Tunable drug release profiles from salicylate-based poly(anhydride-ester) matrices using small molecule admixtures

Abstract

Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory drug, chemically incorporated into the polymer backbone provide high inherent drug loading. These poly(anhydride-esters) hydrolytically degrade to release salicylic acid over extended time periods (>30 days); however, an initial lag period of no salicylic acid release is observed. This lag period could be unfavorable in applications where immediate salicylic acid release is desired. Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were admixed with various small molecules as a means to shorten or eliminate the lag period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures resulted in immediate salicylic acid release and a decrease in glass transition temperatures compared to polymer alone. By varying the amounts of salicylic acid and salicylic acid prodrugs incorporated into the polymer matrix, immediate and constant salicylic acid release profiles over varied time periods were achieved.

Salicylic acid (SA)‐eluting bone regeneration scaffolds with interconnected porosity and local and sustained SA release

“…At predetermined time points, 0.5 mL release media was removed and 0.5 mL fresh PBS was added to maintain sink conditions. The removed media were analyzed by a Perkin Elmer Lambda XLS spectrophotometer (Waltham, MA) at λ = 303 nm, the maximum absorption wavelength for SA at which all other SAP degradation products minimally absorb . SA concentrations were calculated based on a calibration curve of absorbance from solutions prepared with known SA concentrations.…”

Sustained, localized salicylic acid delivery enhances diabetic bone regeneration via prolonged mitigation of inflammation

“…At predetermined time points, agar systems were cut open along the midline and rinsed with 15 mL of PBS; this SA quantity should represent the local SA concentration at the bone defect. Media containing the recovered SA was then analyzed by an Perkin Elmer Lambda XLS spectrophotometer (Waltham, MA) at λ = 303 nm, the maximum absorption wavelength for SA at which all other SAPAE degradation products minimally absorb . SA concentrations were calculated based on a calibration curve of absorbance from solutions prepared with known SA concentrations.…”

“…Media containing the recovered SA was then analyzed by an Perkin Elmer Lambda XLS spectrophotometer (Waltham, MA) at k 5 303 nm, the maximum absorption wavelength for SA at which all other SAPAE degradation products minimally absorb. 15 SA concentrations were calculated based on a calibration curve of absorbance from solutions prepared with known SA concentrations. Before the cut-open time, 50 mL of the surrounding release media was removed every other day and replenished with 50 mL fresh PBS to ensure sink conditions.…”

“…This offers an exceedingly high SA loading (∼70%) compared to < 30% loadings from physical incorporation . The SAPAE degradation mechanism is primarily surface erosion and yields a near zero‐order release profile, meaning that the SA release rate is relatively constant and delivery is predictable . The duration of SA release from SAPAE can last from weeks to months, making it an ideal material to target chronic conditions, such as diabetic bone healing .…”

“…15 The duration of SA release from SAPAE can last from weeks to months, making it an ideal material to target chronic conditions, such as diabetic bone healing. 15 SA is a well-known nonsteroidal antiinflammatory drug that suppresses the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-jB). 16 NF-jB is involved in the production of proinflammatory cytokines, such as tumor necrosis factor (TNF)-a, interleukin (IL)21 and IL-6, which can increase bone resorption and reduce bone formation, especially in diabetic subjects.…”