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Pharmaceutics
Special Issues
Stimuli-Responsive Therapeutic Formulations for Drug Release
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Stimuli-Responsive Therapeutic Formulations for Drug Release

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 (30 June 2023) | Viewed by 6482

Special Issue Editor

Dr. Marina Santiago Franco

E-Mail Website
Guest Editor
Helmholtz Zentrum München German Research Center for Environmental Health (GmbH), Institute for Radiation Medicine (IRM), Ingolstaedter Landstr. 1, 85764 Neuherberg, Germany
Interests: cancer; drug delivery; nanosystems; liposomes; chemotherapy; radiotherapy; microbeams; abscopal effect
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Stimuli-responsive formulations bring the possibility to trigger the release of therapeutic agents at the disease site, providing efficacious drug levels therein. This idea was first introduced back in the 1970s, with thermosensitive liposomes. Since then, stimuli-responsive formulations have been an active field with a vast body of research comprising materials to design these systems as well as different strategies to exploit the outer and inner disease environment as triggering stimuli. Reported extracorporeal physical triggering stimuli include thermal, magnetic, ultrasound, light, chemical, and electric triggers. Formulations can also be sensitive on the tissue level, with endogenous signals such as acidic pH, redox potential (glutathione, GSH), enzymes, hypoxia, or infection, having been explored as trigger stimuli. So far, the main application of these systems has focused on the treatment of tumors and infections.

This Special Issue will highlight current advances and challenges in the broad theme of stimuli-responsive formulations. We encourage the submission of focused review manuscripts as well as original research concerning in vitro, in vivo, and translational studies.

Dr. Marina Santiago Franco
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

  • stimuli-responsive
  • nanosystem
  • nanocarrier
  • nanoparticle
  • liposome
  • drug delivery
  • triggering
  • pH-sensitive
  • thermosensitive
  • cancer
  • tumor
  • infectionc

Published Papers (4 papers)

