Effect of pH on salicylic acid-based poly(anhydride-ester): Implications for polymer degradation and controlled salicylic acid release

Abstract

Salicylic acid (SA)-based poly(anhydride-esters) (SAPAEs) hydrolytically degrade to release SA in a controlled manner over extended time periods. While these polymers have been well investigated under in vivo conditions, this study is the first detailed, systematic assessment of in vitro polymer degradation over a range of pH values. To investigate the effect of pH conditions on SAPAE degradation, in vitro degradation studies were conducted on SAPAE disks over a wide pH range (2.0, 4.0, 6.0, 7.4, 8.0, 9.0, and 10.0) for 30 days. Several parameters were evaluated, including SA concentrations in the degradation media, polymer mass loss, water uptake in the polymer matrices, and SA solubility at different pH values to substantiate SA release results and characterize the in vitro polymer degradation process. Complete SA release was achieved at more basic conditions (pH 9.0 and 10.0) over 9 days, whereas less than 41% SA was released over the same time period at neutral pH conditions (pH 8.0 and 7.4). By comparison, SA release was minimal in acidic pH conditions. Overall, we present quantitative data of polymer degradation as defined by SA in vitro release, which increased with increasing pH values. More basic conditions promoted polymer degradation, whereas acidic conditions minimized polymer degradation.

4D Printable Salicylic Acid Photopolymers for Sustained Drug Releasing, Shape Memory, Soft Tissue Scaffolds

“…As expected, variation of the NaOH concentration could be used to vary mass loss in all species, which indicates that the degradation mechanism is purely hydrolytic (Figure , SI Figure 24). Most importantly, by these degradation studies we confirmed the release of salicylic acid derivatives in all cases through spectroscopy, with more prolonged release demonstrated by our materials compared with other PolyAspirins and encapsulated/incorporated forms of salicylic acid. ,,− ,, The degradation also follows a surface erosion process, as confirmed through optical observations of film erosion (SI Figure 25) as well as of porous structures over time as well as through more complex drug release studies. Through selection of the linker species, the daily released concentration could be varied while maintaining linear release profiles over time.…”

“…Several studies have used salicylic acid as building blocks for either soft thermoset materials displaying low strains at failure of approximately 20% during uniaxial tensile testing or functional polymers with temporal components in their design (4D polymers). ,− Notably, the Uhrich group has contributed a large body of work developing PolyAspirin, attempting to leverage polymer design to overcome the aforementioned drug delivery loading limitations where salicylic acid is directly incorporated into the polymer backbone to serve as a therapeutic agent upon release. ,,,, While the release profiles of this work are promising with regard to sustained release greater than 24 h and ∼45% loading of the salicylic acid (the highest to date), a significant limitation with this technique is the difficulties with processing these materials into geometries which may be of clinical use and extending the release times past ∼60 days. ,,, Recently, this work has focused on making the materials more processable, including developing extrudable formulations, which unfortunately required lowered the salicylic acid concentration in the polymer backbone to achieve greater flow . Other attempts at incorporating salicylic acid have focused on leveraging salicylic acid in the polymer backbone.…”

“…39,42,46,50,51 While the release profiles of this work are promising with regard to sustained release greater than 24 h and ∼45% loading of the salicylic acid (the highest to date), a significant limitation with this technique is the difficulties with processing these materials into geometries which may be of clinical use and extending the release times past ∼60 days. 42,50,52,53 Recently, this work has focused on making the materials more processable, including developing extrudable formulations, which unfortunately required lowered the salicylic acid concentration in the polymer backbone to achieve greater flow. 54 Other attempts at incorporating salicylic acid have focused on leveraging salicylic acid in the polymer backbone.…”