Gel-Based Drug Delivery Systems for Cancer Treatment

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 17541

Special Issue Editors

Yale School of Medicine, Yale University, New Haven, CT 06520, USA
Interests: nanomedicine; hydrogel; tumor hyperthermia

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Guest Editor
Yale School of Medicine, Yale University, New Haven, CT 06520, USA
Interests: hydrogel; drug release
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Hydrogels have been widely utilized for drug delivery to various diseases, especially for cancer, in which the unique features (e.g., ROS, GSH, hypoxia and acidic pH) are beneficial for the design of drug delivery systems.  Numerous new drug delivery strategies based on functional hydrogels have been proposed in recent years. For example, injectable hydrogels can be implanted into tumor tissue in a minimally invasive manner to maintain a high drug concentration and reduce systemic toxic side effects. A pH-sensitive hydrogel maintains its stable state at physiological pH, but is labile at mildly acidic pH in tumor microenvironments, which can be exploited for enhanced cancer therapy. Hydrogel vaccines show great potential in cancer immunotherapy by causing a potent and durable antitumor response. The development of hydrogels with desirable functionalities has a promising future in intelligent therapy of cancer.

This Special Issue intends to highlight the topics related to the use of functional gels in assisting cancer treatment of therapeutic agents, delivering therapy-related components with different modes of administration. Additionally, gels used for stimuli-responsive drug release and for facilitating chemo-dynamic therapy, immunotherapy and thermotherapy will also be featured.

Scope:

  1. Functional hydrogel

    1.1 Stimuli-responsive hydrogel

          (Endogenous stimulus: pH, GSH, ROS, MMP2, etc.; exogenous stimuli: light, thermo, etc.)

    1.2 Bioinspired hydrogel

  1. Smart delivery hydrogel

    2.1 Injectable hydrogel (minimally invasive administration)

    2.2 Nanogel (systemic administration)

  1. Hydrogel for combination therapy

    3.1 Chemo-dynamic therapy

    3.2 Immunotherapy

    3.3 Thermotherapy

  1. Wound dressing or wound healing

Dr. Haoan Wu
Prof. Dr. Xingchun Gao
Guest Editors

Manuscript Submission Information

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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. Gels 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 2600 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.

Published Papers (9 papers)

