Novel Anticancer Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 18733

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Guest Editor
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia
Interests: human and veterinary pharmaceuticals; advanced drug delivery; cancer; infection; 3D printing
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Guest Editor
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences (MCOPS), Manipal University, Manipal, Karnataka 576104, India
Interests: controlled drug delivery; polymeric nanoparticles; liposomes; nanoemulsions; lipid nanoparticles; chronotherapeutics; solubility enhancement
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is one of the leading causes of death worldwide, and there is a constant rise in cancer cases day by day. According to World Cancer Report, by the year 2020 there may be 15 million new cases of cancer. Currently, the cancer treatment strategies include surgery, chemotherapy, and radiotherapy, and it is widely known that these therapies inhibit the growth also of normal cells and are associated with high toxicity. The area of cancer therapy is a highly dynamic field, and breakthrough advancements are being made to develop novel strategies. Several strategies, such as receptor-based targeting, intracellular drug targeting, stimuli-based drug release, magnetic drug targeting, ultrasound-mediated drug delivery, gene delivery, and cancer stem cell therapy, have added new dimensions to the treatment approaches. These strategies aid in the selective detection and killing of tumour cells with minimal side effects and may be useful to reduce the chances of multidrug resistance, thus improving the quality of life of patients.

This Special Issue of Pharmaceutics focuses on "Novel Anticancer Drug Delivery Systems" which could help solve issues related to side effects, high toxicities, and drug resistance of anticancer drugs. Articles concerning all aspects of novel anticancer drug delivery systems, especially, new materials, strategies, and synthetic approaches are welcome for this Special Issue.

Prof. Dr. Sanjay Garg
Dr. Usha Y. Nayak
Guest Editors

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Keywords

  • cancer treatment
  • gene therapy
  • targeted therapy
  • stimuli-based release
  • stem cell therapy

Published Papers (5 papers)

