Figari Giorgia, Gonçalves José L M, Diogo Hermínio P, Dionísio Madalena, Farinha José Paulo, Viciosa María Teresa
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, University of Lisbon, Avenida Rovisco Pais, 1049-001 Lisbon, Portugal.
LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal.
Pharmaceutics. 2023 May 30;15(6):1624. doi: 10.3390/pharmaceutics15061624.
To investigate the impact of the surface functionalization of mesoporous silica nanoparticle (MSN) carriers in the physical state, molecular mobility and the release of Fenofibrate (FNB) MSNs with ordered cylindrical pores were prepared. The surface of the MSNs was modified with either (3-aminopropyl) triethoxysilane (APTES) or trimethoxy(phenyl)silane (TMPS), and the density of the grafted functional groups was quantified via H-NMR. The incorporation in the ~3 nm pores of the MSNs promoted FNB amorphization, as evidenced via FTIR, DSC and dielectric analysis, showing no tendency to undergo recrystallization in opposition to the neat drug. Moreover, the onset of the glass transition was slightly shifted to lower temperatures when the drug was loaded in unmodified MSNs, and MSNs modified with APTES composite, while it increased in the case of TMPS-modified MSNs. Dielectric studies have confirmed these changes and allowed researchers to disclose the broad glass transition in multiple relaxations associated with different FNB populations. Moreover, DRS showed relaxation processes in dehydrated composites associated with surface-anchored FNB molecules whose mobility showed a correlation with the observed drug release profiles.
为了研究介孔二氧化硅纳米颗粒(MSN)载体的表面功能化在物理状态、分子流动性以及非诺贝特(FNB)释放方面的影响,制备了具有有序圆柱形孔的MSN。用(3-氨丙基)三乙氧基硅烷(APTES)或三甲氧基(苯基)硅烷(TMPS)对MSN的表面进行修饰,并通过H-NMR对接枝官能团的密度进行定量。MSN约3nm孔中药物的掺入促进了FNB的非晶化,这通过FTIR、DSC和介电分析得到证实,表明与纯药物相反,其没有发生重结晶的趋势。此外,当药物负载在未修饰的MSN和用APTES复合材料修饰的MSN中时,玻璃化转变的起始温度略微向低温偏移,而在用TMPS修饰的MSN的情况下则升高。介电研究证实了这些变化,并使研究人员能够揭示与不同FNB群体相关的多个弛豫过程中的宽玻璃化转变。此外,DRS显示脱水复合材料中与表面锚定的FNB分子相关的弛豫过程,其流动性与观察到的药物释放曲线相关。