquinoline alkaloid with promising anticancer efficacies. However, application of BRB had been hampered by its poor aqueous solubility, low gastrointestinal absorption, and rapid metabolism. The present study takes advantage of small extracellular vesicles (sEVs) to increase both stability [...] Read more.
Berberine hydrochloride (BRB) is an isoquinoline alkaloid with promising anticancer efficacies. However, application of BRB had been hampered by its poor aqueous solubility, low gastrointestinal absorption, and rapid metabolism. The present study takes advantage of small extracellular vesicles (sEVs) to increase both stability and efficacy of BRB. sEVs from immature dendritic cells were produced and loaded with BRB. Proliferation, migration and Matrigel assay were performed, cycle arrest and nitric oxide (NO) production were evaluated in human breast cancer cell line (MDA-MB-231) and human umbilical vein endothelial cells (HUVECs). sEVs loaded with BRB formed a stable and homogenous population with a drug entrapment efficiency near to 42%. BRB loaded into sEVs was more potent than free BRB for MDA-MB-231 and endothelial proliferation, migration, and capillary-like formation in HUVECs. The mechanisms involved a blockade of cell cycle in G0/G1 phase, increased S phase and decreased of G2/M in MDA-MB-231 and HUVECs, and inhibition of NO production in HUVECs. Altogether, sEV-loaded BRB displayed higher effects than free BRB on different steps leading to its antitumor activity and anti-angiogenic properties in vitro. Thus, sEV formulation may be considered as an innovative approach and promising delivery of BRB to prevent tumorigenesis and angiogenesis. Full article
(This article belongs to the Special Issue Recent Trends in Nano-Based Drug Delivery Systems)
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