Design and development of pH-sensitive nanocarriers using molecularly imprinted polymers for the targeted delivery of sodium thiopental†

Sodium thiopental (STL) is an ultrashort-acting barbiturate that acts quickly on the brain, reduces levels of adrenaline, noradrenaline, and dopamine, and has neuroprotective properties. However, its side effects, especially in high doses, can be severe, including respiratory failure and cardiac complications. Molecularly imprinted polymers (MIPs) are three-dimensional polymeric networks that mimic the structure and functionality of target molecules. MIPs include benefits such as stability, selectivity, and cost-effectiveness. Combination with magnetic nanoparticles (MNPs) not only enhances their stability and biocompatibility but also provides magnetic separation capabilities. This research introduces the design and synthesis of pH-sensitive MIPs as targeted nanocarriers for the selective uptake and controlled release of STL molecules. The MIPs were synthesized in various forms, including magnetic core MIPs (MMIPs), standard MIPs (MIPs), and fiber-shaped MIPs (MIP_F), to explore their comparative efficiency and structural advantages. Bemegride (BMG), an antidote structurally similar to STL, was utilized to evaluate the selectivity of these MIP systems. The formation of specific binding sites of STL on MIPs during the polymerization process leads to selective recognition and matches STL's shape, size, and functional groups. In this regard, all types of MIPs exhibited significant rebinding affinities over their non-imprinted polymer (NIP); specifically, MMIPs displayed a high affinity for uptake of STL (393.8 ± 1.328%) against BMG (360.72 ± 6.72%) over 24 h. The pH sensitivity of the nanocarriers was investigated in simulated gastric fluid (SGF) and simulated intestinal fluids (SIF) environments. The quantitative results indicated that the prepared nanocarriers showed a controlled release in SIF environments. MMIPs achieved a release efficiency for STL and BMG of approximately 57.7 ± 0.6% and 85.4 ± 4.6%, respectively, over a 78-hour period. These findings highlight the potential of MMIPs for dual-uptake and targeted release applications of STL in specific pH environments.