Molecular dynamics investigation of temozolomide encapsulation and controlled release from PLGA carriers

Controlled drug delivery remains a key challenge in the treatment of brain cancer. In this study, the encapsulation and release behavior of the anticancer drug temozolomide (TMZ) in poly(lactic-co-glycolic acid) (PLGA) carriers are investigated using molecular dynamics simulations. Key structural and energetic parameters, including mixing energy, hydrogen bonding, and TMZ mobility, are analyzed at loading levels ranging from 10 to 40 wt% of TMZ. The results revealed that increasing TMZ concentration enhanced PLGA-TMZ interactions and resulted in a more compact carrier structures. A loading ratio of 30 wt% of TMZ was identified as providing the optimal balance between stability and release, characterized by favorable hydrogen bonding and mixing energy. The overall drug release rate from the optimal carrier was determined to be 0.0005 ng/s. Furthermore, water infiltration into the polymer matrix, measured at 0.00011 ng/s, was found to cause swelling and create diffusion pathways, which was identified as the dominant release mechanism.