Polymer Nanogels as Reservoirs To Inhibit Hydrophobic Drug Crystallization

Abstract

The effects of cross-link density and composition on the loading and in vitro dissolution of the drug phenytoin as amorphous solid dispersions in emulsion polymerized poly(N-isopropylacrylamide) (PNIPAm) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) nanogels were investigated near the lower critical solution temperature (LCST). Nanogel size and particle density in phosphate buffered saline were quantified by dynamic light scattering (DLS) and viscometry experiments, while drug−nanogel interactions were revealed by cross peaks in aqueous-state nuclear Overhauser effect spectroscopy measurements. Spray-dried dispersions (SDDs) of drugloaded PNIPAm nanogel particles (R ≈ 43 nm) were directly visualized by cryogenic transmission electron microscopy and further quantified by small-angle X-ray scattering during in vitro dissolution. SDD dissolution profiles were highly dependent on the nanogel cross-link density and directly correlated with the state of dispersion of the drug-loaded nanogel particles. A balance between net particle hydrophobicity and hydrophilicity along with the distance in temperature from the LCST are shown to dictate the in vitro dissolution of the amorphous solid dispersions. Solubility enhancement mechanisms disclosed in this study provide essential guidance for the design of effective nanogels for oral drug delivery applications.

Role of Polymer Excipients in the Kinetic Stabilization of Drug-Rich Nanoparticles

“…ASDs can promote drug supersaturation by stabilizing the amorphous form of the drug, which has a higher chemical potential compared to its crystalline counterpart. − Polymer excipients are included in the dispersion to prolong the supersaturated state by hindering drug crystallization. The efficacy of ASDs is largely determined by the polymer excipient, and depend on factors such as its hydrophobicity, , molar mass, and intermolecular interactions with the drug …”

Near‐infrared chemiluminescent carbon nanogels for oncology imaging and therapy

“…2,3 On the other hand, combined with the comprehensive properties of hydrogels and nanomaterials, nanogels have aroused widespread concern in the nanomedical fields such as bioimaging and cancer therapy owing to their response to these physiologically related stimuli such as pH, temperature, ionic force, and redox environment. [4][5][6][7][8] Through electrostatic interactions, reverse miniemulsion, desolvation/coacervation, hydrophobic interaction, or cross-linking of monomers, nanogels can be easily entrusted with new applicability for imaging, guided therapy, triggered drug release, or hyperthermia by incorporating the monomers with other nanomaterials. 1,2,9,10 Among the spatiotemporal resolution bioimaging models, such as photoluminescence (PL), computed tomography (CT), and photoacoustic (PA) imaging, chemiluminescence (CL) imaging has been exploited as an ultrasensitive method for quantification and localization of chemical analytes in the living body due to their unnecessary autofluorescence interference.…”

“…On the one hand, smart nanogels with multifunction and novel properties can respond to diverse medically relevant stimuli like pH, temperature, ionic force, and redox environment, and so forth by changing their volume, refractive index, and hydrophilicity−hydrophobicity 2,3 . On the other hand, combined with the comprehensive properties of hydrogels and nanomaterials, nanogels have aroused widespread concern in the nanomedical fields such as bioimaging and cancer therapy owing to their response to these physiologically related stimuli such as pH, temperature, ionic force, and redox environment 4–8 . Through electrostatic interactions, reverse miniemulsion, desolvation/coacervation, hydrophobic interaction, or cross‐linking of monomers, nanogels can be easily entrusted with new applicability for imaging, guided therapy, triggered drug release, or hyperthermia by incorporating the monomers with other nanomaterials 1,2,9,10 .…”

Effect of heterogeneous and homogeneous polymerisation on the structure of pNIPAm nanogels

“…19 In the former approach the starting monomers are dissolved in the feed solution, but the resulting polymer is in the form of a dispersion in an immiscible liquid, 20 often referred to as dis-persion or precipitation polymerisation, 21,22 or emulsion polymerisation if surfactant is used. 23 In homogeneous polymerisation, both monomers and the resulting polymer are dissolved in the media, or swollen in the case of cross-linked gels. 21 In the case of homogeneous polymerisation, the synthesis is performed either in aprotic solvents, such as DMSO 24 or in water (at room temperature).…”