All‐Aqueous, Surfactant‐Free, and pH‐Driven Nanoformulation Methods of Dual‐Responsive Polymer Nanoparticles and their Potential use as Nanocarriers of pH‐Sensitive Drugs

• Published in: Macromolecular bioscience 2023-01, Vol.23 (1), p.e2200262-n/a
• Main Authors: Lechuga‐Islas, Víctor D., Trejo‐Maldonado, Melisa, Anufriev, Ilya, Nischang, Ivo, Terzioğlu, İpek, Ulbrich, Jens, Guerrero‐Santos, Ramiro, Elizalde‐Herrera, Luis E., Schubert, Ulrich S., Guerrero‐Sánchez, Carlos
• Format: Article
• Language: English
• Subjects: Bioavailability; Biocompatibility; Buffers; Controlled release; Copolymers; Delayed-Action Preparations - chemistry; Dipyridamole; drug nanocarrier; Hydrogen-Ion Concentration; Light scattering; Nanoparticles; Nanoparticles - chemistry; pH effects; Photon correlation spectroscopy; pH‐driven automated nanoformulation; Polymers; Polymers - chemistry; Polymethyl Methacrylate; Polymethylmethacrylate; Solvents; stimuli‐responsive polymers; Surface-Active Agents; Surfactants
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202200262

All‐aqueous, surfactant‐free, and pH‐driven nanoformulation methods to generate pH‐ and temperature‐responsive polymer nanoparticles (NPs) are described. Copolymers comprising a poly(methyl methacrylate) (PMMA) backbone with a few units of 2‐(dimethylamino)ethyl methacrylate (DMAEMA) are solubilized in acidic buffer (pH 2.0) to produce pH‐sensitive NPs. Copolymers of different molar mass (2.3–11.5 kg mol−1) and DMAEMA composition (7.3–14.2 mol%) are evaluated using a “conventional” pH‐driven nanoformulation method (i.e., adding an aqueous polymer solution (acidic buffer) into an aqueous non‐solvent (basic buffer)) and a robotized method for pH adjustment of polymer dispersions. Dynamic light scattering, zeta‐potential (ζ), and sedimentation‐diffusion analyses suggest the formation of dual‐responsive NPs of tunable size (from 20 to 110 nm) being stable for at least 28 days in the pH and temperature intervals from 2.0 to 6.0 and 25 to 50 °C, respectively. Ultraviolet‐visible spectroscopic experiments show that these NPs can act as nanocarriers for the pH‐sensitive dipyridamole drug, expanding its bioavailability and potential controlled release as a function of pH and temperature. These approaches offer alternative strategies to prepare stimuli‐responsive NPs, avoiding the use of harmful solvents and complex purification steps, and improving the availability of biocompatible polymer nanoformulations for specific controlled release of pH‐sensitive cargos. All‐aqueous, surfactant‐free, and pH‐driven nanoformulation methods to generate pH‐ and temperature‐responsive hydrophopic polymer nanoparticles are described. These nanoformulation methods avoid the use of harmful solvents and complex purification steps, and have the potential to improve the bioavailability of drugs with a pH‐dependent solubility as well as their controlled release as a function of pH and temperature.