Highly ordered hexagonal (MCM-41) mesoporous silica nanoparticles (MSNs) loaded with etoposide (ETO) were synthesized and functionalized with amino groups (MCM-41-A). The objective was to investigate effect of functionalization and compare release profile of poorly water soluble drug ETO from MCM-41 and its functionalized variant in simulated and biorelevant dissolution media with the aim of dissolution enhancement of ETO. An extensive drug release study was performed in both fasted and fed state dissolution media. Additionally, release study was performed in presence of enzymes to investigate interaction of amine moiety with gelatin shell and its effect on in vitro drug release. All the samples were thoroughly characterized by powder X-ray diffraction, nitrogen adsorption isotherms, thermogravimetric analysis and electron microscopy to determine their structure, physicochemical properties and percentage loading. An assessment of release profile of crystalline ETO, marketed formulation (MF), ETO-MCM-41 and ETO-MCM-41-A. ETO-MCM-41 nanoparticles showed a higher percentage release with remarkable 5.1 fold increment with respect to plain ETO and 1.16 times as compared to MF. The results showed the release kinetics followed Weibull and Higuchi model for MCM-41 and MCM-41-A nanoparticles respectively. Study revealed that amination modified the release pattern with ETO-MCM-41-A exhibiting a sustained release pattern as compared to ETO-MCM-41.