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Research

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17 pages, 5047 KiB  
Article
Acanthus mollis Formulations for Transdermal Delivery: From Hydrogels to Emulsions
by Patrícia Matos, Maria Teresa Batista, Francisco Veiga, Artur Figueirinha and Ana Figueiras
Gels 2024, 10(1), 36; https://doi.org/10.3390/gels10010036 - 31 Dec 2023
Viewed by 978
Abstract
Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations—an oil-in-water cream and two hydrogels (Carbopol [...] Read more.
Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations—an oil-in-water cream and two hydrogels (Carbopol 940 and Pluronic F-127)—was determined using Franz diffusion cells. Detection and quantification of the compounds was performed via high-performance liquid chromatography with a photodiode array (HPLC-PDA). DIBOA, a bioactive compound of this medicinal plant, exhibited release kinetics of the Weibull model for the Carbopol and Pluronic F-127 formulation, identifying it as a potential active agent to optimize the topical distribution of the formulations. The implications extend to applications in inflammation treatment and tyrosinase inhibition, suggesting that it can make a significant contribution to addressing skin conditions, including melanoma and various inflammatory diseases. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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17 pages, 4465 KiB  
Article
Formulation of Transliposomal Nanocarrier Gel Containing Strychnine for the Effective Management of Skin Cancer
by Perwez Alam, Mohd Imran, Dipak Kumar Gupta and Ali Akhtar
Gels 2023, 9(10), 831; https://doi.org/10.3390/gels9100831 - 20 Oct 2023
Cited by 1 | Viewed by 941
Abstract
Strychnine (STCN) has demonstrated an exceptional anticancer effect against various cancers. However, the STCN clinical utility has been hampered by its low water solubility, restricted therapeutic window, short half-life, and significant toxicity. The objective of this investigation was to design and optimize a [...] Read more.
Strychnine (STCN) has demonstrated an exceptional anticancer effect against various cancers. However, the STCN clinical utility has been hampered by its low water solubility, restricted therapeutic window, short half-life, and significant toxicity. The objective of this investigation was to design and optimize a formulation of strychnine-loaded transliposomes (STCN–TLs) for dermal administration of STCN to treat skin cancer. The formulations of STCN–TL were examined in terms of vesicle size (VS), polydispersity index (PDI), entrapment efficiency (EE), and in vitro delivery. The improved STCN–TL formulation exhibited VS, PDI, EE, and in vitro delivery of 101.5 ± 2.14 nm, 0.218 ± 0.12, 81.74 ± 1.43%, and 85.39 ± 2.33%, respectively. In an ex vivo penetration, the created STCN–TL formulation demonstrated a 2.5-fold increase in permeability compared to the STCN solution. CLSM pictures of skin (rat) revealed that the rhodamine B-loaded transliposome preparation penetrated deeper than the rhodamine B hydroalcoholic mixture. Additionally, rat skin managed with STCN–TL nanogel exhibited a significant increase in Cskin max and AUC0-8 compared to rat skin treated with traditional STCN gel. The findings demonstrated that the transliposome preparation might be a suitable nanocarrier for the cutaneous distribution of STCN in the amelioration of skin cancer. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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14 pages, 3368 KiB  
Article
Red Light and 5% Aminolaevulinic Acid (5%) Inhibit Proliferation and Migration of Dysplastic Oral Keratinocytes via ROS Production: An In Vitro Study
by Tania Vanessa Pierfelice, Milos Lazarevic, Dijana Mitic, Nadja Nikolic, Milena Radunovic, Giovanna Iezzi, Adriano Piattelli and Jelena Milasin
Gels 2023, 9(8), 604; https://doi.org/10.3390/gels9080604 - 26 Jul 2023
Cited by 2 | Viewed by 929
Abstract
Undiagnosed and untreated oral precancerous lesions often progress into malignancies. Photodynamic therapy (PDT) might be a minimally invasive alternative to conventional treatments. 5-aminolevulinic acid (5-ALA) is one of the most commonly used photosensitizers in PDT, and it is effective on many cancer types. [...] Read more.
Undiagnosed and untreated oral precancerous lesions often progress into malignancies. Photodynamic therapy (PDT) might be a minimally invasive alternative to conventional treatments. 5-aminolevulinic acid (5-ALA) is one of the most commonly used photosensitizers in PDT, and it is effective on many cancer types. However, its hydrophilic characteristic limits cell membrane crossing. In the present study, the effect of a newly formulated gel containing 5% 5-ALA in combination with red light (ALAD-PDT) on a premalignant oral mucosa cell line was investigated. The dysplastic oral keratinocyte (DOK) cells were incubated with ALAD at different concentrations (0.1, 0.5, 1, and 2 mM) at two different times, 45 min or 4 h, and then irradiated for 7 min with a 630 nm LED (25 J/cm2). MTT assay, flow cytometry, wound healing assay, and quantitative PCR (qPCR) were performed. ALAD-PDT exerted inhibitory effects on the proliferation and migration of DOK cells by inducing ROS and necrosis. mRNA analysis showed modulation of apoptosis-related genes’ expression (TP53, Bcl-2, survivin, caspase-3, and caspase-9). Furthermore, there was no difference between the shorter and longer incubation times. In conclusion, the inhibitory effect of the ALAD-PDT protocol observed in this study suggests that ALAD-PDT could be a promising novel treatment for oral precancerous lesions. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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13 pages, 3606 KiB  
Article
Optimization of the Dose Rate Effect in Tetrazolium Gellan Gel Dosimeters
by Kalin I. Penev, Matt Mulligan and Kibret Mequanint
Gels 2023, 9(4), 334; https://doi.org/10.3390/gels9040334 - 14 Apr 2023
Cited by 1 | Viewed by 1007
Abstract
Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability. However, a previously developed commercial product (the ClearView 3D Dosimeter) based on a tetrazolium salt dispersed within a gellan [...] Read more.
