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Pharmaceutics
Special Issues
Hybrid Multifunctional Drug Delivery Systems
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Hybrid Multifunctional Drug Delivery Systems

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 (31 August 2020) | Viewed by 33778

Special Issue Editors

Assist. Prof. Alexandra Teleki

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Guest Editor
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Interests: enabling formulations; nanoparticles; microencapsulation technologies; nanomedicine, additive manufacturing; oral drug delivery; particle engineering; lipid-based formulations
Prof. Dr. Jessica Rosenholm

E-Mail Website
Guest Editor
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
Interests: nanomedicine; drug delivery; biomaterials engineering; bioimaging probes; biomedical nanotechnology; pharmaceutical technology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Line Hagner Nielsen

E-Mail Website
Guest Editor
DTU Health Tech, Department of Health Technology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
Interests: oral drug delivery; microdevices; targeted delivery; drug formulations; vaccine delivery; peptide delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Remarkable developments have been made in the field of particulate-based drug delivery systems to overcome hurdles associated with conventional drug formulations for diagnostic and therapeutic applications. The vast array of today’s nano- and microparticle platforms include polymeric nanoparticles, lipid carrier systems (i.e., liposomes, solid lipid nanoparticles, and nanostructured lipid carriers) as well as different types of inorganic particles (i.e., quantum dots, mesoporous materials, and metal oxides). Hybrid drug carriers combine structural components from two or more (typically organic and inorganic) materials and are the next frontier in the development of novel, multifunctional drug delivery systems, as they benefit from the synergistic properties of the individual components. Typical examples include functionalization of inorganic particles with organic constructs combining structural robustness with functional responsiveness. This course of action is usually taken in order to enhance drug encapsulation efficiency and to control drug release, or for the design of theranostic nanomaterials for simultaneous imaging and therapy.

The aim of this Special Issue is to highlight recent advances in all aspects relevant to hybrid multifunctional drug delivery systems, with a focus on particle-based systems, ranging from synthesis methods and process understanding, their detailed physicochemical characterization and performance in vitro and in vivo, especially for controlled and/or targeted drug delivery applications. 

Assist. Prof. Alexandra Teleki
Prof. Jessica Rosenholm
Assoc. Prof. Line Hagner Nielsen
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

  • nanotechnology
  • drug delivery
  • hybrid materials
  • nanocomposite
  • nanoparticles
  • nanocarriers
  • multifunctional
  • multimodal
  • theranostics
  • targeted delivery
  • nanotherapeutics

Published Papers (7 papers)

