Submit to Pharmaceutics Review for Pharmaceutics Propose a Special Issue

Journal Menu

Journal Browser

Cyclodextrin-Based Delivery Systems for Anticancer Drugs

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

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 (10 November 2022) | Viewed by 20298

Share This Special Issue

Special Issue Editors

Dr. Cristina Trandafirescu

E-Mail Website
Guest Editor

1. Departament of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy Timisoara, 2nd EftimieMurgu Sq., 300041 Timişoara, Romania
2. Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, 2 Eftimie Murgu Street, 300041 Timisoara, Romania
Interests: supramolecular compounds; anticancer therapy; targeted therapy
Special Issues, Collections and Topics in MDPI journals

Dr. Iulia Pinzaru

E-Mail Website
Guest Editor

1. Department of Toxicology and Drug Industry, Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy Timişoara, 2 Eftimie Murgu Street, 300041 Timişoara, Romania
2. Research Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timișoara, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
Interests: toxicology; nanoparticles; natural and synthetic drugs; natural compounds; derivatization
Special Issues, Collections and Topics in MDPI journals

Dr. Denisa Laura Cîrcioban

E-Mail Website
Guest Editor

Department of Analytical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania
Interests: stability of drugs and compounds with potential biological activity; instrumental analysis of drugs as pure APIs and in pharmaceutical dosage forms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Malignant diseases are one of the most powerful diseases of the current century, representing a major cause of death globally. Even if anticancer research and drug discovery continuously increase the therapeutic arsenal, chemotherapy has many drawbacks due to poor bioavailability, side effects, drug resistance, and target specificity.

Besides the screening of synthetic molecules with anticancer potential, natural compounds represent a valuable alternative to the limitations of conventional chemotherapy. Natural compounds also face drawbacks that limit their utilization, such as poor water solubility, low dissolution rate, bioavailability, and increased sensitivity to degradation and inactivation.

Cyclodextrins are, nowadays, considered valuable pharmaceutical excipients due to their ability to partly or completely include a drug molecule, thus improving the unfavorable physicochemical and the biological properties of the hosted molecule. Moreover, the protection and especially the controlled release of various organic compounds are carried out almost exclusively by encapsulation.

Currently, the development of improved formulations based on natural and synthetic compounds with increased bioavailability and stability, along with dose reduction and the reduction in adverse effects, represent topical issues.

This Special Issue will bring together recent data regarding the role of cyclodextrins in developing improved delivery systems containing anticancer compounds. We invite reviews, original research, meta-analyses, short communications, and study designs on all aspects of the influence of cyclodextrin complexation on the physicochemical and biological properties of anticancer drugs.

Dr. Cristina Trandafirescu
Dr. Iulia Pinzaru
Dr. Denisa Laura Cîrcioban
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
delivery systems
anticancer compounds
natural compounds
bioavailability
stability

Related Special Issue

Cyclodextrin-Based Delivery Systems for Anticancer Drugs, 2nd Edition in Pharmaceutics

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

11 pages, 1795 KiB

Open AccessArticle

Hyaluronan-Cyclodextrin Conjugates as Doxorubicin Delivery Systems

by Noemi Bognanni, Maurizio Viale, Luana La Piana, Simone Strano, Rosaria Gangemi, Cinzia Lombardo, Maria Teresa Cambria and Graziella Vecchio

Pharmaceutics 2023, 15(2), 374; https://doi.org/10.3390/pharmaceutics15020374 - 21 Jan 2023

Cited by 3 | Viewed by 2013

Abstract

In the last years, nanoparticles based on cyclodextrins have been widely investigated for the delivery of anticancer drugs. In this work, we synthesized nanoparticles with a hyaluronic acid backbone functionalized with cyclodextrins under green conditions. We functionalized hyaluronic acid with two different molecular weights (about 11 kDa and 45 kDa) to compare their behavior as doxorubicin delivery systems. We found that the new hyaluronan-cyclodextrin conjugates increased the water solubility of doxorubicin. Moreover, we tested the antiproliferative activity of doxorubicin in the presence of the new cyclodextrin polymers in SK-N-SH and SK-N-SH-PMA (over-expressing CD44 receptor) cancer cells. We found that hyaluronan-cyclodextrin conjugates improved the uptake and antiproliferative activity of doxorubicin in the SK-N-SH-PMA compared to the SK-N-SH cell line at the ratio 8/1 doxorubicin/polymer. Notably, the system based on hyaluronan (45 kDa) was more effective as a drug carrier and significantly reduced the IC₅₀ value of doxorubicin by about 56%. We also found that hyaluronic acid polymers determined an improved antiproliferative activity of doxorubicin (IC₅₀ values are on average reduced by about 70% of free DOXO) in both cell lines at the ratio 16/1 doxorubicin/polymer. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

