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Pharmaceutics
Special Issues
Recent Advances in Cyclodextrins-Based Drug Delivery Systems
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Recent Advances in Cyclodextrins-Based 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 December 2023) | Viewed by 5081

Special Issue Editors

Prof. Dr. Marisa C. F. Barros

E-Mail Website
Guest Editor
Department of Chemistry, University of Coimbra, 3004 - 535 Coimbra, Portugal
Interests: transport properties; cyclodextrins; drug delivery; thermodynamic properties; thermodiffusion; supercritical fluids; supercritical CO2
Prof. Dr. Cecília I. A. V. Santos

E-Mail Website
Guest Editor
Department of Chemistry, University of Coimbra, 3004 - 535 Coimbra, Portugal
Interests: transport properties; cyclodextrins; drug delivery; thermodynamic properties; thermodiffusion; supercritical fluids; supercritical CO2

Special Issue Information

Dear Colleagues,

As guest editors, we are pleased to invite you to contribute to a new Special Issue entitled “Recent Advances in Cyclodextrins-Based Drug Delivery Systems”.

Cyclodextrin drug delivery systems remain a frontier research area due to the constant hunt for new drug delivery approaches and new models of action. This is a direct result of cyclodextrins’ multi-functional characteristics and bioadaptability, that allow them to encapsulate a drug molecule, improving the unfavourable physicochemical and the biological properties of the hosted molecule and release them in a controlled way, in accordance with the therapeutic purpose and the pharmacological properties of the drug.

The aim of this Special Issue is to disclose the state of the art and recent findings in the research field of cyclodextrin drug delivery systems.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: trends in novel cyclodextrin drug release systems, studies in drug–cyclodextrin molecular interactions, transport properties of drugs and cyclodextrin carriers, the role of cyclodextrins in developing new drug delivery systems, etc. Additionally, researchers are encouraged to submit articles or reviews that include existing and new methodologies suitable for studying drug–cyclodextrin interactions or their transport and thermodynamic properties as the molecular nature of these interactions is critical for understanding their encapsulation mechanism and for rational drug design. Furthermore, research articles and review papers on cyclodextrin design, development, and characterization for application in drug design are also suitable for this Special Issue.

We look forward to receiving your contributions.

Prof. Dr. Marisa C. F. Barros
Prof. Dr. Cecília I. A. V. Santos
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

  • cyclodextrins
  • drugs
  • drug delivery systems
  • transport properties
  • molecular interactions

Published Papers (3 papers)

