New Formulations for Cancer Therapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 66030

Special Issue Editors

Department of Pharmaceutics and Food Technology, Complutense University of Madrid, 28040 Madrid, Spain
Interests: nanomedicine; drug delivery systems; cancer; drug targeting; brain tumors; cannabinoids; microparticles; nanocarriers
Special Issues, Collections and Topics in MDPI journals
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain
Interests: nanomedicine; brain drug delivery; brain diseases; lipid nanocapsules; glioma; cannabinoids; tailored carriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The search for new formulations for cancer therapy to achieve improved bioavailability, efficacy, and safety constitutes the holy grail of anticancer drug research. In the fight against cancer, in recent years, researchers have put tremendous effort into evaluating the potential of drug carriers for this purpose. Noticeably, in the case of chemotherapeutic agents, drug encapsulation within carriers greatly contributes to reducing their frequent non-specific side effects that often lead to treatment discontinuation. Despite several carrier-based formulations achieving clinical translation, promising possibilities to develop second-generation formulations that address unmet advanced cancer-related medical challenges and ultimately enable the development of not only safer but also more efficacious drug delivery systems still remain. To this end, the harmonized integration of researchers from diverse multidisciplinary fields (namely, formulation scientists, cancer pathologists, clinical doctors) is required to foster the development of clinically translatable novel formulations for cancer therapy.

In this context, the aim of this Special Issue on “New Formulations for Cancer Therapy” is to gather papers addressing state-of-the-art trends and future directions in the development of clinically translatable carrier-based formulations for cancer treatment on topics ranging from rational design to relevant preclinical and/or clinical testing of efficacy, pharmacokinetics, and toxicity. Original research papers, communications, review articles, and opinions are welcome.

Prof. Dr. Ana Isabel Torres-Suárez
Prof. Dr. Juan Aparicio-Blanco
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

  • nanomedicine
  • cancer
  • anticancer drug delivery
  • implants
  • microcarriers
  • gene therapy
  • combination therapy
  • theranostics
  • targeted therapy
  • translational cancer nanomedicine

Related Special Issue

Published Papers (17 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

22 pages, 4508 KiB  
Article
Magnetoliposomes Based on Magnetic/Plasmonic Nanoparticles Loaded with Tricyclic Lactones for Combined Cancer Therapy
by Irina S. R. Rio, Ana Rita O. Rodrigues, Juliana M. Rodrigues, Maria-João R. P. Queiroz, R. C. Calhelha, Isabel C. F. R. Ferreira, Bernardo G. Almeida, Ana Pires, André M. Pereira, João P. Araújo, Elisabete M. S. Castanheira and Paulo J. G. Coutinho
Pharmaceutics 2021, 13(11), 1905; https://doi.org/10.3390/pharmaceutics13111905 - 10 Nov 2021
Cited by 7 | Viewed by 2347
Abstract
Liposome-like nanoarchitectures containing manganese ferrite nanoparticles covered or decorated with gold were developed for application in dual cancer therapy, combining chemotherapy and photothermia. The magnetic/plasmonic nanoparticles were characterized using XRD, UV/Visible absorption, HR-TEM, and SQUID, exhibiting superparamagnetic behavior at room temperature. The average [...] Read more.
Liposome-like nanoarchitectures containing manganese ferrite nanoparticles covered or decorated with gold were developed for application in dual cancer therapy, combining chemotherapy and photothermia. The magnetic/plasmonic nanoparticles were characterized using XRD, UV/Visible absorption, HR-TEM, and SQUID, exhibiting superparamagnetic behavior at room temperature. The average size of the gold-decorated nanoparticles was 26.7 nm for MnFe2O4 with 5–7 nm gold nanospheres. The average size of the core/shell nanoparticles was 28.8 nm for the magnetic core and around 4 nm for the gold shell. Two new potential antitumor fluorescent drugs, tricyclic lactones derivatives of thienopyridine, were loaded in these nanosystems with very high encapsulation efficiencies (higher than 98%). Assays in human tumor cell lines demonstrate that the nanocarriers do not release the antitumor compounds in the absence of irradiation. Moreover, the nanosystems do not cause any effect on the growth of primary (non-tumor) cells (with or without irradiation). The drug-loaded systems containing the core/shell magnetic/plasmonic nanoparticles efficiently inhibit the growth of tumor cells when irradiated with red light, making them suitable for a triggered release promoted by irradiation. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