Tetrazolium salts provide an appealing candidate for 3D gel dosimeters as they exhibit a low intrinsic color, no signal diffusion and excellent chemical stability. However, a previously developed commercial product (the ClearView 3D Dosimeter) based on a tetrazolium salt dispersed within a gellan gum matrix presented a noticeable dose rate effect. The goal of this study was to find out whether ClearView could be reformulated in order to minimize the dose rate effect by optimizing of the tetrazolium salt and gellan gum concentrations and by the addition a thickening agent, ionic crosslinkers, and radical scavengers. To that goal, a multifactorial design of experiments (DOE) was conducted in small-volume samples (4-mL cuvettes). It showed that the dose rate could be effectively minimized without sacrificing the integrity, chemical stability, or dose sensitivity of the dosimeter. The results from the DOE were used to prepare candidate formulations for larger-scale testing in 1-L samples to allow for fine-tuning the dosimeter formulation and conducting more detailed studies. Finally, an optimized formulation was scaled-up to a clinically relevant volume of 2.7 L and tested against a simulated arc treatment delivery with three spherical targets (diameter 3.0 cm), requiring different doses and dose rates. The results showed excellent geometric and dosimetric registration, with a gamma passing rate (at 10% minimum dose threshold) of 99.3% for dose difference and distance to agreement criteria of 3%/2 mm, compared to 95.7% in the previous formulation. This difference may be of clinical importance, as the new formulation may allow the quality assurance of complex treatment plans, relying on a variety of doses and dose rates; thus, expanding the potential practical application of the dosimeter. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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20 pages, 6163 KiB  
Article
DOE-Assisted Formulation, Optimization, and Characterization of Tioconazole-Loaded Transferosomal Hydrogel for the Effective Treatment of Atopic Dermatitis: In Vitro and In Vivo Evaluation
by Rohini Kharwade, Nemat Ali, Purushottam Gangane, Kapil Pawar, Sachin More, Muzaffar Iqbal, Abid R. Bhat, Abdullah F. AlAsmari and Mohammed Kaleem
Gels 2023, 9(4), 303; https://doi.org/10.3390/gels9040303 - 04 Apr 2023
Cited by 4 | Viewed by 1685
Abstract
The present study was performed to determine the therapeutic effects of tioconazole (Tz)-loaded novel transferosome carriers (TFs) for the treatment of atopic dermatitis (AD). Method: Tioconazole transferosomes suspension (TTFs) was formulated and optimized using a 32 factorial design. After that, the optimized [...] Read more.
The present study was performed to determine the therapeutic effects of tioconazole (Tz)-loaded novel transferosome carriers (TFs) for the treatment of atopic dermatitis (AD). Method: Tioconazole transferosomes suspension (TTFs) was formulated and optimized using a 32 factorial design. After that, the optimized batch of TTFs loaded into Carbopol 934 and sodium CMC was prepared with hydrogel and noted as TTFsH. Subsequently, it was evaluated for pH, spread ability, drug content, in vitro drug release, viscosity, in vivo scratching and erythema score, skin irritation, and histopathology study. Result: The optimized batch of TTFs (B4) showed the values of vesicle size, flux, and entrapment efficiency to be 171.40 ± 9.03 nm, 48.23 ± 0.42, and 93.89 ± 2.41, respectively. All batches of TTFsH showed sustained drug release for up to 24 h. The F2 optimized batch released Tz in an amount of 94.23 ± 0.98% with a flux of 47.23 ± 0.823 and followed the Higuchi kinetic model. The in vivo studies provided evidence that the F2 batch of TTFsH was able to treat atopic dermatitis (AD) by reducing the erythema and the scratching score compared to that of the marketed formulation (Candiderm cream, Glenmark). The histopathology study supported the result of the erythema and scratching score study with intact skin structure. It showed that a formulated low dose of TTFsH was safe and biocompatible to both the dermis and the epidermis layer of skin. Conclusion: Thus, a low dose of F2-TTFsH is a promising tool that effectively targeted the skin for the topical delivery of Tz to treat atopic dermatitis symptoms. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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16 pages, 13274 KiB  
Article
Development and Evaluation of Novel Encapsulated Isoeugenol-Liposomal Gel Carrier System for Methicillin-Resistant Staphylococcus aureus
by Sulaiman Mohammed Alnasser, Faizul Azam, Mohammed H. Alqarni, Alhussain H. Aodah, Sana Hashmi, Mehnaz Kamal, Alotaibi Meshal and Aftab Alam
Gels 2023, 9(3), 228; https://doi.org/10.3390/gels9030228 - 15 Mar 2023
Cited by 1 | Viewed by 1290
Abstract
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) bacteria have seriously threatened the health and safety of the world’s population. This challenge demands the development of alternative therapies based on plant origin. This molecular docking study ascertained the orientation and intermolecular interactions of isoeugenol [...] Read more.
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) bacteria have seriously threatened the health and safety of the world’s population. This challenge demands the development of alternative therapies based on plant origin. This molecular docking study ascertained the orientation and intermolecular interactions of isoeugenol within penicillin-binding protein 2a. In this present work, isoeugenol as an anti-MRSA therapy was selected by encapsulating it into a liposomal carrier system. After encapsulation into the liposomal carrier, it was evaluated for encapsulation efficiency (%), particle size, zeta potential, and morphology. The percentage entrapment efficiency (% EE) was observed to be 57.8 ± 2.89% with a particle size of 143.31 ± 7.165 nm, a zeta potential of (−)25 mV, and morphology was found to be spherical and smooth. After this evaluation, it was incorporated into a 0.5% Carbopol gel for a smooth and uniform distribution on the skin. Notably, the isoeugenol-liposomal gel was smooth on the surface with a pH of 6.4, suitable viscosity, and spreadability. Interestingly, the developed isoeugenol-liposomal gel was safe for human use, with more than 80% cell viability. The in vitro drug release study shows promising results with 75.95 ± 3.79% of drug release after 24 h. The minimum inhibitory concentration (MIC) was 8.236 µg/mL. Based on this, it can be concluded that encapsulating isoeugenol into the liposomal gel is a potential carrier for MRSA treatment. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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Review