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Research

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14 pages, 3146 KiB  
Article
Preparation and Characterisation of Zinc Diethyldithiocarbamate–Cyclodextrin Inclusion Complexes for Potential Lung Cancer Treatment
by Ayşe Kaya, Basel Arafat, Havovi Chichger, Ibrahim Tolaymat, Barbara Pierscionek, Mouhamad Khoder and Mohammad Najlah
Pharmaceutics 2024, 16(1), 65; https://doi.org/10.3390/pharmaceutics16010065 - 31 Dec 2023
Viewed by 2096
Abstract
Zinc diethyldithiocarbamate (Zn (DDC)2), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)2 is [...] Read more.
Zinc diethyldithiocarbamate (Zn (DDC)2), a disulfiram metabolite (anti-alcoholism drug), has shown a strong anti-cancer activity in vitro. However, its application was limited by its low aqueous solubility and rapid metabolism. In this study, the solubility enhancement of Zn (DDC)2 is investigated by forming inclusion complexes with cyclodextrins. The inclusion complexes were prepared using two different types of beta-cyclodextrins, SBE-CD and HP-CD. Phase solubility diagrams for the resulting solutions were assessed; subsequently, the solutions were freeze-dried for further characterisation studies using DSC, TGA, XRD, and FTIR. The cytotoxic activity of the produced inclusion complexes was evaluated on human lung carcinoma cells using the MTT assay. The solubility of Zn (DDC)2 increased significantly upon adding beta-cyclodextrins, reaching approximately 4 mg/mL for 20% w/w CD solutions. The phase solubility diagram of Zn (DDC)2 was of the Ap-type according to the Higuchi and Connors model. Characterisation studies confirmed the inclusion of the amorphous drug in the CD-Zn (DDC)2 complexes. The cytotoxicity of Zn (DDC)2 was enhanced 10-fold by the inclusion complexes compared to the free drug. Overall, the resulting CD-Zn (DDC)2 inclusion complexes have a potential for treatment against lung cancer. Full article
(This article belongs to the Special Issue Recent Advances in Cyclodextrins-Based Drug Delivery Systems)
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23 pages, 7521 KiB  
Article
Continuous Manufacturing of Solvent-Free Cyclodextrin Inclusion Complexes for Enhanced Drug Solubility via Hot-Melt Extrusion: A Quality by Design Approach
by Siva Ram Munnangi, Ahmed Adel Ali Youssef, Nagarjuna Narala, Preethi Lakkala, Sateesh Kumar Vemula, Rohit Alluri, Feng Zhang and Micheal A. Repka
Pharmaceutics 2023, 15(9), 2203; https://doi.org/10.3390/pharmaceutics15092203 - 25 Aug 2023
Cited by 2 | Viewed by 1261
Abstract
Conventional cyclodextrin complexation enhances the solubility of poorly soluble drugs but is solvent-intensive and environmentally unfavorable. This study evaluated solvent-free hot-melt extrusion (HME) for forming cyclodextrin inclusion complexes to improve the solubility and dissolution of ibuprofen (IBU). Molecular docking confirmed IBU’s hosting in [...] Read more.
Conventional cyclodextrin complexation enhances the solubility of poorly soluble drugs but is solvent-intensive and environmentally unfavorable. This study evaluated solvent-free hot-melt extrusion (HME) for forming cyclodextrin inclusion complexes to improve the solubility and dissolution of ibuprofen (IBU). Molecular docking confirmed IBU’s hosting in Hydroxypropyl-β-cyclodextrin (HPβ-CD), while phase solubility revealed its complex stoichiometry and stability. In addition, an 11 mm twin-screw co-rotating extruder with PVP VA-64 as an auxiliary substance aided the complex formation and extrusion. Using QbD and the Box–Behnken design, we studied variables (barrel temperature, screw speed, and polymer concentration) and their impact on solubility and dissolution. The high polymer concentration and high screw speeds positively affected the dependent variables. However, higher temperatures had a negative effect. The lowest barrel temperature set near the Tg of the polymer, when combined with high polymer concentrations, resulted in high torques in HME and halted the extrusion process. Therefore, the temperature and polymer concentration should be selected to provide sufficient melt viscosities to aid the complex formation and extrusion process. Studies such as DSC and XRD revealed the amorphous conversion of IBU, while the inclusion complex formation was demonstrated by ATR and NMR studies. The dissolution of ternary inclusion complexes (TIC) produced from HME was found to be ≥85% released within 30 min. This finding implied the high solubility of IBU, according to the US FDA 2018 guidance for highly soluble compounds containing immediate-release solid oral dosage forms. Overall, the studies revealed the effect of various process parameters on the formation of CD inclusion complexes via HME. Full article
(This article belongs to the Special Issue Recent Advances in Cyclodextrins-Based Drug Delivery Systems)
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Review

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15 pages, 1229 KiB  
Review
A Systematic Review of Clinical Trials on the Efficacy and Safety of CRLX101 Cyclodextrin-Based Nanomedicine for Cancer Treatment
by Ana Serrano-Martínez, Desirée Victoria-Montesinos, Ana María García-Muñoz, Pilar Hernández-Sánchez, Carmen Lucas-Abellán and Rebeca González-Louzao
Pharmaceutics 2023, 15(7), 1824; https://doi.org/10.3390/pharmaceutics15071824 - 26 Jun 2023
Cited by 2 | Viewed by 1211
Abstract
CRLX101 is a cyclodextrin-based nanopharmaceutical designed to improve the delivery and efficacy of the anti-cancer drug camptothecin. Cyclodextrins have unique properties that can enhance drug solubility, stability, and bioavailability, making them an attractive option for drug delivery. The use of cyclodextrin-based nanoparticles can [...] Read more.
CRLX101 is a cyclodextrin-based nanopharmaceutical designed to improve the delivery and efficacy of the anti-cancer drug camptothecin. Cyclodextrins have unique properties that can enhance drug solubility, stability, and bioavailability, making them an attractive option for drug delivery. The use of cyclodextrin-based nanoparticles can potentially reduce toxicity and increase the therapeutic index compared to conventional chemotherapy. CRLX101 has shown promise in preclinical studies, demonstrating enhanced tumor targeting and prolonged drug release. This systematic review followed PRISMA guidelines, assessing the efficacy and toxicity of CRLX101 in cancer treatment using clinical trials. Studies from January 2010 to April 2023 were searched in PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, using specific search terms. The risk of bias was assessed using ROBINS-I and Cochrane risk-of-bias tools. After screening 6018 articles, 9 were included in the final review. These studies, conducted between 2013 and 2022, focused on patients with advanced or metastatic cancer resistant to standard therapies. CRLX101 was often combined with other therapeutic agents, resulting in improvements such as increased progression-free survival and clinical benefit rates. Toxicity was generally manageable, with common adverse events including fatigue, nausea, and anemia. Full article
(This article belongs to the Special Issue Recent Advances in Cyclodextrins-Based Drug Delivery Systems)
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