23 pages, 5624 KiB

Open AccessArticle

Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer

by Safiye Akkın, Gamze Varan, Anıl Işık, Sibel Gökşen, Elif Karakoç, Milo Malanga, Güneş Esendağlı, Petek Korkusuz and Erem Bilensoy

Pharmaceutics 2023, 15(2), 314; https://doi.org/10.3390/pharmaceutics15020314 - 17 Jan 2023

Cited by 1 | Viewed by 1972

Abstract

Chemotherapy is the most used method after surgery in the treatment of colon cancer. Cancer cells escape the recognition mechanism of immune system cells to survive and develop chemoresistance. Therefore, the use of immunotherapy in combination with chemotherapy can increase the effectiveness of the treatment. Nanoparticles have been used clinically to increase the accumulation of therapeutics in target tissues and reduce toxicity. In this paper, nanoplexes were formed via cationic cyclodextrin polymer, 5-Fluorouracil, and Interleukin-2 based on the opposite charge interaction of macromolecules without undergoing any structural changes or losing the biological activity of Interleukin-2. Anticancer activities of nanoplexes were determined in two-dimensional and three-dimensional cell culture setups. The dual drug-loaded cyclodextrin nanoplexes diffused deeper into the spheroids and accelerated apoptosis when compared with 5-FU solutions. In the colorectal tumor-bearing animal model, survival rate, antitumor activity, metastasis, and immune response parameters were assessed using a cyclodextrin derivative, which was found to be safe based on the ALT/AST levels in healthy mice. Histomorphometric analysis showed that the groups treated with the nanoplex formulation had significantly fewer initial tumors and lung foci when compared with the control. The dual drug-loaded nanoplex could be a promising drug delivery technique in the immunochemotherapy of colorectal cancer. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

20 pages, 4051 KiB

Open AccessArticle

Carvacrol and HP-β-Cyclodextrin Complexes: Extensive Characterization and Potential Cytotoxic Effect in Human Colorectal Carcinoma Cells

by María Isabel Rodríguez-López, María Teresa Mercader-Ros, Alfonso Pérez-Garrido, Horacio Pérez-Sánchez, José Antonio Pellicer, Carmen Lucas-Abellán, Silvia Montoro-García, María Josefa Yáñez-Gascón, Ángel Gil-Izquierdo, Estrella Núñez-Delicado and José Antonio Gabaldón

Pharmaceutics 2022, 14(12), 2638; https://doi.org/10.3390/pharmaceutics14122638 - 29 Nov 2022

Cited by 1 | Viewed by 1599

Abstract

The aim of this study was to obtain solid carvacrol-cyclodextrin (CD) complexes for use in the pharmaceutical industry. To this end, the complexation of carvacrol at different pH values was studied in detail, to determine the type of CD and the reaction environment that supported the highest amount of encapsulated carvacrol. Evidence of the capability of hydroxypropyl-β-cyclodextrins (HP-β-CD) to form inclusion complexes with carvacrol (K_C = 5042 ± 176 L mol⁻¹) and more high complexation efficiency (2.824) was demonstrated for HP-β-CDs using two different energy sources, ultrasound (US) (K_C = 8129 ± 194 L mol⁻¹ 24 h) and microwave irradiation (MWI) (K_C = 6909 ± 161 L mol⁻¹), followed by spraying the resulting solution in a spray dryer. To confirm complex formation, the complexes were characterized using various instrumental methods to corroborate the carvacrol incorporation into the hydrophobic cavity of HP-β-CD. The obtained carvacrol solid complexes were analyzed by 1H nuclear magnetic resonance (¹H-NMR) and 2D nuclear magnetic resonance (ROSEY), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and Fourier transform infrared spectroscopy (FTIR) characterization. The structures of the resulting complexes were also characterized by molecular modeling. Furthermore, 1 mM HP-β-CD-carvacrol complex has been shown to reduce cell proliferation in HCT-116 colorectal cancer cells by 43%, much more than in a healthy lung fibroblast MRC-5 cell line (11%). Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

18 pages, 3182 KiB

Open AccessArticle

A β-Cyclodextrin-Based Nanoparticle with Very High Transfection Efficiency Unveils siRNA-Activated TLR3 Responses in Human Prostate Cancer Cells

by Cristina de la Torre, Pablo Játiva, Inmaculada Posadas, Darío Manzanares, José L. Jiménez Blanco, Carmen Ortiz Mellet, José Manuel García Fernández and Valentín Ceña

Pharmaceutics 2022, 14(11), 2424; https://doi.org/10.3390/pharmaceutics14112424 - 09 Nov 2022