15 pages, 69397 KiB  
Article
Nanoparticles Dual Targeting Both Myeloma Cells and Cancer-Associated Fibroblasts Simultaneously to Improve Multiple Myeloma Treatment
by Honglan Wang, Huiwen Liu, Chunyan Sun, Chunying Liu, Ting Jiang, Yanxue Yin, Aoshuang Xu, Zhiqing Pang, Bo Zhang and Yu Hu
Pharmaceutics 2021, 13(2), 274; https://doi.org/10.3390/pharmaceutics13020274 - 18 Feb 2021
Cited by 6 | Viewed by 2561
Abstract
Cancer-associated fibroblasts (CAFs) and myeloma cells could mutually drive myeloma progression, indicating that drug delivery to kill both CAFs and myeloma cells simultaneously could achieve better therapeutic benefits than to kill each cell type alone. Here, we designed a dual-targeting drug delivery system [...] Read more.
Cancer-associated fibroblasts (CAFs) and myeloma cells could mutually drive myeloma progression, indicating that drug delivery to kill both CAFs and myeloma cells simultaneously could achieve better therapeutic benefits than to kill each cell type alone. Here, we designed a dual-targeting drug delivery system by conjugating paclitaxel (PTX)-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles (NPs) with a cyclic peptide (CNPs-PTX) with a special affinity with platelet-derived growth factor/platelet-derived growth factor receptor (PDGFR-β) overexpressed on both CAFs and myeloma cells. Cellular uptake experiments revealed that the cyclic peptide modification on CNPs could significantly enhance CNPs uptake by both CAFs and myeloma cells compared with unmodified NPs. Cytotoxicity tests showed that CNPs-PTX was more toxic to both CAFs and myeloma cells compared with its counterpart PTX-loaded conventional NPs (NPs-PTX). In vivo imaging and biodistribution experiments showed that CNPs could abundantly accumulate in tumors and were highly co-localized with CAFs and myeloma cells. The in vivo anti-tumor experiments confirmed that the anti-myeloma efficacy of CNPs-PTX was significantly stronger than that of NPs-PTX and free drugs. In summary, it is the first time that a dual-targeting strategy was utilized in the field of myeloma treatment through targeting both CAFs and myeloma cells simultaneously, which harbors a high potential of clinical translation for myeloma treatment. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

15 pages, 2851 KiB  
Article
Endostatin Genetically Engineered Placental Mesenchymal Stromal Cells Carrying Doxorubicin-Loaded Mesoporous Silica Nanoparticles for Combined Chemo- and Antiangiogenic Therapy
by Paz de la Torre, Juan L. Paris, Miguel Fernández-de la Torre, María Vallet-Regí and Ana I. Flores
Pharmaceutics 2021, 13(2), 244; https://doi.org/10.3390/pharmaceutics13020244 - 10 Feb 2021
Cited by 3 | Viewed by 1926
Abstract
Combination therapies constitute a powerful tool for cancer treatment. By combining drugs with different mechanisms of action, the limitations of each individual agent can be overcome, while increasing therapeutic benefit. Here, we propose employing tumor-migrating decidua-derived mesenchymal stromal cells as therapeutic agents combining [...] Read more.
Combination therapies constitute a powerful tool for cancer treatment. By combining drugs with different mechanisms of action, the limitations of each individual agent can be overcome, while increasing therapeutic benefit. Here, we propose employing tumor-migrating decidua-derived mesenchymal stromal cells as therapeutic agents combining antiangiogenic therapy and chemotherapy. First, a plasmid encoding the antiangiogenic protein endostatin was transfected into these cells by nucleofection, confirming its expression by ELISA and its biological effect in an ex ovo chick embryo model. Second, doxorubicin-loaded mesoporous silica nanoparticles were introduced into the cells, which would act as vehicles for the drug being released. The effect of the drug was evaluated in a coculture in vitro model with mammary cancer cells. Third, the combination of endostatin transfection and doxorubicin-nanoparticle loading was carried out with the decidua mesenchymal stromal cells. This final cell platform was shown to retain its tumor-migration capacity in vitro, and the combined in vitro therapeutic efficacy was confirmed through a 3D spheroid coculture model using both cancer and endothelial cells. The results presented here show great potential for the development of combination therapies based on genetically-engineered cells that can simultaneously act as cellular vehicles for drug-loaded nanoparticles. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

