Physical insights into salicylic acid release from poly(anhydrides)

Abstract

Salicylic acid (SA) based biodegradable polyanhydrides (PAHs) are of great interest for drug delivery in a variety of diseases and disorders owing to the multi-utility of SA. There is a need for the design of SA-based PAHs for tunable drug release, optimized for the treatment of different diseases. In this study, we devised a simple strategy for tuning the release properties and erosion kinetics of a family of PAHs. PAHs incorporating SA were derived from related aliphatic diacids, varying only in the chain length, and prepared by simple melt condensation polymerization. Upon hydrolysis induced erosion, the polymer degrades into cytocompatible products, including the incorporated bioactive SA and diacid. The degradation follows first order kinetics with the rate constant varying by nearly 25 times between the PAH obtained with adipic acid and that with dodecanedioic acid. The release profiles have been tailored from 100% to 50% SA release in 7 days across the different PAHs. The release rate constants of these semi-crystalline, surface eroding PAHs decreased almost linearly with an increase in the diacid chain length, and varied by nearly 40 times between adipic acid and dodecanedioic acid PAH. The degradation products with SA concentration in the range of 30-350 ppm were used to assess cytocompatibility and showed no cytotoxicity to HeLa cells. This particular strategy is expected to (a) enable synthesis of application specific PAHs with tunable erosion and release profiles; (b) encompass a large number of drugs that may be incorporated into the PAH matrix. Such a strategy can potentially be extended to the controlled release of other drugs that may be incorporated into the PAH backbone and has important implications for the rational design of drug eluting bioactive polymers.

Polyanhydride Chemistry

“…Poly­(anhydride-ester) based polyactives can also be employed as prodrug platforms for the controlled release of various therapeutics and bioactive small organic molecules including antioxidants, − anti-inflammatory drugs, , antiseptics, , antibiotics, and antimicrobial drugs . Recently, Madras et al also reported several poly­(anhydride-esters) that contained bioactive molecules such as salicylic acid and aspirin in the polymer main chain. − They studied the release kinetics associated with the hydrolytic degradation of the polymer matrix and subsequently investigated their anti-inflammatory and antibacterial activities.…”

“… 186 Recently, Madras et al also reported several poly(anhydride-esters) that contained bioactive molecules such as salicylic acid and aspirin in the polymer main chain. 187 − 190 They studied the release kinetics associated with the hydrolytic degradation of the polymer matrix and subsequently investigated their anti-inflammatory and antibacterial activities.…”