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

Area of Science:

• Polymer chemistry
• Drug delivery systems
• Materials science

Background:

• Poly(anhydride-esters) allow high loading of salicylic acid, a nonsteroidal anti-inflammatory drug.
• These polymers exhibit hydrolytic degradation, releasing salicylic acid over >30 days but with an initial release lag.

Purpose of the Study:

• To investigate methods for shortening or eliminating the initial salicylic acid release lag period from poly(anhydride-esters).
• To achieve immediate and controlled salicylic acid release profiles.

Main Methods:

• Poly(anhydride-esters) with varying lag periods (2 and 11 days) were admixed with salicylic acid and/or salicylic acid prodrugs at 1%, 5%, and 10% (w/w).
• Physical admixtures were analyzed for salicylic acid release profiles and changes in glass transition temperatures.

Main Results:

• All admixtures demonstrated immediate salicylic acid release, eliminating the initial lag period.
• A decrease in glass transition temperatures was observed in all admixed formulations compared to the neat polymer.
• Varying the amounts of incorporated salicylic acid and prodrugs allowed for tunable, immediate, and constant release over extended periods.

Conclusions:

• Physical admixture of poly(anhydride-esters) with salicylic acid or its prodrugs effectively overcomes the initial release lag.
• This strategy provides a versatile approach to engineer immediate and sustained drug release profiles for enhanced therapeutic efficacy.