19 pages, 5888 KiB  
Article
Iontosomes: Electroresponsive Liposomes for Topical Iontophoretic Delivery of Chemotherapeutics to the Buccal Mucosa
by Kiran Sonaje, Vasundhara Tyagi, Yong Chen and Yogeshvar N. Kalia
Pharmaceutics 2021, 13(1), 88; https://doi.org/10.3390/pharmaceutics13010088 - 11 Jan 2021
Cited by 11 | Viewed by 2164
Abstract
The targeted local delivery of anticancer therapeutics offers an alternative to systemic chemotherapy for oral cancers not amenable to surgical excision. However, epithelial barrier function can pose a challenge to their passive topical delivery. The charged, deformable liposomes—“iontosomes”—described here are able to overcome [...] Read more.
The targeted local delivery of anticancer therapeutics offers an alternative to systemic chemotherapy for oral cancers not amenable to surgical excision. However, epithelial barrier function can pose a challenge to their passive topical delivery. The charged, deformable liposomes—“iontosomes”—described here are able to overcome the buccal mucosal barrier via a combination of the electrical potential gradient imposed by iontophoresis and their shape-deforming characteristics. Two chemotherapeutic agents with very different physicochemical properties, cisplatin (CDDP) and docetaxel (DTX), were co-encapsulated in cationic iontosomes comprising 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and Lipoid-S75. The entrapment of CDDP was improved by formulating it in anionic reverse micelles of dipalmitoyl-sn-glycero-3-phospho-rac-glycerol sodium (DPPG) prior to loading in the iontosomes. Cryo-TEM imaging clearly demonstrated the iontosomes’ electroresponsive shape-deformable properties. The in vitro transport study using porcine mucosa indicated that iontosomes did not enter the mucosa without an external driving force. However, anodal iontophoresis resulted in significant amounts of co-encapsulated CDDP and DTX being deposited in the buccal mucosa; e.g., after current application for 10 min, the deposition of CDDP and DTX was 13.54 ± 1.78 and 10.75 ± 1.75 μg/cm2 cf. 0.20 ± 0.07 and 0.19 ± 0.09 μg/cm2 for the passive controls—i.e., 67.7- and 56.6-fold increases—without any noticeable increase in their transmucosal permeation. Confocal microscopy confirmed that the iontosomes penetrated the mucosa through the intercellular spaces and that the penetration depth could be controlled by varying the duration of current application. Overall, the results suggest that the combination of topical iontophoresis with a suitable nanocarrier system can be used to deliver multiple “physicochemically incompatible” chemotherapeutics selectively to oral cancers while decreasing the extent of systemic absorption and the associated risk of side effects. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

17 pages, 2599 KiB  
Article
New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation
by Lucía Margarita Valenzuela-Salas, Alberto Blanco-Salazar, Jesús David Perrusquía-Hernández, Mario Nequiz-Avendaño, Paris A. Mier-Maldonado, Balam Ruiz-Ruiz, Verónica Campos-Gallegos, María Evarista Arellano-García, Juan Carlos García-Ramos, Alexey Pestryakov, Luis Jesús Villarreal-Gómez, Yanis Toledano-Magaña and Nina Bogdanchikova
Pharmaceutics 2021, 13(1), 65; https://doi.org/10.3390/pharmaceutics13010065 - 07 Jan 2021
Cited by 6 | Viewed by 3345
Abstract
Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs’ antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated [...] Read more.
Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs’ antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated AgNPs formulation and their selective antitumor and amoebicidal activity. The protein-coated AgNPs formulation exhibits a half-inhibitory concentration (IC50) = 19.7 µM (2.3 µg/mL) that is almost 10 times more potent than carboplatin (first-line chemotherapeutic agent) to inhibit the proliferation of the highly aggressive human adenocarcinoma HCT-15. The main death pathway elicited by AgNPs on HCT-15 is apoptosis, which is probably stimulated by reactive oxygen species (ROS) overproduction on mitochondria. A concentration of 111 µM (600 µg/mL) of metallic silver contained in AgNPs produces neither cytotoxic nor genotoxic damage on human peripheral blood lymphocytes. Thus, the AgNPs formulation evaluated in this work improves both the antiproliferative potency on HCT-15 cultures and cytotoxic selectivity ten times more than carboplatin. A similar mechanism is suggested for the antiproliferative activity observed on HM1-IMSS trophozoites (IC50 = 69.2 µM; 7.4 µg/mL). There is no change in cell viability on mice primary cultures of brain, liver, spleen, and kidney exposed to an AgNPs concentration range from 5.5 µM to 5.5 mM (0.6 to 600 µg/mL). The lethal dose was determined following the OECD guideline 420 for Acute Oral Toxicity Assay, obtaining an LD50 = 2618 mg of Ag/Kg body weight. All mice survived the observational period; the histopathology and biochemical analysis show no differences compared with the negative control group. In summary, all results from toxicological evaluation suggest a Category 5 (practically nontoxic) of the Globally Harmonized System of Classification and Labelling of Chemicals for that protein-coated AgNPs after oral administration for a short period and urge the completion of its preclinical toxicological profile. These findings open new opportunities in the development of selective, safe, and effective AgNPs formulations for the treatment of cancer and parasitic diseases with a significant reduction of side effects. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

