In situ subcutaneously injectable thermosensitive PEG-PLGA diblock and PLGA-PEG-PLGA triblock copolymer composite as sustained delivery of bispecific anti-CD3 scFv T-cell/anti-EGFR Fab Engager (BiTEE)

Wei, Pu Sheng; Chen, Yi Jou; Lin, Shyr Yi; Chuang, Kai‐Hsiang; Sheu, Ming Thau; Ho, Hsiu O.

doi:10.1016/j.biomaterials.2021.121166

Cited by 23 publications

(6 citation statements)

References 41 publications

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“…However, further increase in temperature lead to serious dehydration of the PEG shell and dramatical shrinkage of the micelles, contributing to the precipitation of the copolymer. 28 , 29 The thermosensitive properties of PLGA-PEG-PLGA copolymers can be modulated by the structure of the copolymer. The hydrophobicity of the PLGA-PEG-PLGA molecules increased by increasing of the LA/GA ratio and PLGA block length, leading to a higher sol-to-gel phase transition temperature 30 .…”

Section: Resultsmentioning

confidence: 99%

“…The sol-gel transition temperature of thermosensitive hydrogel suitable for clinical application should be around 25 ◦ C, for the easy handling of injectables at room temperature and in situ gel formation after injection with a minimal extent of shrinkage to avoid initial rapid release of the drugs. 28 Furthermore, drugs incorporated PLGA-PEG-PLGA copolymers do have an effect on the transition temperature. DOX incorporated hydrogels exhibited a higher transition temperature, while CDDP incorporated hydrogels had a lower temperature than the copolymer itself.…”

Section: Resultsmentioning

confidence: 99%

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In situ Co-Delivery of Doxorubicin and Cisplatin by Injectable Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment

Si¹,

Xia²,

Cong³

et al. 2022

IJN

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Purpose Osteosarcoma is considered as the most common primary malignant bone tumor in children and adolescents, and the treatments including chemotherapy and surgery were far from satisfactory. Localized tumor treatments by hydrogels incorporating combined chemotherapeutic drugs have recently emerged as superior approaches for enhanced anti-tumor effects and reduced systemic toxicity. Methods A novel injectable thermosensitive poly (lactide-co- glycolide)-poly (ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer hydrogel containing doxorubicin and cisplatin for the localized chemotherapy of osteosarcoma were synthesized and characterized. The in vitro drug release properties of the drugs-loaded hydrogels were investigated. To study the anti-tumor efficacy of hydrogels depots in vitro, the cytotoxicity and apoptosis rate against Saos-2 and MG-63 cells were evaluated by MTT, Annexin V and PCR methods. The in vivo synergistic anti-tumor efficacy of the multi-drugs co-loaded hydrogels was investigated by human osteosarcoma xenografts. Additionally, the systemic toxic side effects were evaluated by ex vivo histological analysis of the major organs of the mice. Results The PLGA-PEG-PLGA copolymer solution underwent a sol-gel transition at appropriate temperature and degraded in the PBS, presenting a friendly biocompatibility in vitro. The in vitro cell viability tests demonstrated that DOX and CDDP co-loaded hydrogels exhibited synergistic anti-proliferation effect, due to the sustained release of drugs from the drugs-loaded hydrogel. The treatment with DOX and CDDP co-loaded hydrogel led to the highest efficiency in inhibiting the tumor growth, enhanced tumor necrosis rate and increased regulation of the apoptosis-related gene expressions, indicating a synergistic anti-tumor efficacy in vivo. Additionally, ex vivo histological analysis of the nude mice exhibited low systemic toxicity. Conclusion The combination treatment of osteosarcoma by localized, sustained co-delivery of DOX and CDDP by PLGA-PEG-PLGA hydrogel may serve as a promising strategy for efficient clinical treatment of osteosarcoma.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In situ Co-Delivery of Doxorubicin and Cisplatin by Injectable Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment

Si¹,

Xia²,

Cong³

et al. 2022

IJN

View full text Add to dashboard Cite

show abstract

“…Wei et al [87] subcutaneously injected thermosensitive hydrogels (DT gels) based on PLGA-PEG-PLGA, which were loaded with a bispecific anticluster of CD3 scFv T-cell/antiepidermal growth factor receptor (EGFR) Fab engager (BiTEE). The temperaturesensitive property of the 28-34 • C sol-gel transition was suitable for injection.…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy

et al. 2022

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Thermosensitive hydrogels, having unique sol–gel transition properties, have recently received special research attention. These hydrogels exhibit a phase transition near body temperature. This feature is the key to their applications in human medicine. In addition, hydrogels can quickly gel at the application site with simple temperature stimulation and without additional organic solvents, cross-linking agents, or external equipment, and the loaded drugs can be retained locally to improve the local drug concentration and avoid unexpected toxicity or side effects caused by systemic administration. All of these features have led to thermosensitive hydrogels being some of the most promising and practical drug delivery systems. In this paper, we review thermosensitive hydrogel materials with biomedical application potential, including natural and synthetic materials. We describe their structural characteristics and gelation mechanism and briefly summarize the mechanism of drug release from thermosensitive hydrogels. Our focus in this review was to summarize the application of thermosensitive hydrogels in disease treatment, including the postoperative recurrence of tumors, the delivery of vaccines, the prevention of postoperative adhesions, the treatment of nervous system diseases via nasal brain targeting, wound healing, and osteoarthritis treatment.

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“…Organic materials, such as the Food and Drug Administration (FDA)-approved polymers used in therapeutics, polyethylene glycol (PEG), and poly lactic-co-glycolic acid (PLGA), have been widely explored and applied in delivery systems, tissue engineering, etc. [ 1 , 2 ]. Inorganic materials have gotten increasing attention due to their controllable synthesis and rigid structures.…”

Section: Introductionmentioning

confidence: 99%

Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy

Han

Alu

et al. 2022

Bioactive Materials

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In situ subcutaneously injectable thermosensitive PEG-PLGA diblock and PLGA-PEG-PLGA triblock copolymer composite as sustained delivery of bispecific anti-CD3 scFv T-cell/anti-EGFR Fab Engager (BiTEE)

Cited by 23 publications

References 41 publications

In situ Co-Delivery of Doxorubicin and Cisplatin by Injectable Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment

In situ Co-Delivery of Doxorubicin and Cisplatin by Injectable Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment

Thermosensitive Hydrogels and Advances in Their Application in Disease Therapy

Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy

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