In vitro drug release from self-catalyzed poly(ortho ester): case study of 5-fluorouracil

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Drug Delivery

Background:

• Poly(ortho esters) are advanced polymers with tunable properties.
• Incorporating lactic or glycolic acid segments modifies polymer degradation.
• These polymers show promise for controlled release of therapeutic agents.

Purpose of the Study:

• To investigate the in vitro drug release characteristics of novel self-catalyzed poly(ortho esters).
• To evaluate the influence of polymer composition on drug release kinetics.
• To assess the potential of these polymers for delivering antifibroblastic agents.

Main Methods:

• Synthesis of poly(ortho esters) by reacting diols with a diketene acetal, incorporating lactic or glycolic acid dimer segments.
• In vitro drug release studies using 5-fluorouracil as a model drug.
• Analysis of drug release mechanisms (erosion vs. diffusion) based on polymer composition.

Main Results:

• Polymer erosion rate is controllable by adjusting the concentration of diol-lactate segments.
• A 90/10 or 80/20 diol/diol-lactate ratio resulted in 5-fluorouracil release primarily via erosion.
• Lower diol-lactate content led to combined diffusion and erosion release mechanisms.
• Drug release rate is influenced by the diol's alkyl chain length but not by drug loading.

Conclusions:

• Self-catalyzed poly(ortho esters) with tailored lactic/glycolic acid content offer controlled drug release profiles.
• These polymers are suitable for applications requiring sustained release of antifibroblastic agents, such as post-glaucoma surgery.
• Polymer backbone structure significantly impacts drug release kinetics, independent of drug loading.