21 pages, 4636 KiB  
Article
A Bilayer Vaginal Tablet for the Localized Delivery of Disulfiram and 5-Fluorouracil to the Cervix
by Ismin Zainol Abidin, Emanuele Rezoagli, Bianca Simonassi-Paiva, Gustavo Waltzer Fehrenbach, Kevin Masterson, Robert Pogue, Zhi Cao, Neil Rowan, Emma J. Murphy and Ian Major
Pharmaceutics 2020, 12(12), 1185; https://doi.org/10.3390/pharmaceutics12121185 - 06 Dec 2020
Cited by 9 | Viewed by 2602
Abstract
This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The [...] Read more.
This study was performed to develop an adjuvant therapy in the form of a self-administered vaginal tablet regimen for the localized delivery of chemotherapeutic drugs. This therapy will help to reduce relapse by eradicating cancerous cells in the margin of cervical tumors. The vaginal tablet is a very common formulation that is easy to manufacture, easy to place in the vagina, and has a low cost of manufacture, making them ideal for use in developing countries. A combination of disulfiram and 5-fluorouracil, which are both off-patent drugs and provide different modes of action, were evaluated. The tablets developed were evaluated for weight variation, thickness, hardness, friability, swelling index, differential scanning calorimetry (DSC), particle morphology, in vitro drug release, and cytotoxicity on Ca-Ski cells. Both layers were designed to release both drugs concurrently for a synergistic effect. The polymer–polymer interaction between the layers was able to reduce the loss of formulation due to chitosan. While the bilayer tablet had satisfactory performance in the physicochemical tests, in vitro cell culture with Ca-Ski also showed a synergistic effect using a combination of drugs at a low dose. However, the formulation only had 24-h dose release before degradation. Further drug combinations should be evaluated in subsequent studies. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

22 pages, 3841 KiB  
Article
pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy
by Silvia Tampucci, Lorenzo Guazzelli, Susi Burgalassi, Sara Carpi, Patrizia Chetoni, Andrea Mezzetta, Paola Nieri, Beatrice Polini, Christian Silvio Pomelli, Eleonora Terreni and Daniela Monti
Pharmaceutics 2020, 12(11), 1078; https://doi.org/10.3390/pharmaceutics12111078 - 11 Nov 2020
Cited by 49 | Viewed by 4216
Abstract
For topical treatment of skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active fatty acid-protic ionic liquids (FA-PILs), [...] Read more.
For topical treatment of skin cancer, the design of pH-responsive nanocarriers able to selectively release the drug in the tumor acidic microenvironment represents a reliable option for targeted delivery. In this context, a series of newly synthesized surface-active fatty acid-protic ionic liquids (FA-PILs), based on tetramethylguanidinium cation and different natural hydrophobic fatty acid carboxylates, have been investigated with the aim of developing a pH-sensitive nanostructured drug delivery system for cutaneous administration in the skin cancer therapy. The capability of FA-PILs to arrange in micelles when combined with each other and with the non-ionic surfactant d-α-Tocopherol polyethylene glycol succinate (vitamin E TPGS) as well as their ability to solubilize imiquimod, an immuno-stimulant drug used for the treatment of skin cancerous lesions, have been demonstrated. The FA-PILs-TPGS mixed micelles showed pH-sensitivity, suggesting that the acidic environment of cancer cells can trigger nanostructures’ swelling and collapse with consequent rapid release of imiquimod and drug cytotoxic potential enhancement. The in vitro permeation/penetration study showed that the micellar formulation produced effective imiquimod concentrations into the skin exposed to acid environment, representing a potential efficacious and selective drug delivery system able to trigger the drug release in the tumor tissues, at lower and less irritating drug concentrations. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

