New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model
Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellu...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222012987 |
| _version_ | 1811308641704214528 |
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| author | Ana Salas Patricia García-García Patricia Díaz-Rodríguez Carmen Évora Teresa A. Almeida Araceli Delgado |
| author_facet | Ana Salas Patricia García-García Patricia Díaz-Rodríguez Carmen Évora Teresa A. Almeida Araceli Delgado |
| author_sort | Ana Salas |
| collection | DOAJ |
| description | Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50–55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Interestingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas. |
| first_indexed | 2024-04-13T09:26:55Z |
| format | Article |
| id | doaj.art-9db1bca74c1940a0a69cb3b583d661a0 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-13T09:26:55Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-9db1bca74c1940a0a69cb3b583d661a02022-12-22T02:52:24ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113909New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ modelAna Salas0Patricia García-García1Patricia Díaz-Rodríguez2Carmen Évora3Teresa A. Almeida4Araceli Delgado5Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, 38206 La Laguna, Spain; Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, 38206 La Laguna, SpainDepartment of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206 La Laguna, Spain; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38206 La Laguna, SpainInstitute of Biomedical Technologies (ITB), Universidad de La Laguna, 38206 La Laguna, Spain; Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma Group (GI-1645), Facultad de Farmacia, Instituto de Materiales (iMATUS) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, EspañaDepartment of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206 La Laguna, Spain; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38206 La Laguna, SpainDepartment of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, 38206 La Laguna, Spain; Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, 38206 La Laguna, Spain; Corresponding author at: Department of Biochemistry, Microbiology, Cell Biology and Genetics. Universidad de La Laguna, 38206 La Laguna, Spain.Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, 38206 La Laguna, Spain; Institute of Biomedical Technologies (ITB), Universidad de La Laguna, 38206 La Laguna, Spain; Corresponding author at: Department of Chemical Engineering and Pharmaceutical Tecnology, Universidad de La Laguna, 38206 La Laguna, Spain.Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50–55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Interestingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas.http://www.sciencedirect.com/science/article/pii/S0753332222012987Gonadotropin-releasing hormone (GnRH) antagonistsLeiomyomaGanirelixPLGA-microspheresLocal deliveryPreclinical model |
| spellingShingle | Ana Salas Patricia García-García Patricia Díaz-Rodríguez Carmen Évora Teresa A. Almeida Araceli Delgado New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model Biomedicine & Pharmacotherapy Gonadotropin-releasing hormone (GnRH) antagonists Leiomyoma Ganirelix PLGA-microspheres Local delivery Preclinical model |
| title | New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model |
| title_full | New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model |
| title_fullStr | New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model |
| title_full_unstemmed | New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model |
| title_short | New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model |
| title_sort | new local ganirelix sustained release therapy for uterine leiomyoma evaluation in a preclinical organ model |
| topic | Gonadotropin-releasing hormone (GnRH) antagonists Leiomyoma Ganirelix PLGA-microspheres Local delivery Preclinical model |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222012987 |
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