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Research

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25 pages, 5962 KiB  
Article
Delivery of Protein Kinase A by CRISPRMAX and Its Effects on Breast Cancer Stem-Like Properties
by Jun-Nian Zhou, Tzu-Chen Rautio, Chang Liu, Xiao-Yu Xu, Dong-Qing Wang, Yong Guo, John Eriksson and Hongbo Zhang
Pharmaceutics 2021, 13(1), 11; https://doi.org/10.3390/pharmaceutics13010011 - 23 Dec 2020
Cited by 4 | Viewed by 6114
Abstract
Protein kinase A (PKA) activation has recently been reported to inhibit epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) ability, which is considered to be responsible for chemoresistance and tumor recurrence in patients. While current studies mainly focus on gene manipulation of the [...] Read more.
Protein kinase A (PKA) activation has recently been reported to inhibit epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) ability, which is considered to be responsible for chemoresistance and tumor recurrence in patients. While current studies mainly focus on gene manipulation of the EMT process, the direct delivery of PKA enzymes to cancer cells has never been investigated. Here, we utilize the commercial Lipofectamine CRISPRMAX reagent to directly deliver PKAs to breast cancer cells and evaluate its effects on EMT regulation. We optimized the delivery parameters with fluorescent-labeled bovine serum albumin, and successfully delivered fluorescent PKAs through CRISPRMAX into breast cancer cells. Then, we evaluated the biological effects by immunofluorescence, flow cytometry, mammosphere assay, and chemoresistance assay. Our data showed the expression of EMT-related markers, α-smooth muscle actin and N-cadherin, was downregulated after CRISPRMAX-PKA treatment. Although the CD44+/CD24− population did not change considerably, the size of mammospheres significantly decreased. In paclitaxel and doxorubicin chemoresistance assays, we noticed PKA delivery significantly inhibited paclitaxel resistance rather than doxorubicin resistance. Taken together, these results suggest our direct enzyme delivery can be a potential strategy for inhibiting EMT/CSC-associated traits, providing a safer approach and having more clinical translational efficacy than gene manipulation. This strategy will also facilitate the direct testing of other target enzymes/proteins on their biological functions. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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23 pages, 3297 KiB  
Article
Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes
by Joachim Delasoie, Philippe Schiel, Sandra Vojnovic, Jasmina Nikodinovic-Runic and Fabio Zobi
Pharmaceutics 2020, 12(5), 480; https://doi.org/10.3390/pharmaceutics12050480 - 25 May 2020
Cited by 26 | Viewed by 5239
Abstract
Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and [...] Read more.
Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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15 pages, 2186 KiB  
Article
In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier
by Caroline Alvebratt, Tahnee J. Dening, Michelle Åhlén, Ocean Cheung, Maria Strømme, Adolf Gogoll, Clive A. Prestidge and Christel A.S. Bergström
Pharmaceutics 2020, 12(5), 426; https://doi.org/10.3390/pharmaceutics12050426 - 06 May 2020
Cited by 8 | Viewed by 3459
Abstract
Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the [...] Read more.
Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with 1H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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14 pages, 3415 KiB  
Article
Light-Activatable Transfection System Using Hybrid Vectors Composed of Thermosensitive Dendron Lipids and Gold Nanorods
by Takuya Hashimoto, Tomoya Hirata, Eiji Yuba, Atsushi Harada and Kenji Kono
Pharmaceutics 2020, 12(3), 239; https://doi.org/10.3390/pharmaceutics12030239 - 07 Mar 2020
Cited by 1 | Viewed by 3451
Abstract
Background: Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this [...] Read more.
Background: Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this study, both light-responsive and temperature-responsive synthetic gene vectors were designed for spatiotemporal control of a transfection system. Methods: 11-Mercaptoundecanoic acid-coated gold nanorods were mixed with polyamidoamine dendron-bearing lipids of two types having amino-terminus or ethoxydiethylene glycol-terminus to obtain hybrid vectors. Hybrid vectors were mixed further with pDNA. Then we investigated their physicochemical properties and transfection efficacy with or without near infrared laser irradiation. Results: Hybrid vectors formed complexes with pDNA and exhibited enhanced photothermal property under near infrared laser irradiation compared with parent gold nanorods. Transfection efficacy of complexes was promoted considerably by brief laser irradiation soon after complex application to the cells. Analysis of intracellular distribution revealed that laser irradiation promoted the adsorption of complexes to the cells and cytosolic release of pDNA, which is derived from the change in surface hydrophobicity of complexes through dehydration of temperature-responsive groups. Conclusions: Hybrid vector is promising as a light-activatable transfection system. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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Review