17 pages, 1755 KiB  
Article
The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells
by Usama A. Fahmy, Hibah M. Aldawsari, Shaimaa M. Badr-Eldin, Osama A. A. Ahmed, Nabil A. Alhakamy, Helal H. Alsulimani, Filippo Caraci and Giuseppe Caruso
Pharmaceutics 2020, 12(10), 956; https://doi.org/10.3390/pharmaceutics12100956 - 11 Oct 2020
Cited by 23 | Viewed by 2626
Abstract
Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, [...] Read more.
Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

17 pages, 2037 KiB  
Article
Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
by Fabricio Ledezma-Gallegos, Rafael Jurado, Roser Mir, Luis Alberto Medina, Laura Mondragon-Fuentes and Patricia Garcia-Lopez
Pharmaceutics 2020, 12(9), 897; https://doi.org/10.3390/pharmaceutics12090897 - 22 Sep 2020
Cited by 17 | Viewed by 3109
Abstract
Cervical cancer is usually diagnosed in the later stages despite many campaigns for early detection and continues to be a major public health problem. The standard treatment is cisplatin-based chemotherapy plus radiotherapy, but patient response is far from ideal. In the research for [...] Read more.
Cervical cancer is usually diagnosed in the later stages despite many campaigns for early detection and continues to be a major public health problem. The standard treatment is cisplatin-based chemotherapy plus radiotherapy, but patient response is far from ideal. In the research for new drugs that enhance the activity of cisplatin, different therapeutic agents have been tested, among them the antiprogestin mifepristone. Nevertheless, the efficacy of cisplatin is limited by its low specificity for tumor tissue, which causes severe side effects. Additionally, cervical tumors often become drug resistant. These problems could possibly be addressed by the use of liposome nanoparticles to encapsulate drugs and deliver them to the target. The aim of this study was to prepare liposome nanoparticles that co-encapsulate cisplatin and mifepristone, evaluate their cytotoxicity against HeLa cells and in vivo with subcutaneous inoculations of xenografts in nu/nu mice, and examine some plausible mechanisms of action. The liposomes were elaborated by the reverse-phase method and characterized by physicochemical tests. The nanoparticles had a mean particle size of 109 ± 5.4 nm and a Zeta potential of −38.7 ± 1.2 mV, the latter parameter indicating a stable formulation. These drug-loaded liposomes significantly decreased cell viability in vitro and tumor size in vivo, without generating systemic toxicity in the animals. There was evidence of cell cycle arrest and increased apoptosis. The promising results with the co-encapsulation of cisplatin/mifepristone warrant further research. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

19 pages, 9053 KiB  
Article
Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells
by Soyoung Hwang, Dong Min Shin and Jeong Hee Hong
Pharmaceutics 2020, 12(9), 816; https://doi.org/10.3390/pharmaceutics12090816 - 27 Aug 2020
Cited by 11 | Viewed by 2407
Abstract
IP3 receptor-binding protein released with IP3 (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 [...] Read more.
IP3 receptor-binding protein released with IP3 (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

