Cyclodextrin-Based Drug Delivery System and Its Pharmaceutical and Biomedical Application 2024

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 15 August 2024 | Viewed by 3559

Special Issue Editors


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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Interests: drug delivery; drug/cyclodextrin inclusion complexes; polymeric nanoparticles; cancer diseases; antimicrobial drugs; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Interests: drug delivery; cyclodextrin; drug/cyclodextrin inclusion complexes; nanoparticles; nanostructures; supramolecular chemistry; anticancer therapy; antibacterial therapy; neurodegenerative disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmaceuticals is planning to publish a Special Issue titled “Cyclodextrin-Based Drug Delivery System and its Pharmaceutical and Biomedical Application”, and I am cordially inviting you to contribute your communications, research articles or high-quality review papers.  

Cyclodextrins have long received a great deal of interest from the scientific community for their versatility and possibile applications in various fields of science. They are cyclic oligosaccharides produced by the enzymatic degradation of starch and characterized by a hydrophobic internal cavity and a hydrophilic external surface. This architecture allows for the possibility of encapsulating various substances, thus improving their physicochemical properties. Cyclodextrins are the pioneers of supramolecular carriers and are used in the pharmaceutical field for their ability to solubilize lipophilic drugs, enhancing their biological effects. Mixed supramolecular carriers, consisting of cyclodextrins in polymeric nanoparticles or cyclodextrins in liposomes, exhibit improved encapsulation parameters and controlled drug release, compared to the corresponding carrier without macrocycles. Different chemical modifications can be made on the free hydroxyl groups of cyclodextrins, producing derivatives with greater water solubility than native cyclodextrins and in some cases with excellent mucoadhesive properties able to increase drug permeation through the mucosae. Nanostructured systems based on polymeric cyclodextrins show low toxicity, good bioavailability and biodegradability, and can be used in a wide range of biomedical applications, from erodible hydrogels for regenerative medicine to targeted drug and gene delivery.

This Special Issue intends to host research and review papers on the development of novel cyclodextrin-based drug delivery systems performed in the scientific areas of pharmaceutical technology, chemistry, physics, and biology. Areas of interest include, but are not limited to, drug–cyclodextrin interactions, cyclodextrin-based nanoparticles, cyclodextrin in liposomes, cyclodextrins as drugs, cyclodextrin dimers and polymers, biological in vitro/ex vivo/in vivo evaluation of cyclodextrin-based formulations, cyclodextrin–cell interactions, cyclodextrin-based hydrogels, and regenerative medicine.

Prof. Dr. Cinzia Anna Ventura
Dr. Federica De Gaetano
Guest Editors

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Keywords

  • drug delivery
  • inclusion complexes
  • polymeric cyclodextrins
  • nanostructurated carriers
  • polyrotaxanes
  • nanosponges
  • chemical–physical characterization
  • in vitro/ex vivo/in vivo evaluation
  • theranostic
  • regenerative medicine
  • gene delivery

Published Papers (3 papers)