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17 pages, 2941 KiB  
Review
Uniting Drug and Delivery: Metal Oxide Hybrid Nanotherapeutics for Skin Wound Care
by Martin T. Matter, Sebastian Probst, Severin Läuchli and Inge K. Herrmann
Pharmaceutics 2020, 12(8), 780; https://doi.org/10.3390/pharmaceutics12080780 - 17 Aug 2020
Cited by 30 | Viewed by 6433
Abstract
Wound care and soft tissue repair have been a major human concern for millennia. Despite considerable advancements in standards of living and medical abilities, difficult-to-heal wounds remain a major burden for patients, clinicians and the healthcare system alike. Due to an aging population, [...] Read more.
Wound care and soft tissue repair have been a major human concern for millennia. Despite considerable advancements in standards of living and medical abilities, difficult-to-heal wounds remain a major burden for patients, clinicians and the healthcare system alike. Due to an aging population, the rise in chronic diseases such as vascular disease and diabetes, and the increased incidence of antibiotic resistance, the problem is set to worsen. The global wound care market is constantly evolving and expanding, and has yielded a plethora of potential solutions to treat poorly healing wounds. In ancient times, before such a market existed, metals and their ions were frequently used in wound care. In combination with plant extracts, they were used to accelerate the healing of burns, cuts and combat wounds. With the rise of organic chemistry and small molecule drugs and ointments, researchers lost their interest in inorganic materials. Only recently, the advent of nano-engineering has given us a toolbox to develop inorganic materials on a length-scale that is relevant to wound healing processes. The robustness of synthesis, as well as the stability and versatility of inorganic nanotherapeutics gives them potential advantages over small molecule drugs. Both bottom-up and top-down approaches have yielded functional inorganic nanomaterials, some of which unite the wound healing properties of two or more materials. Furthermore, these nanomaterials do not only serve as the active agent, but also as the delivery vehicle, and sometimes as a scaffold. This review article provides an overview of inorganic hybrid nanotherapeutics with promising properties for the wound care field. These therapeutics include combinations of different metals, metal oxides and metal ions. Their production, mechanism of action and applicability will be discussed in comparison to conventional wound healing products. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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25 pages, 4616 KiB  
Review
Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers
by Sybil Obuobi and Nataša Škalko-Basnet
Pharmaceutics 2020, 12(7), 643; https://doi.org/10.3390/pharmaceutics12070643 - 08 Jul 2020
Cited by 8 | Viewed by 3577
Abstract
Conventional antibiotic therapy is often challenged by poor drug penetration/accumulation at infection sites and poses a significant burden to public health. Effective strategies to enhance the therapeutic efficacy of our existing arsenal include the use of nanoparticulate delivery platforms to improve drug targeting [...] Read more.
Conventional antibiotic therapy is often challenged by poor drug penetration/accumulation at infection sites and poses a significant burden to public health. Effective strategies to enhance the therapeutic efficacy of our existing arsenal include the use of nanoparticulate delivery platforms to improve drug targeting and minimize adverse effects. However, these nanocarriers are often challenged by poor loading efficiency, rapid release and inefficient targeting. Nucleic acid hybrid nanocarriers are nucleic acid nanosystems complexed or functionalized with organic or inorganic materials. Despite their immense potential in antimicrobial therapy, they are seldom utilized against pathogenic bacteria. With the emergence of antimicrobial resistance and the associated complex interplay of factors involved in antibiotic resistance, nucleic acid hybrids represent a unique opportunity to deliver antimicrobials against resistant pathogens and to target specific genes that control virulence or resistance. This review provides an unbiased overview on fabricating strategies for nucleic acid hybrids and addresses the challenges of pristine oligonucleotide nanocarriers. We report recent applications to enhance pathogen targeting, binding and control drug release. As multifunctional next-generational antimicrobials, the challenges and prospect of these nanocarriers are included. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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27 pages, 7188 KiB  
Review
Recent Advances and Impact of Chemotherapeutic and Antiangiogenic Nanoformulations for Combination Cancer Therapy
by Amit Kumar Rajora, Divyashree Ravishankar, Hongbo Zhang and Jessica M. Rosenholm
Pharmaceutics 2020, 12(6), 592; https://doi.org/10.3390/pharmaceutics12060592 - 25 Jun 2020
Cited by 25 | Viewed by 4143
Abstract
Traditional chemotherapy, along with antiangiogenesis drugs (combination cancer therapy), has shown reduced tumor recurrence and improved antitumor effects, as tumor growth and metastasis are often dependent on tumor vascularization. However, the effect of combination chemotherapy, including synergism and additive and even antagonism effects, [...] Read more.
Traditional chemotherapy, along with antiangiogenesis drugs (combination cancer therapy), has shown reduced tumor recurrence and improved antitumor effects, as tumor growth and metastasis are often dependent on tumor vascularization. However, the effect of combination chemotherapy, including synergism and additive and even antagonism effects, depends on drug combinations in an optimized ratio. Hence, nanoformulations are ideal, demonstrating a great potential for the combination therapy of chemo-antiangiogenesis for cancer. The rationale for designing various nanocarriers for combination therapy is derived from organic (polymer, lipid), inorganic, or hybrid materials. In particular, hybrid nanocarriers that consist of more than one material construct provide flexibility for different modes of entrapment within the same carrier—e.g., physical adsorption, encapsulation, and chemical conjugation strategies. These multifunctional nanocarriers can thus be used to co-deliver chemo- and antiangiogenesis drugs with tunable drug release at target sites. Hence, this review attempts to survey the most recent advances in nanoformulations and their impact on cancer treatment in a combined regimen—i.e., conventional cytotoxic and antiangiogenesis agents. The mechanisms and site-specific co-delivery strategies are also discussed herein, along with future prospects. Full article
(This article belongs to the Special Issue Hybrid Multifunctional Drug Delivery Systems)
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