0 pages, 5656 KiB  
Article
RETRACTED: The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells
by Zuhier A. Awan, Usama A. Fahmy, Shaimaa M. Badr-Eldin, Tarek S. Ibrahim, Hani Z. Asfour, Mohammed W. Al-Rabia, Anas Alfarsi, Nabil A. Alhakamy, Wesam H. Abdulaal, Hadeel Al Sadoun, Nawal Helmi, Ahmad O. Noor, Filippo Caraci, Diena M. Almasri and Giuseppe Caruso
Pharmaceutics 2020, 12(7), 597; https://doi.org/10.3390/pharmaceutics12070597 - 27 Jun 2020
Cited by 28 | Viewed by 3224 | Retraction
Abstract
Statins, including simvastatin (SMV), are commonly used for the control of hyperlipidaemia and have also proven therapeutic and preventative effects in cardiovascular diseases. Besides that, there is an emerging interest in their use as antineoplastic drugs as demonstrated by different studies showing their [...] Read more.
Statins, including simvastatin (SMV), are commonly used for the control of hyperlipidaemia and have also proven therapeutic and preventative effects in cardiovascular diseases. Besides that, there is an emerging interest in their use as antineoplastic drugs as demonstrated by different studies showing their cytotoxic activity against different cancer cells. In this study, SMV-loaded emulsomes (SMV-EMLs) were formulated and evaluated for their cytotoxic activity in MCF-7 breast cancer cells. The emulsomes were prepared using a modified thin-film hydration technique. A Box–Behnken model was used to investigate the impact of formulation conditions on vesicle size and drug entrapment. The optimized formulation showed a spherical shape with a vesicle size of 112.42 ± 2.1 nm and an entrapment efficiency of 94.34 ± 1.11%. Assessment of cytotoxic activities indicated that the optimized SMV-EMLs formula exhibited significantly lower half maximal inhibitory concentration (IC50) against MCF-7 cells. Cell cycle analysis indicated the accumulation of cells in the G2-M phase as well as increased cell fraction in the pre-G1 phase, suggesting an enhancement of anti-apoptotic activity of SMV. The staining of cells with Annex V revealed an increase in early and late apoptosis, in line with the increased cellular content of caspase-3 and Bax. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. In conclusion, SMV-EMLs demonstrated superior cell death-inducing activity against MCF-7 cells compared to pure SMV. This is mediated, at least in part, by enhanced pro-apoptotic activity and MMP modulation of SMV. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Figure 1

19 pages, 3214 KiB  
Article
PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment
by Ana I. Fraguas-Sánchez, Ana I. Torres-Suárez, Marie Cohen, Florence Delie, Daniel Bastida-Ruiz, Lucile Yart, Cristina Martin-Sabroso and Ana Fernández-Carballido
Pharmaceutics 2020, 12(5), 439; https://doi.org/10.3390/pharmaceutics12050439 - 09 May 2020
Cited by 50 | Viewed by 5990
Abstract
The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and [...] Read more.
The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (−16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher—although not statistically significant—tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

Review

Jump to: Research

40 pages, 3971 KiB  
Review
Liposomal-Based Formulations: A Path from Basic Research to Temozolomide Delivery Inside Glioblastoma Tissue
by Roxana-Maria Amarandi, Alina Ibanescu, Eugen Carasevici, Luminita Marin and Brindusa Dragoi
Pharmaceutics 2022, 14(2), 308; https://doi.org/10.3390/pharmaceutics14020308 - 27 Jan 2022
Cited by 16 | Viewed by 3969
Abstract
Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. [...] Read more.
Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

27 pages, 3442 KiB  
Review
Microneedles Drug Delivery Systems for Treatment of Cancer: A Recent Update
by Aravindram Attiguppe Seetharam, Hani Choudhry, Muhammed A. Bakhrebah, Wesam H. Abdulaal, Maram Suresh Gupta, Syed Mohd Danish Rizvi, Qamre Alam, Siddaramaiah, Devegowda Vishakante Gowda and Afrasim Moin
Pharmaceutics 2020, 12(11), 1101; https://doi.org/10.3390/pharmaceutics12111101 - 17 Nov 2020
Cited by 29 | Viewed by 5366
Abstract
Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small [...] Read more.
Microneedles (MNs) are tiny needle like structures used in drug delivery through layers of the skin. They are non-invasive and are associated with significantly less or no pain at the site of administration to the skin. MNs are excellent in delivering both small and large molecules to the subjects in need thereof. There exist several strategies for drug delivery using MNs, wherein each strategy has its pros and cons. Research in this domain lead to product development and commercialization for clinical use. Additionally, several MN-based products are undergoing clinical trials to evaluate its safety, efficacy, and tolerability. The present review begins by providing bird’s-eye view about the general characteristics of MNs followed by providing recent updates in the treatment of cancer using MNs. Particularly, we provide an overview of various aspects namely: anti-cancerous MNs that work based on sensor technology, MNs for treatment of breast cancer, skin carcinoma, prostate cancer, and MNs fabricated by additive manufacturing or 3 dimensional printing for treatment of cancer. Further, the review also provides limitations, safety concerns, and latest updates about the clinical trials on MNs for the treatment of cancer. Furthermore, we also provide a regulatory overview from the “United States Food and Drug Administration” about MNs. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