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19 pages, 2332 KiB  
Review
Injectable Thermoresponsive Hydrogels for Cancer Therapy: Challenges and Prospects
by Sandrine Tanga, Marique Aucamp and Poornima Ramburrun
Gels 2023, 9(5), 418; https://doi.org/10.3390/gels9050418 - 16 May 2023
Cited by 5 | Viewed by 2587
Abstract
The enervating side effects of chemotherapeutic drugs have necessitated the use of targeted drug delivery in cancer therapy. To that end, thermoresponsive hydrogels have been employed to improve the accumulation and maintenance of drug release at the tumour site. Despite their efficiency, very [...] Read more.
The enervating side effects of chemotherapeutic drugs have necessitated the use of targeted drug delivery in cancer therapy. To that end, thermoresponsive hydrogels have been employed to improve the accumulation and maintenance of drug release at the tumour site. Despite their efficiency, very few thermoresponsive hydrogel-based drugs have undergone clinical trials, and even fewer have received FDA approval for cancer treatment. This review discusses the challenges of designing thermoresponsive hydrogels for cancer treatment and offers suggestions for these challenges as available in the literature. Furthermore, the argument for drug accumulation is challenged by the revelation of structural and functional barriers in tumours that may not support targeted drug release from hydrogels. Other highlights involve the demanding preparation process of thermoresponsive hydrogels, which often involves poor drug loading and difficulties in controlling the lower critical solution temperature and gelation kinetics. Additionally, the shortcomings in the administration process of thermosensitive hydrogels are examined, and special insight into the injectable thermosensitive hydrogels that reached clinical trials for cancer treatment is provided. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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36 pages, 5919 KiB  
Review
Gel Formulations for Topical Treatment of Skin Cancer: A Review
by Marta Slavkova, Borislav Tzankov, Teodora Popova and Christina Voycheva
Gels 2023, 9(5), 352; https://doi.org/10.3390/gels9050352 - 22 Apr 2023
Cited by 8 | Viewed by 5309
Abstract
Skin cancer, with all its variations, is the most common type of cancer worldwide. Chemotherapy by topical application is an attractive strategy because of the ease of application and non-invasiveness. At the same time, the delivery of antineoplastic agents through the skin is [...] Read more.
Skin cancer, with all its variations, is the most common type of cancer worldwide. Chemotherapy by topical application is an attractive strategy because of the ease of application and non-invasiveness. At the same time, the delivery of antineoplastic agents through the skin is difficult because of their challenging physicochemical properties (solubility, ionization, molecular weight, melting point) and the barrier function of the stratum corneum. Various approaches have been applied in order to improve drug penetration, retention, and efficacy. This systematic review aims at identifying the most commonly used techniques for topical drug delivery by means of gel-based topical formulations in skin cancer treatment. The excipients used, the preparation approaches, and the methods characterizing gels are discussed in brief. The safety aspects are also highlighted. The combinatorial formulation of nanocarrier-loaded gels is also reviewed from the perspective of improving drug delivery characteristics. Some limitations and drawbacks in the identified strategies are also outlined and considered within the future scope of topical chemotherapy. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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22 pages, 7753 KiB  
Review
The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review
by Shebin Tharakan, Iman Raja, Annette Pietraru, Elina Sarecha, Andrei Gresita, Eugen Petcu, Azhar Ilyas and Michael Hadjiargyrou
Gels 2023, 9(4), 274; https://doi.org/10.3390/gels9040274 - 25 Mar 2023
Cited by 2 | Viewed by 1861
Abstract
Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has [...] Read more.
Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has shown promising results both in vitro and in vivo to eradicate tumor cells while promoting bone regeneration. The loading of hydrogels with chemotherapeutic drugs provides a route for site-specific targeted therapy for osteosarcoma. Current studies demonstrate tumor regression in vivo and lysis of tumor cells in vitro when exposed to doped hydrogel scaffolds. Additionally, novel stimuli-responsive hydrogels are able to react with the tissue microenvironment to facilitate the controlled release of anti-tumor drugs and with biomechanical properties that can be modulated. This narrative review of the current literature discusses both in vitro and in vivo studies of different hydrogels, including stimuli-responsive, designed to treat bone osteosarcoma. Future applications to address patient treatment for this bone cancer are also discussed. Full article
(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Title: Docosahexaenoic acid improves the antineoplastic effect of a hyaluronic acid and folic acid-based hydrogel containing cisplatin in human ovarian cancer cells in vitro

Author: Dr. Roberta Cassano

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