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Research

17 pages, 3185 KiB  
Article
Doxorubicin-Loaded Delta Inulin Conjugates for Controlled and Targeted Drug Delivery: Development, Characterization, and In Vitro Evaluation
by Lixin Wang, Yunmei Song, Ankit Parikh, Paul Joyce, Rosa Chung, Liang Liu, Franklin Afinjuomo, John D. Hayball, Nikolai Petrovsky, Thomas G. Barclay and Sanjay Garg
Pharmaceutics 2019, 11(11), 581; https://doi.org/10.3390/pharmaceutics11110581 - 6 Nov 2019
Cited by 21 | Viewed by 4043
Abstract
Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to [...] Read more.
Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid–labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was efficiently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery. Full article
(This article belongs to the Special Issue Novel Anticancer Drug Delivery Systems)
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21 pages, 3641 KiB  
Article
Magnetoliposomes Containing Calcium Ferrite Nanoparticles for Applications in Breast Cancer Therapy
by Daniela S. M. Pereira, Beatriz D. Cardoso, Ana Rita O. Rodrigues, Carlos O. Amorim, Vítor S. Amaral, Bernardo G. Almeida, Maria-João R. P. Queiroz, Olga Martinho, Fátima Baltazar, Ricardo C. Calhelha, Isabel C. F. R. Ferreira, Paulo J. G. Coutinho and Elisabete M. S. Castanheira
Pharmaceutics 2019, 11(9), 477; https://doi.org/10.3390/pharmaceutics11090477 - 14 Sep 2019
Cited by 25 | Viewed by 4512
Abstract
Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new [...] Read more.
Magnetoliposomes containing calcium ferrite (CaFe2O4) nanoparticles were developed and characterized for the first time. CaFe2O4 nanoparticles were covered by a lipid bilayer or entrapped in liposomes forming, respectively, solid or aqueous magnetoliposomes as nanocarriers for new antitumor drugs. The magnetic nanoparticles were characterized by UV/Visible absorption, XRD, HR-TEM, and SQUID, exhibiting sizes of 5.2 ± 1.2 nm (from TEM) and a superparamagnetic behavior. The magnetoliposomes were characterized by DLS and TEM. The incorporation of two new potential antitumor drugs (thienopyridine derivatives) specifically active against breast cancer in these nanosystems was investigated by fluorescence emission and anisotropy. Aqueous magnetoliposomes, with hydrodynamic diameters around 130 nm, and solid magnetoliposomes with sizes of ca. 170 nm, interact with biomembranes by fusion and are able to transport the antitumor drugs with generally high encapsulation efficiencies (70%). These fully biocompatible drug-loaded magnetoliposomes can be promising as therapeutic agents in future applications of combined breast cancer therapy. Full article
(This article belongs to the Special Issue Novel Anticancer Drug Delivery Systems)
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17 pages, 4014 KiB  
Article
Systematic Meta-Analysis Identifies Co-Expressed Kinases and GPCRs in Ovarian Cancer Tissues Revealing a Potential for Targeted Kinase Inhibitor Delivery
by Hugo Albrecht and Eric Kübler
Pharmaceutics 2019, 11(9), 454; https://doi.org/10.3390/pharmaceutics11090454 - 2 Sep 2019
Cited by 6 | Viewed by 2900
Abstract
The use of many anticancer drugs is problematic due to severe adverse effects. While the recent clinical launch of several kinase inhibitors led to tremendous progress, these targeted agents tend to be of non-specific nature within the kinase target class. Moreover, target mediated [...] Read more.
The use of many anticancer drugs is problematic due to severe adverse effects. While the recent clinical launch of several kinase inhibitors led to tremendous progress, these targeted agents tend to be of non-specific nature within the kinase target class. Moreover, target mediated adverse effects limit the exploitation of some very promising kinase targets, including mitotic kinases. A future strategy will be the development of nanocarrier-based systems for the active delivery of kinase inhibitors using cancer specific surface receptors. The G-protein-coupled-receptors (GPCRs) represent the largest cell surface receptor family and some members are known to be frequently overexpressed in various cancer types. In the presented study, we used ovarian cancer tissues as an example to systematically identify concurrently overexpressed GPCRs and kinases. The rationale of this approach will guide the future design of nanoparticles, which will dock to GPCRs on cancer cells via specific ligands and deliver anticancer compounds after receptor mediated internalization. In addition to this, the approach is expected to be most effective by matching the inhibitor profiles of the delivered kinase inhibitors to the observed kinase gene expression profiles. We validated the suggested strategy in a meta-analysis, revealing overexpression of selected GPCRs and kinases in individual samples of a large ovarian cancer data set. The presented data demonstrate a large untapped potential for personalized cancer therapy using high-end targeted nanopharmaceuticals with kinase inhibitors. Full article
(This article belongs to the Special Issue Novel Anticancer Drug Delivery Systems)
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20 pages, 11106 KiB  
Article
Short and Long-Term Effects of the Exposure of Breast Cancer Cell Lines to Different Ratios of Free or Co-Encapsulated Liposomal Paclitaxel and Doxorubicin
by Marina Santiago Franco, Marjorie Coimbra Roque and Mônica Cristina Oliveira
Pharmaceutics 2019, 11(4), 178; https://doi.org/10.3390/pharmaceutics11040178 - 11 Apr 2019
Cited by 18 | Viewed by 3365
Abstract
Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to [...] Read more.
Background: Associating paclitaxel (PTX) to doxorubicin (DXR) is one of the main chemotherapy strategies for breast cancer (BC) management. Protocols currently available consist in administering both drugs on their maximum tolerated dose, not taking into account the possible differences in efficacy due to their combination ratio. In the present study, the short and long-term cytotoxic effects as well as migratory effects of PTX, DXR, and its combinations at 10:1; 1:1 and 1:10 PTX:DXR molar ratios either free or co-encapsulated in liposomes were evaluated against three human BC cell lines (MDA-MB-231, MCF-7, and SKBR-3). Method: The MTT assay was used to screen for synergy or antagonism between PTX and DXR and the combination index value was calculated using the CalcuSyn software. Nuclear morphological alterations were evaluated by staining the cells with Hoescht 33342. The investigation of senescence and clonogenicity of BC cell lines exposed to different treatments was also studied. In addition, the ability of these cells to migrate was assessed. Results: Taken together, the results presented herein allow us to suggest that there is no benefit in enhancing the PTX concentration above that of DXR in the combination for any of the three cell lines tested. Conclusion: The developed liposomes co-encapsulating PTX and DXR in different molar ratios retained the biological properties of the mixture of free drugs and are valuable for planning new therapeutic strategies. Full article
(This article belongs to the Special Issue Novel Anticancer Drug Delivery Systems)
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7 pages, 1334 KiB  
Article
One-Pot Synthesis of Epirubicin-Capped Silver Nanoparticles and Their Anticancer Activity against Hep G2 Cells
by Jun Ding, Guilin Chen, Guofang Chen and Mingquan Guo
Pharmaceutics 2019, 11(3), 123; https://doi.org/10.3390/pharmaceutics11030123 - 15 Mar 2019
Cited by 33 | Viewed by 3278
Abstract
Epirubicin-capped silver nanoparticles (NPs) were synthesized through a one-pot method by using epirubicin as both the functional drug and the reducing agent of Ag+ to Ag0. The preparation process was accomplished in 1 h. In addition, the obtained epirubicin-capped silver [...] Read more.
Epirubicin-capped silver nanoparticles (NPs) were synthesized through a one-pot method by using epirubicin as both the functional drug and the reducing agent of Ag+ to Ag0. The preparation process was accomplished in 1 h. In addition, the obtained epirubicin-capped silver nanoparticle was characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and infrared spectroscopy. The results showed that a layer of polymer epirubicin had formed around the silver nanoparticle, which was 30-40 nm in diameter. We further investigated the antitumor activity of the prepared epirubicin-capped silver nanoparticle, and the half maximal inhibitory concentration (IC50) against Hep G2 cells was 1.92 μg/mL, indicating a good antitumor property of the nanoparticle at low dosage. Full article
(This article belongs to the Special Issue Novel Anticancer Drug Delivery Systems)
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