RESUMO

Ligand-modified nanocarriers can promote oral or inhalative administration of macromolecular drugs across the intestinal or pulmonary mucosa. However, enhancing the unidirectional transport of the nanocarriers through "apical uptake→intracellular transport→basolateral exocytosis" route remains a hot topic and challenge in current research. Forskolin is a naturally occurring diterpenoid compound extracted from the roots of C. forskohlii. In our studies, we found that forskolin could increase the transcellular transport of butyrate-modified nanoparticles by 1.67-fold and 1.20-fold in Caco-2 intestinal epithelial cell models and Calu-3 lung epithelial cell models, respectively. Further mechanistic studies revealed that forskolin, on the one hand, promoted the cellular uptake of butyrate-modified nanoparticles by upregulating the expression of monocarboxylic acid transporter-1 (MCT-1) on the apical membrane. On the other hand, forskolin facilitated the binding of MCT-1 to caveolae, thereby mediating butyrate-modified nanoparticles hijacking caveolae to promote the basolateral exocytosis of butyrate-modified nanoparticles. Studies in normal mice model showed that forskolin could promote the transmucosal absorption of butyrate-modified nanoparticles by >2-fold, regardless of oral or inhalative administration. Using semaglutide as the model drug, both oral and inhalation delivery approaches demonstrated significant hypoglycemic effects in type 2 diabetes mice model, in which inhalative administration was more effective than oral administration. This study optimized the strategies aimed at enhancing the transmucosal absorption of ligand-modified nanocarriers in the intestinal or pulmonary mucosa.

Assuntos

Colforsina , Nanopartículas , Animais , Humanos , Colforsina/administração & dosagem , Administração Oral , Nanopartículas/administração & dosagem , Pulmão/metabolismo , Butiratos/administração & dosagem , Butiratos/farmacocinética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Células CACO-2 , Masculino , Simportadores/metabolismo , Camundongos , Administração por Inalação , Sistemas de Liberação de Medicamentos

RESUMO

PURPOSES: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. METHODS: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. RESULTS: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. CONCLUSIONS: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.

Assuntos

Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Prótese Vascular , Stents , Hemorragias Intracranianas , Resultado do Tratamento

RESUMO

Abstract Purposes: Braided and laser-cut stents both are efficacious and safe for coiling intracranial aneurysms. The study aimed to compare outcomes following braided stent-assisted coil embolization versus laser engraved stent-assisted coil embolization in 266 patients who were diagnosed with unruptured intracranial aneurysms of different types and locations. Methods: Patients with unruptured complex intracranial aneurysms underwent braided (BSE cohort, n = 125) or laser engraved (LSE cohort, n = 141) stent-assisted embolization. Results: The deployment success rate was higher for patients of the LSE cohort than those of the BSE cohort (140 [99%] vs. 117 [94%], p = 0.0142). Seventy-one (fifty-seven percentages) and 73 (52%) were coil embolization procedure success rates of the BSE and the LSE cohorts. Periprocedural intracranial hemorrhage was higher in patients of the BSE cohort than those of the LSE cohort (8 [6%] vs. 1 [1%], p = 0.0142). Four (three percentages) patients from the LSE cohort and 3 (2%) patients from the BSE cohort had in-stent thrombosis during embolization. Permanent morbidities were higher in patients of the LSE cohort than those of the BSE cohort (8 [6%] vs. 1 [1%], p = 0.0389). Higher successful procedures (76% vs. 68%) and fewer postprocedural intracranial hemorrhage (0% vs. 5%) and mortality (0% vs. 5%) were reported for patients of the BSE cohort in posterior circulation aneurysmal location than those of the LSE cohort. Laser engraved stent has fewer problems with deployment and may have better periprocedural and follow-up outcomes after embolization. Conclusions: Braided stent-assisted embolization should be preferred when the aneurysm is present in the posterior circulation.