دورية أكاديمية
Nasal administration of a temozolomide-loaded thermoresponsive nanoemulsion reduces tumor growth in a preclinical glioblastoma model.
العنوان: | Nasal administration of a temozolomide-loaded thermoresponsive nanoemulsion reduces tumor growth in a preclinical glioblastoma model. |
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المؤلفون: | Michels LR; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90.610-000, Porto Alegre, RS, Brazil., Fachel FNS; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90.610-000, Porto Alegre, RS, Brazil., Schuh RS; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90.610-000, Porto Alegre, RS, Brazil; Laboratório Células, Tecidos e Genes, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, R. Ramiro Barcelos, 2350, 90.035-007, Porto Alegre, RS, Brazil., Azambuja JH; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), R. Sarmento Leite, 245, 90.050-170, Porto Alegre, RS, Brazil., de Souza PO; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), R. Sarmento Leite, 245, 90.050-170, Porto Alegre, RS, Brazil., Gelsleichter NE; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), R. Sarmento Leite, 245, 90.050-170, Porto Alegre, RS, Brazil., Lenz GS; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), R. Sarmento Leite, 245, 90.050-170, Porto Alegre, RS, Brazil., Visioli F; Programa de Pós-Graduação em Odontologia, UFRGS, R. Ramiro Barcelos, 2492, 90.035-002, Porto Alegre, RS, Brazil., Braganhol E; Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), R. Sarmento Leite, 245, 90.050-170, Porto Alegre, RS, Brazil., Teixeira HF; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 90.610-000, Porto Alegre, RS, Brazil. Electronic address: helder.teixeira@ufrgs.br. |
المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Mar; Vol. 355, pp. 343-357. Date of Electronic Publication: 2023 Feb 09. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
مواضيع طبية MeSH: | Glioblastoma*/drug therapy , Glioblastoma*/pathology , Brain Neoplasms*/drug therapy , Brain Neoplasms*/pathology, Rats ; Animals ; Swine ; Temozolomide/therapeutic use ; Administration, Intranasal ; Poloxamer/therapeutic use ; Cell Line, Tumor ; Antineoplastic Agents, Alkylating/therapeutic use |
مستخلص: | Glioblastoma (GB) is the worst and most common primary brain tumor. Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, at least 50% of TMZ treated patients do not respond to TMZ and the development of chemoresistance is a major problem. Here, we designed a lipid nanoemulsion containing a thermoresponsive polymer (poloxamer 407) aiming to improve TMZ release into the brain via nasal delivery. Increasing amounts of poloxamer 407 were added to preformed nanoemulsions (250 nm-range) obtained by spontaneous emulsification. The influence of the polymer concentration (from 2.5% to 12.5%) and temperature on viscosity was clearly evidenced. Such effect was also noticed on the mucoadhesiveness of formulations, as well as TMZ release rate and retention/permeation through nasal porcine mucosa using Franz-type diffusion cells. From these results, a formulation containing 10% of poloxamer (NTMZ-P10) was selected for further experiments by nasal route. A significantly higher TMZ amount was observed in the brain of rats from NTMZ-P10 in comparison with controls. Finally, our results show that formulation reduced significantly tumor growth by three-fold: 103.88 ± 43.67 mm 3 (for NTMZ-P10) and 303.28 ± 95.27 mm 3 (control). Overall, these results suggest the potential of the thermoresponsive formulation, administered by the non-invasive nasal route, as a future effective glioblastoma treatment. Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
فهرسة مساهمة: | Keywords: Glioblastoma; Nanoemulsions; Nasal route; Poloxamer 407; Temozolomide |
المشرفين على المادة: | YF1K15M17Y (Temozolomide) 106392-12-5 (Poloxamer) 0 (Antineoplastic Agents, Alkylating) |
تواريخ الأحداث: | Date Created: 20230202 Date Completed: 20230313 Latest Revision: 20230331 |
رمز التحديث: | 20240628 |
DOI: | 10.1016/j.jconrel.2023.01.070 |
PMID: | 36731799 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1873-4995 |
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DOI: | 10.1016/j.jconrel.2023.01.070 |