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Gel-Based Drug Delivery Systems for Cancer Treatment

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

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 27966

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Special Issue Editors

Dr. Haoan Wu

E-Mail Website1 Website2
Guest Editor

1. Yale School of Medicine, Yale University, New Haven, CT 06520, USA
2. School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
Interests: nanomedicine; hydrogel; tumor hyperthermia
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Xingchun Gao

E-Mail Website
Guest Editor

1. Yale School of Medicine, Yale University, New Haven, CT 06520, USA
2. Institute of Basic Medicine Science, Xi'an Medical University, Xi'an 710021, China
Interests: brain tumor; cell death; immunotherapy; drug resistance; stem cells; nanomaterials
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:

Functional hydrogel

1.1 Stimuli-responsive hydrogel

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

1.2 Bioinspired hydrogel

Smart delivery hydrogel

2.1 Injectable hydrogel (minimally invasive administration)

2.2 Nanogel (systemic administration)

Hydrogel for combination therapy

3.1 Chemo-dynamic therapy

3.2 Immunotherapy

3.3 Thermotherapy

Wound dressing or wound healing

Dr. Haoan Wu
Prof. Dr. Xingchun Gao
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. Gels is an international peer-reviewed open access monthly journal published by MDPI.

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Related Special Issue

Gel-Based Drug Delivery Systems for Cancer Treatment (2nd Edition) in Gels

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

3 pages, 559 KiB

Open AccessEditorial

Editorial for Special Issue: Gel-Based Drug Delivery Systems for Cancer Treatment

by Haoan Wu and Xingchun Gao

Gels 2024, 10(11), 680; https://doi.org/10.3390/gels10110680 - 23 Oct 2024

Viewed by 564

Abstract

In recent years, hydrogel-based cancer drug delivery systems have developed rapidly due to the versatility of hydrogels [...] Full article

(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)

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Research

Jump to: Editorial, Review

13 pages, 4370 KiB

Open AccessArticle

Microparticles Made with Silk Proteins for Melanoma Adjuvant Therapy

by Sonia Trombino, Roberta Sole, Federica Curcio, Rocco Malivindi, Daniele Caracciolo, Silvia Mellace, Dino Montagner and Roberta Cassano

Gels 2024, 10(8), 485; https://doi.org/10.3390/gels10080485 - 23 Jul 2024

Cited by 1 | Viewed by 868

Abstract

Melanoma is one of the most aggressive forms of skin cancer, which is characterized by metastasis and poor prognosis due to the limited effectiveness of current therapies and the toxicity of conventional drugs. For this reason and in recent years, one of the most promising strategies in the treatment of this form of cancer is the use of drug delivery systems as carriers capable of conveying the therapeutic agent into the tumor microenvironment, thus preventing its degradation and improving its safety and effectiveness profiles. In the present work, microparticles based on silk fibroin and epifibroin 0039, silk-derived proteins loaded with idebenone, were created, which act as therapeutic carriers for topical use in the treatment of melanoma. The resulting particles have a spherical shape, good loading efficiency, and release capacity of idebenone. Efficacy studies have demonstrated a reduction in the proliferation of COLO-38, melanoma tumor cells, while safety tests have demonstrated that the microparticles are not cytotoxic and do not possess prosensitizing activity. Notably, transdermal release studies revealed that all particles released idebenone over more days. The analysis of the stimulatory markers of the proinflammatory process, CD54 and CD86, did not show any increase in expression, thus confirming the absence of potential prosesensitization effects of the silk fibroin-based particles. The research, therefore, found that idebenone-loaded silk protein microparticles could effectively reduce the proliferation of melanoma cells without cytotoxicity. This indicates the promise of a safe and effective treatment of melanoma. Full article

(This article belongs to the Special Issue Gel-Based Drug Delivery Systems for Cancer Treatment)

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17 pages, 5047 KiB

Open AccessArticle

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

Cited by 1 | Viewed by 1640

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 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

Open AccessArticle

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 5 | Viewed by 1553

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 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 C_{skin max} and AUC_0-8 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

Open AccessArticle

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 4 | Viewed by 1398

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. 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

Open AccessArticle

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 3 | Viewed by 1468

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 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

Open AccessArticle

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 - 4 Apr 2023

Cited by 9 | Viewed by 2479

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 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

Open AccessArticle

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 3 | Viewed by 1785

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 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

Open AccessReview

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 15 | Viewed by 3994

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 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

Open AccessReview

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 23 | Viewed by 8376

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 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

Open AccessReview

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 3 | Viewed by 2503

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 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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