Cited by 4 | Viewed by 1943

Abstract

Synthetic double-stranded small interfering RNAs (siRNAs) mimic interference RNAs (RNAi) and can bind target mRNAs with a high degree of specificity, leading to selective knockdown of the proteins they encode. However, siRNAs are very labile and must be both protected and transported by nanoparticles to be efficiently delivered into cells. In this work, we used a Janus-type polycationic amphiphilic β-cyclodextrin derivative to efficiently transfect siRNAs targeting mRNAs encoding mitogen-activated protein kinase (p42-MAPK) or Ras homolog enriched in brain (Rheb) into different cancer cell lines as well as astrocytes. We took advantage of this high transfection efficiency to simultaneously knock down p42-MAPK and Rheb to boost docetaxel (DTX)-mediated toxicity in two human prostate cancer cell lines (LNCaP and PC3). We found that double knockdown of p42-MAPK and Rheb increased DTX-toxicity in LNCaP but not in PC3 cells. However, we also observed the same effect when scramble siRNA was used, therefore pointing to an off-target effect. Indeed, we found that the siRNA we used in this work induced toll-like receptor 3 activation, leading to β-interferon production and caspase activation. We believe that this mechanism could be very useful as a general strategy to elicit an immune response against prostate cancer cells. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

28 pages, 11304 KiB

Open AccessArticle

β-Cyclodextrin-Based Nanosponges Inclusion Compounds Associated with Gold Nanorods for Potential NIR-II Drug Delivery

by Sebastián Salazar Sandoval, Elizabeth Cortés-Adasme, Eduardo Gallardo-Toledo, Ingrid Araya, Freddy Celis, Nicolás Yutronic, Paul Jara and Marcelo J. Kogan

Pharmaceutics 2022, 14(10), 2206; https://doi.org/10.3390/pharmaceutics14102206 - 17 Oct 2022

Cited by 3 | Viewed by 2254

Abstract

This article describes the synthesis and characterization of two nanocarriers consisting of β-cyclodextrin-based nanosponges (NSs) inclusion compounds (ICs) and gold nanorods (AuNRs) for potential near-infrared II (NIR-II) drug-delivery systems. These nanosystems sought to improve the stability of two drugs, namely melphalan (MPH) and curcumin (CUR), and to trigger their photothermal release after a laser irradiation stimulus (1064 nm). The inclusion of MPH and CUR inside each NS was confirmed by field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, Fourier transform infrared spectroscopy, (FT-IR) differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and proton nuclear magnetic resonance (¹H-NMR). Furthermore, the association of AuNRs with both ICs was confirmed by FE-SEM, energy-dispersive spectroscopy (EDS), TEM, dynamic light scattering (DLS), ζ-potential, and UV–Vis. Moreover, the irradiation assays demonstrated the feasibility of the controlled-photothermal drug release of both MPH and CUR in the second biological window (1000–1300 nm). Finally, MTS assays depicted that the inclusion of MPH and CUR inside the cavities of NSs reduces the effects on mitochondrial activity, as compared to that observed in the free drugs. Overall, these results suggest the use of NSs associated with AuNRs as a potential technology of controlled drug delivery in tumor therapy, since they are efficient and non-toxic materials. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

14 pages, 3469 KiB

Open AccessArticle

Tetraethylenepentamine-Coated β Cyclodextrin Nanoparticles for Dual DNA and siRNA Delivery

by Chi-Hsien Liu, Pei-Yin Shih, Cheng-Han Lin, Yi-Jun Chen, Wei-Chi Wu and Chun-Chao Wang

Pharmaceutics 2022, 14(5), 921; https://doi.org/10.3390/pharmaceutics14050921 - 23 Apr 2022

Cited by 4 | Viewed by 2113

Abstract

Nucleic acid reagents, including plasmid-encoded genes and small interfering RNA (siRNA), are promising tools for validating gene function and for the development of therapeutic agents. Native β-cyclodextrins (BCDs) have limited efficiency in gene delivery due to their instable complexes with nucleic acid. We hypothesized that cationic BCD nanoparticles could be an efficient carrier for both DNA and siRNA. Tetraethylenepentamine-coated β-cyclodextrin (TEPA-BCD) nanoparticles were synthesized, characterized, and evaluated for targeted cell delivery of plasmid DNA and siRNA. The cationic TEPA coating provided ideal zeta potential and effective nucleic acid binding ability. When transfecting plasmid encoding green fluorescent protein (GFP) by TEPA-BCD, excellent GFP expression could be achieved in multiple cell lines. In addition, siRNA transfected by TEPA-BCD suppressed target GFP gene expression. We showed that TEPA-BCD internalization was mediated by energy-dependent endocytosis via both clathrin-dependent and caveolin-dependent endocytic pathways. TEPA-BCD nanoparticles provide an effective means of nucleic acid delivery and can act as potential carriers in future pharmaceutical application. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

