Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs

Leßmann, Torben; Jones, Seth; Voigt, Tobias; Weisbrod, Samuel H.; Kracker, Oliver; Winter, Steffen; Zúñiga, Luis A.; Stark, Sebastian; Bisek, Nicola; Sprogoe, Kennett

doi:10.1016/j.xphs.2023.05.018

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…When drugs are encapsulated within hydrogels, they not only avert the rapid degradation of chemotherapy drugs in the body but also shield the brain from drug-related toxicity [100][101][102]. (2) Biodegradability: Ideally, the interaction between the host tissue and the hydrogel should orchestrate and fine-tune the degradation process, leading to its eventual disappearance [103].…”

Section: Advantages Of Hydrogels In the Treatment Of Brain Tumorsmentioning

confidence: 99%

Advances in Hydrogels of Drug Delivery Systems for Local Treatment of Brain Tumors

Yang,

Wang,

et al. 2024

Preprint

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The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at a histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach in addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

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Section: Advantages Of Hydrogels In the Treatment Of Brain Tumorsmentioning

confidence: 99%

Advances in Hydrogels of Drug Delivery Systems for Local Treatment of Brain Tumors

Yang,

Wang,

et al. 2024

Preprint

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“…(3) Intelligent drug release control. Smart hydrogels are particularly effective for targeting tumors due to their capacity to respond to various external stimuli and precisely regulate drug release [ 137 , 138 , 139 ]. (4) Accessibility.…”

Section: Advantages Of Hydrogels In the Treatment Of Brain Tumorsmentioning

confidence: 99%

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors

Yang,

Wang,

et al. 2024

Gels

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The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood–brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.

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“…In another example, an imidazoquinoline-based agonist conjugated to cholesterol resulted in localized innate immune activation and reduction in systemic inflammation . Recently, Lessmann et al described a degradable hydrogel as a prodrug for sustained and localized delivery of resiquimod . Fox et al formulated a lipid-based nanosuspension of a synthetic TLR7/8 ligand that facilitated adsorption of the ligand to alum via the structural properties of the helper lipid resulting in enhanced antibody responses .…”

Section: Introductionmentioning

confidence: 99%

“…25 Recently, Lessmann et al described a degradable hydrogel as a prodrug for sustained and localized delivery of resiquimod. 26 Fox et al formulated a lipid-based nanosuspension of a synthetic TLR7/8 ligand that facilitated adsorption of the ligand to alum via the structural properties of the helper lipid resulting in enhanced antibody responses. 27 Modification of the TLR7 molecule benzonaphthyridine (BZN) with a phosphonate group to allow its adsorption onto aluminum hydroxide was another approach 28,29 wherein the phosphonate group on BZN enhanced its aqueous solubility and avoided generation of a physical mixture of two insoluble particulates.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity

Kumar,

Sihag,

Patil

et al. 2024

ACS Pharmacol. Transl. Sci.

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TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure−function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC 50 = 0.85 μM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity and adjuvant potential alone or in combination with alum. Most of the phenolic derivatives were more active than BBIQ and, except for 12b, all were TLR7 specific. Although the synthesized compounds were less active than resiquimod, the immunization data on combination with alum, specifically the IgG1, IgG2b and IgG2c responses, were superior in comparison to BBIQ as well as the reference standard resiquimod. Compound 12b was 5-fold more potent (EC 50 = 0.15 μM in TLR7) than BBIQ and induced double the IgG response to SARS-CoV-2 and hepatitis antigens. Similarly, compound 12c (EC 50 = 0.31 μM in TLR7) was about 3-fold more potent than BBIQ and doubled the IgG levels. Even though compound 12d exhibited low TLR7 activity (EC 50 = 5.13 μM in TLR7), it demonstrated superior adjuvant results, which may be attributed to its enhanced alum adsorption capability as compared with BBIQ and resiquimod. Alum-adsorbed polyphenolic TLR7 agonists thereby represent promising combination adjuvants resulting in a balanced Th1/Th2 immune response.

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Degradable Hydrogel for Sustained Localized Delivery of Anti-Tumor Drugs

Cited by 5 publications

References 39 publications

Advances in Hydrogels of Drug Delivery Systems for Local Treatment of Brain Tumors

Advances in Hydrogels of Drug Delivery Systems for Local Treatment of Brain Tumors

Advances in Hydrogels of Drug Delivery Systems for the Local Treatment of Brain Tumors

Design and Synthesis of Polyphenolic Imidazo[4,5-c]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity

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