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Research

27 pages, 6996 KiB  
Article
Bovine Lactoferrin-Loaded Plasmonic Magnetoliposomes for Antifungal Therapeutic Applications
by Mélanie Pereira, Ana Rita O. Rodrigues, Leslie Amaral, Manuela Côrte-Real, Cátia Santos-Pereira and Elisabete M. S. Castanheira
Pharmaceutics 2023, 15(8), 2162; https://doi.org/10.3390/pharmaceutics15082162 - 19 Aug 2023
Viewed by 1035
Abstract
Bovine lactoferrin (bLf) is a milk-derived protein that exhibits potent broad-spectrum antifungal activity against multiple fungi. bLf is susceptible to degradation, while some of its properties depend on the tertiary structure. So, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added [...] Read more.
Bovine lactoferrin (bLf) is a milk-derived protein that exhibits potent broad-spectrum antifungal activity against multiple fungi. bLf is susceptible to degradation, while some of its properties depend on the tertiary structure. So, the encapsulation of bLf in stimuli-responsive therapeutic formulations provides an added value to enhance its biological activities. Plasmonic magnetoliposomes (PMLs) arise as promising nanocarriers for dual hyperthermia (magneto-photothermia) and local chemotherapy, since the combination of magnetic and gold nanoparticles (NPs) in a single nanosystem (multifunctional liposomes) enables the targeting and controlled release of loaded drugs. In this work, plasmonic magnetoliposomes (PMLs) containing manganese ferrite nanoparticles (28 nm size) and gold nanoparticles (5–7.5 nm size), functionalized with 11-mercaptoundecanoic acid or octadecanethiol, were prepared and loaded with bLf. The NPs’ optical, magnetic and structural properties were measured via UV/vis/NIR absorption spectroscopy, SQUID and TEM, respectively. The Specific Absorption Rate (SAR) was calculated to assess the capabilities for magnetic and photothermal hyperthermia. Finally, the antifungal potential of bLf-loaded PMLs and their mechanism of internalization were assessed in Saccharomyces cerevisiae by counting the colony forming units and using fluorescence microscopy. The results demonstrate that PMLs are mainly internalized through an energy- and temperature-dependent endocytic process, though the contribution of a diffusion component cannot be discarded. Most notably, only bLf-loaded plasmonic magnetoliposomes display cytotoxicity with an efficiency similar to free bLf, attesting their promising potential for bLf delivery in the context of antifungal therapeutic interventions. Full article
(This article belongs to the Special Issue Stimuli-Responsive Therapeutic Formulations for Drug Release)
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23 pages, 11781 KiB  
Article
Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment
by Yu-Jen Lu, Hao-Lung Hsu, Yu-Hsiang Lan and Jyh-Ping Chen
Pharmaceutics 2023, 15(4), 1169; https://doi.org/10.3390/pharmaceutics15041169 - 06 Apr 2023
Cited by 7 | Viewed by 1575
Abstract
Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in [...] Read more.
Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment. Full article
(This article belongs to the Special Issue Stimuli-Responsive Therapeutic Formulations for Drug Release)
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21 pages, 6015 KiB  
Article
Advanced Skin Antisepsis: Application of UVA-Cleavable Hydroxyethyl Starch Nanocapsules for Improved Eradication of Hair Follicle-Associated Microorganisms
by Loris Busch, Anna Maria Hanuschik, Yuri Avlasevich, Katrin Darm, Elisa F. Hochheiser, Christian Kohler, Evgeny A. Idelevich, Karsten Becker, Peter Rotsch, Katharina Landfester, Maxim E. Darvin, Martina C. Meinke, Cornelia M. Keck, Axel Kramer and Paula Zwicker
Pharmaceutics 2023, 15(2), 609; https://doi.org/10.3390/pharmaceutics15020609 - 11 Feb 2023
Cited by 1 | Viewed by 1629
Abstract
Hair follicles constitute important drug delivery targets for skin antisepsis since they contain ≈25% of the skin microbiome. Nanoparticles are known to penetrate deeply into hair follicles. By massaging the skin, the follicular penetration process is enhanced based on a ratchet effect. Subsequently, [...] Read more.
Hair follicles constitute important drug delivery targets for skin antisepsis since they contain ≈25% of the skin microbiome. Nanoparticles are known to penetrate deeply into hair follicles. By massaging the skin, the follicular penetration process is enhanced based on a ratchet effect. Subsequently, an intrafollicular drug release can be initiated by various trigger mechanisms. Here, we present novel ultraviolet A (UVA)-responsive nanocapsules (NCs) with a size between 400 and 600 nm containing hydroxyethyl starch (HES) functionalized by an o-nitrobenzyl linker. A phase transfer into phosphate-buffered saline (PBS) and ethanol was carried out, during which an aggregation of the particles was observed by means of dynamic light scattering (DLS). The highest stabilization for the target medium ethanol as well as UVA-dependent release of ethanol from the HES-NCs was achieved by adding 0.1% betaine monohydrate. Furthermore, sufficient cytocompatibility of the HES-NCs was demonstrated. On ex vivo porcine ear skin, a strong UVA-induced release of the model drug sulforhodamine 101 (SR101) could be demonstrated after application of the NCs in cyclohexane using laser scanning microscopy. In a final experiment, a microbial reduction comparable to that of an ethanol control was demonstrated on ex vivo porcine ear skin using a novel UVA-LED lamp for triggering the release of ethanol from HES-NCs. Our study provides first indications that an advanced skin antisepsis based on the eradication of intrafollicular microorganisms could be achieved by the topical application of UVA-responsive NCs. Full article
(This article belongs to the Special Issue Stimuli-Responsive Therapeutic Formulations for Drug Release)
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20 pages, 6547 KiB  
Article
Easy Synthesis and Characterization of Novel Carbon Dots Using the One-Pot Green Method for Cancer Therapy
by Lijie Wang, Donghao Gu, Yupei Su, Dongxu Ji, Yue Yang, Kai Chen, Hao Pan and Weisan Pan
Pharmaceutics 2022, 14(11), 2423; https://doi.org/10.3390/pharmaceutics14112423 - 09 Nov 2022
Cited by 6 | Viewed by 1538
Abstract
In this study, hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) were used for the synthesis of novel targeted nanocarrier carbon dots (CDC-H) with photo-luminescence using a one-step hydrothermal method. Doxorubicin (DOX), a common chemotherapeutic agent, was loaded with the CDC-H [...] Read more.
In this study, hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) were used for the synthesis of novel targeted nanocarrier carbon dots (CDC-H) with photo-luminescence using a one-step hydrothermal method. Doxorubicin (DOX), a common chemotherapeutic agent, was loaded with the CDC-H through electrostatic interactions to form DOX–CDC-H complexes as a targeted antitumor drug delivery system. The synthesized CDC-H show a particle size of approximately 6 nm and a high fluorescence quantum yield of 11.64%. The physical and chemical character properties of CDC-H and DOX–CDC-H complexes were investigated using various techniques. The results show that CDC-H have stable luminescent properties and exhibit excellent water solubility. The in vitro release study showed that DOX–CDC-H exhibited pH-dependent release for 24 h. Confocal laser scanning microscopy was applied to investigate the potential of CDC-H for cell imaging and the cellular uptake of DOX–CDC-H in different cells (NIH-3T3 and 4T1 cells), and the results confirmed the target cell imaging and cellular uptake of DOX–CDC-H by specifically binding the CD44 receptors on the surface of tumor cells. The r MTT results suggest that the DOX–CDC-H complex may induce apoptosis in 4T1 cells, reducing the cytotoxicity of free DOX-induced apoptosis. In vivo antitumor experiments of DOX–CDC-H exhibited enhanced tumor cancer therapy. CDC-H have potential applications in bioimaging and antitumor drug delivery. Full article
(This article belongs to the Special Issue Stimuli-Responsive Therapeutic Formulations for Drug Release)
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