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Research

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21 pages, 3529 KiB  
Article
Investigation on the Combined Effect of Hydroxypropyl Beta-Cyclodextrin (HPβCD) and Polysorbate in Monoclonal Antibody Formulation
by Jiayi Huang, Shiqi Hong, Lucas Yuan Hao Goh, Hailong Zhang, Tao Peng, Keat Theng Chow, Rajeev Gokhale and Vinod Tuliani
Pharmaceuticals 2024, 17(4), 528; https://doi.org/10.3390/ph17040528 - 19 Apr 2024
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Abstract
Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations [...] Read more.
Monoclonal antibodies require careful formulation due to their inherent stability limitations. Polysorbates are commonly used to stabilize mAbs, but they are prone to degradation, which results in unwanted impurities. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin) has functioned as a stable stabilizer for protein formulations in our previous research. The current study investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein–protein interactions by HPβCD. In bevacizumab formulations, the subvisible particle counts per 0.4 mL of samples in commercial formulations vs. formulations containing both HPβCD and polysorbates subjected to distinct stressors were as follows: agitation, 87,308 particles vs. 15,350 particles; light, 25,492 particles vs. 6765 particles; and heat, 1775 particles vs. 460 particles. Isothermal titration calorimetry (ITC) measurement indicated a weak interaction between PS 80 and HPβCD, with a KD value of 74.7 ± 7.5 µM and binding sites of 5 × 10–3. Surface tension measurements illustrated that HPβCD enhanced the surface activity of polysorbates. The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry. Full article
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0 pages, 4248 KiB  
Article
Chrysin Directing an Enhanced Solubility through the Formation of a Supramolecular Cyclodextrin–Calixarene Drug Delivery System: A Potential Strategy in Antifibrotic Diabetes Therapeutics
by Anca Hermenean, Eleftheria Dossi, Alex Hamilton, Maria Consiglia Trotta, Marina Russo, Caterina Claudia Lepre, Csilla Sajtos, Ágnes Rusznyák, Judit Váradi, Ildikó Bácskay, István Budai, Michele D’Amico and Ferenc Fenyvesi
Pharmaceuticals 2024, 17(1), 107; https://doi.org/10.3390/ph17010107 - 12 Jan 2024
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Abstract
Calixarene 0118 (OTX008) and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications but require an effective delivery system to overcome their low solubility and bioavailability. Sulfobutylated β-cyclodextrin (SBECD) was evaluated for its ability to increase the solubility of [...] Read more.
Calixarene 0118 (OTX008) and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications but require an effective delivery system to overcome their low solubility and bioavailability. Sulfobutylated β-cyclodextrin (SBECD) was evaluated for its ability to increase the solubility of CHR by forming a ternary complex with OTX008. The resulting increase in solubility and the mechanisms of complex formation were identified through phase-solubility studies, while dynamic light-scattering assessed the molecular associations within the CHR-OTX008-SBECD system. Nuclear magnetic resonance, differential scanning calorimetry, and computational studies elucidated the interactions at the molecular level, and cellular assays confirmed the system’s biocompatibility. Combining SBECD with OTX008 enhances CHR solubility more than using SBECD alone by forming water-soluble molecular associates in a ternary complex. This aids in the solubilization and delivery of CHR and OTX008. Structural investigations revealed non-covalent interactions essential to complex formation, which showed no cytotoxicity in hyperglycemic in vitro conditions. A new ternary complex has been formulated to deliver promising antifibrotic agents for diabetic complications, featuring OTX008 as a key structural and pharmacological component. Full article
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Review

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18 pages, 601 KiB  
Review
Cyclodextrins for the Delivery of Bioactive Compounds from Natural Sources: Medicinal, Food and Cosmetics Applications
by Stamatia Christaki, Eleni Spanidi, Eleni Panagiotidou, Sophia Athanasopoulou, Anastasia Kyriakoudi, Ioannis Mourtzinos and Konstantinos Gardikis
Pharmaceuticals 2023, 16(9), 1274; https://doi.org/10.3390/ph16091274 - 8 Sep 2023
Cited by 3 | Viewed by 1545
Abstract
Cyclodextrins have gained significant and established attention as versatile carriers for the delivery of bioactive compounds derived from natural sources in various applications, including medicine, food and cosmetics. Their toroidal structure and hydrophobic cavity render them ideal candidates for encapsulating and solubilizing hydrophobic [...] Read more.
Cyclodextrins have gained significant and established attention as versatile carriers for the delivery of bioactive compounds derived from natural sources in various applications, including medicine, food and cosmetics. Their toroidal structure and hydrophobic cavity render them ideal candidates for encapsulating and solubilizing hydrophobic and poorly soluble compounds. Most medicinal, food and cosmetic ingredients share the challenges of hydrophobicity and degradation that can be effectively addressed by various cyclodextrin types. Though not new or novel—their first applications appeared in the market in the 1970s—their versatility has inspired numerous developments, either on the academic or industrial level. This review article provides an overview of the ever-growing applications of cyclodextrins in the delivery of bioactive compounds from natural sources and their potential application benefits. Full article
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