19 pages, 3718 KiB

Open AccessArticle

Polymerized β-Cyclodextrin-Based Injectable Hydrogel for Sustained Release of 5-Fluorouracil/Methotrexate Mixture in Breast Cancer Management: In Vitro and In Vivo Analytical Validations

by Saud Almawash, Mohamed A. El Hamd and Shaaban K. Osman

Pharmaceutics 2022, 14(4), 817; https://doi.org/10.3390/pharmaceutics14040817 - 08 Apr 2022

Cited by 9 | Viewed by 1816

Abstract

An inclusion complexation, between polymerized β-cyclodextrin and cholesterol end-capping branched polyethylene glycol, was utilized for constructing a self-assembled hydrogel. The physicochemical properties, the in vitro release profiles of 5-Fluorouracil/methotrexate (anticancer drugs), and the surface morphology of the resulting hydrogel were studied. Moreover, in vivo studies were carried out on female rats bearing breast cancer. The results revealed that the prepared systems were white in color, rubbery, and homogenous. The in vitro release studies showed an efficient ability of the modified system for drug loading and release in a sustained release manner for 14 days. The surface morphology was spongy porous. Moreover, the tumors’ healing was indicated from the analysis of tumor volume, plasma tumor markers, and histopathological analysis, compared to the controlled rats. The pharmacokinetic parameters appeared significant differences (p < 0.05) in the C_max and T_max of the medicated hydrogel samples, as compared with sole or combined saline-injected samples. The whole AUC of each drug in the medicated hydrogel samples was five-fold more than the mixture administrated in PBS. In conclusion, the proposed work delivered a hydrogel system that has a convenient ability for localized sustained release of breast cancer management. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 1515 KiB

Open AccessReview

An Updated Overview of Cyclodextrin-Based Drug Delivery Systems for Cancer Therapy

by Dan Nicolae Păduraru, Adelina-Gabriela Niculescu, Alexandra Bolocan, Octavian Andronic, Alexandru Mihai Grumezescu and Rodica Bîrlă

Pharmaceutics 2022, 14(8), 1748; https://doi.org/10.3390/pharmaceutics14081748 - 22 Aug 2022

Cited by 24 | Viewed by 3604

Abstract

Encompassing a group of complex and heterogeneous diseases, cancer continues to be a challenge for patients and healthcare systems worldwide. Thus, it is of vital importance to develop advanced treatment strategies that could reduce the trends of cancer-associated morbidity and mortality rates. Scientists have focused on creating performant delivery vehicles for anti-cancer agents. Among the possible materials, cyclodextrins (CDs) attracted increasing interest over the past few years, leading to the emergence of promising anti-tumor nanomedicines. Tackling their advantageous chemical structure, ease of modification, natural origin, biocompatibility, low immunogenicity, and commercial availability, researchers investigated CD-based therapeutical formulations against many types of cancer. In this respect, in this paper, we briefly present the properties of interest of CDs for designing performant nanocarriers, further reviewing some of the most recent potential applications of CD-based delivery systems in cancer management. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Figure 1

16 pages, 4120 KiB

Open AccessReview

Cyclodextrin-Based Nanoplatforms for Tumor Phototherapy: An Update

by Xingjie Wu, Ying Chen, Qianqian Guo, Ling Tao, Yang Ding, Xianguang Ding and Xiangchun Shen

Pharmaceutics 2022, 14(7), 1375; https://doi.org/10.3390/pharmaceutics14071375 - 29 Jun 2022

Cited by 8 | Viewed by 1999

Abstract

Tumor phototherapies are light-mediated tumor treatment modalities, which usually refer to tumor photothermal therapy (PTT) and photodynamic therapy (PDT). Due to the outstanding spatial-temporal control over treatment through light irradiation, tumor phototherapies display extremely low side effects during treatment and are believed to be a tumor treatment method with a clinical translation potential. However, current tumor phototherapy nanoplatforms face obstacles, including light irradiation-induced skin burning, tumor hypoxia microenvironments, limited light penetration depth, et al. Therefore, one important research direction is developing a tumor phototherapy nanoplatform with multifunctionality and enhanced pharmacological effects to overcome the complexity of tumor treatment. On the other hand, cyclodextrins (CDs) are starch-originated circular oligosaccharides with negligible toxicity and have been used to form supermolecular nanostructures through a host–guest interaction between the inner cavity of CDs and functional biomolecules. In the past few years, numerous studies have focused on CD-based multifunctional tumor phototherapy nanoplatforms with an enhanced photoeffect, responsive morphological transformation, and elevated drug bioavailability. This review focuses on the preparation methods of CD-based tumor phototherapy nanoplatforms and their unique physiochemical properties for improving anti-tumor pharmacological efficacy. Full article

(This article belongs to the Special Issue Cyclodextrin-Based Delivery Systems for Anticancer Drugs)

► Show Figures

Journal Menu

Journal Browser

Cyclodextrin-Based Delivery Systems for Anticancer Drugs

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI