title: Silica Ouzo Effect: Amphiphilic Drugs Facilitate Nanoprecipitation of Polycondensed Mercaptosilanes.
abstract: Amphiphilic drugs are therapeutic agents whose molecular structures contain both hydrophobic and hydrophilic portions. Here we report a systematic study on how amphiphilic drugs can assist in silica nanoprecipitation. 3-Mercaptopropyltrimethoxysilane (MPTMS) was used as the sole silica material and 12 amphiphilic drugs spanning a wide spectrum of therapeutic categories were included. MPTMS polycondensation was conducted in a DMSO-based organic phase. After a sufficient time, particle formation was induced by injecting a small amount of the organic phase into a water solution containing various amphiphiles. The results show that all amphiphilic drugs studied exerted concentration-dependent facilitating effect on nanoparticle formation. Under certain preparation conditions, the particle solution showed physical stability over a long period and the formed particles could be as small as 100 nm. By systematically varying drug concentrations and injection volumes, the ability of each amphiphile to promote nanoprecipitation can be quantified and compared, based on two novel indices: the area under the critical volume-concentration curve (AUC) and the critical stabilization concentration (CSC). We demonstrate that both ability indices significantly correlated with the drug's log P and critical micelle concentrations (CMC). Furthermore, we have optimized the aging and particle purification condition and extensively characterized our system through comprehensive TEM and zeta-potential measurements, as well as determinations for drug entrapment and release. In conclusion, we have established a quantitative structure-activity relationship for amphiphilic small-molecular drugs in their ability to interact with poly(mercaptopropyl)silsesquioxane species and form nanoparticles via solvent shifting. We speculate that both hydrophobic and electrostatic interactions play important roles in the formation and stabilization of nanoparticles.
authors.affiliation: College of Pharmacy, Taipei Medical University , Taipei 11031, Taiwan, ROC.
authors.forename: Shih-Jiuan
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: College of Pharmacy, Taipei Medical University , Taipei 11031, Taiwan, ROC.|School of Pharmacy, National Defense Medical Center , Taipei 11490, Taiwan, ROC.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: School of Pharmacy, National Defense Medical Center , Taipei 11490, Taiwan, ROC.
authors.forename: Hung-Chang
authors.initials: HC
authors.lastname: Chou
authors.affiliation: School of Pharmacy, National Defense Medical Center , Taipei 11490, Taiwan, ROC.
authors.forename: Teh-Min
authors.initials: TM
authors.lastname: Hu
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D017646:Organosilicon Compounds; D012821:Silanes / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D017646:Organosilicon Compounds; D012821:Silanes; D012822:Silicon Dioxide; C102833:(3-mercaptopropyl)trimethoxysilane