35 pages, 2606 KiB  
Review
Timeline of Translational Formulation Technologies for Cancer Therapy: Successes, Failures, and Lessons Learned Therefrom
by Alexandre Pérez-López, Cristina Martín-Sabroso, Ana Isabel Torres-Suárez and Juan Aparicio-Blanco
Pharmaceutics 2020, 12(11), 1028; https://doi.org/10.3390/pharmaceutics12111028 - 28 Oct 2020
Cited by 5 | Viewed by 5236
Abstract
Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, [...] Read more.
Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn. The successes (and failures) achieved with formulations that have been approved in Europe and/or by the FDA for the three major types of cancer therapy (peptide-based therapy, chemotherapy, and radiotherapy) are reviewed herein, covering the period from the approval of the first prolonged-release system for hormonal therapy to the appearance of the first biodegradable microspheres intended for chemoembolization in 2020. In addition, those products that have entered phase III clinical trials that have been active over the last five years are summarized in order to outline future research trends and possibilities that lie ahead to develop clinically translatable formulations for cancer treatment. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

16 pages, 1503 KiB  
Review
Mesoporous Silica Nanoparticles as Theranostic Antitumoral Nanomedicines
by Alejandro Baeza and Maria Vallet-Regí
Pharmaceutics 2020, 12(10), 957; https://doi.org/10.3390/pharmaceutics12100957 - 11 Oct 2020
Cited by 29 | Viewed by 2778
Abstract
Nanoparticles have become a powerful tool in oncology not only as carrier of the highly toxic chemotherapeutic drugs but also as imaging contrast agents that provide valuable information about the state of the disease and its progression. The enhanced permeation and retention effect [...] Read more.
Nanoparticles have become a powerful tool in oncology not only as carrier of the highly toxic chemotherapeutic drugs but also as imaging contrast agents that provide valuable information about the state of the disease and its progression. The enhanced permeation and retention effect for loaded nanocarriers in tumors allow substantial improvement of selectivity and safety of anticancer nanomedicines. Additionally, the possibility to design stimuli-responsive nanocarriers able to release their payload in response to specific stimuli provide an excellent control on the administered dosage. The aim of this review is not to present a comprehensive revision of the different theranostic mesoporous silica nanoparticles (MSN) which have been published in the recent years but just to describe a few selected examples to offer a panoramic view to the reader about the suitability and effectiveness of these nanocarriers in the oncology field. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

25 pages, 4871 KiB  
Review
Nanogel: A Versatile Nano-Delivery System for Biomedical Applications
by Yanlong Yin, Ben Hu, Xiao Yuan, Li Cai, Huile Gao and Qian Yang
Pharmaceutics 2020, 12(3), 290; https://doi.org/10.3390/pharmaceutics12030290 - 23 Mar 2020
Cited by 136 | Viewed by 9783
Abstract
Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, [...] Read more.
Nanogel-based nanoplatforms have become a tremendously promising system of drug delivery. Nanogels constructed by chemical crosslinking or physical self-assembly exhibit the ability to encapsulate hydrophilic or hydrophobic therapeutics, including but not limited to small-molecule compounds and proteins, DNA/RNA sequences, and even ultrasmall nanoparticles, within their 3D polymer network. The nanosized nature of the carriers endows them with a specific surface area and inner space, increasing the stability of loaded drugs and prolonging their circulation time. Reactions or the cleavage of chemical bonds in the structure of drug-loaded nanogels have been shown to trigger the controlled or sustained drug release. Through the design of specific chemical structures and different methods of production, nanogels can realize diverse responsiveness (temperature-sensitive, pH-sensitive and redox-sensitive), and enable the stimuli-responsive release of drugs in the microenvironments of various diseases. To improve therapeutic outcomes and increase the precision of therapy, nanogels can be modified by specific ligands to achieve active targeting and enhance the drug accumulation in disease sites. Moreover, the biomembrane-camouflaged nanogels exhibit additional intelligent targeted delivery features. Consequently, the targeted delivery of therapeutic agents, as well as the combinational therapy strategy, result in the improved efficacy of disease treatments, though the introduction of a multifunctional nanogel-based drug delivery system. Full article
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Show Figures

Graphical abstract

Back to TopTop