Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules

Abstract

Long-term (multiple-week or -month) release of small, water-soluble molecules from hydrogels remains a significant pharmaceutical challenge, which is typically overcome at the expense of more-complicated drug carrier designs. Such approaches are payload-specific and include covalent conjugation of drugs to base materials or incorporation of micro- and nanoparticles. As a simpler alternative, here we report a mild and simple method for achieving multiple-month release of small molecules from gel-like polymer networks. Densely cross-linked matrices were prepared through ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), all of which are commonly available commercial molecules. The loading of model small molecules (Fast Green FCF and Rhodamine B dyes) within these polymer networks increases with the payload/network binding strength and with the PAH and payload concentrations used during encapsulation. Once loaded into the PAH/PPi and PAH/TPP ionic networks, only a few percent of the payload is released over multiple months. This extended release is achieved regardless of the payload/network binding strength and likely reflects the small hydrodynamic mesh size within the gel-like matrices. Furthermore, the PAH/TPP networks show promising in vitro cytocompatibility with model cells (human dermal fibroblasts), though slight cytotoxic effects were exhibited by the PAH/PPi networks. Taken together, the above findings suggest that PAH/PPi and (especially) PAH/TPP networks might be attractive materials for the multiple-month delivery of drugs and other active molecules (e.g., fragrances or disinfectants).

Fluorinated Methacrylamide Chitosan Hydrogels Enhance Cellular Wound Healing Processes

“…This results in an absorbance shift that is proportional to the metabolic rate. 16 Fluorescence values were determined in the well-plate at an excitation wavelength of 560 nm and emission of 590 nm using a spectrophotometer (Infinite M200, Tecan, Grödig, Austria). Sample values were compared against a dithiothreitol (DTT) standard curve to obtain the absolute values of cell viability in terms of equivalent DTT concentration, which is a direct measure of chemical reduction potenital.…”

“…Sample values were compared against a dithiothreitol (DTT) standard curve to obtain the absolute values of cell viability in terms of equivalent DTT concentration, which is a direct measure of chemical reduction potenital. 16 …”

“…Following the PrestoBlue assay, the wells containing cells had media replaced with 1 ml of 25 mg/ml lysozyme dissolved in PBS and digested at pH 5 for 24 h at 60°C with through mixing by pipetting once every 3 to 4 h. 16 The resulting solutions were transferred to 2 ml tubes and stored at 4 °C for up to 1 wk for the assays below.…”

“…Next, 150 μl of the resulting samples were added to a black 96 well-plate in triplicate followed by 150 μl of Quant-it PicoGreen reagent and incubated for 10 min at room temperature in the dark. 16 Next, fluorescence values (excitation 480 nm, emission 520 nm) were determined using a spectrophotometer (Tecan Infinite M200). Measured fluorescence values were compared against a standard curve created using supplied λDNA standards to find the total dsDNA concentration in each well.…”

Poly(allylamine)/tripolyphosphate coacervates enable high loading and multiple-month release of weakly amphiphilic anionic drugs: an in vitro study with ibuprofen

“…[4][5][6][7][8] These mixtures form coacervates, which have been explored for a variety of applications, ranging from serving as templates for inorganic material synthesis, 8,9 to underwater adhesion, 6,7 to medical imaging, 10 photothermal therapy 11 and controlled release. 5,12,13 When weaker-binding multivalent anions (such as citrate, phosphate and EDTA) are used, the resulting polymer networks contain short-lived ionic crosslinks and have liquid-like properties. 4,6 Consequently, since these coacervates ow and (when prepared as macroscopic phases) fail to hold their shape, 12 they are typically used as colloidal coacervate droplets, which are coated with a stabilizing material that prevents their coalescence.…”