Bio-derived solvents for in situ forming implants.

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Green Chemistry

Background:

• In situ forming implants (ISFIs) are advanced injectable drug delivery systems.
• N-Methyl-2-pyrrolidone (NMP) is a common ISFI solvent but poses toxicity risks.
• Safer, bio-derived solvents are needed for ISFI development.

Purpose of the Study:

• To evaluate dimethyl isosorbide (DMI) and γ-valerolactone (GVL) as NMP alternatives in ISFIs.
• To assess the impact of these solvents on ISFI properties and drug release.
• To compare the performance of DMI- and GVL-based ISFIs with NMP-based systems.

Main Methods:

• Formulated poly(lactic-co-glycolic acid) (PLGA) ISFIs using NMP, DMI, or GVL with eosin Y or testosterone.
• Characterized ISFIs for rheology, injectability, morphology, and in vitro/in vivo drug release.
• Developed a two-stage model to analyze release kinetics and diffusion coefficients.

Main Results:

• GVL exhibited NMP-like rheology, while DMI showed higher viscosity.
• NMP and DMI ISFIs formed spherical implants; GVL ISFIs collapsed.
• GVL ISFIs reduced burst release but had faster overall release kinetics.
• In vivo testosterone release was comparable across all solvent formulations.

Conclusions:

• DMI and GVL are viable, safer alternatives to NMP for ISFI development.
• Solvent choice significantly influences ISFI morphology and drug release profiles.
• These bio-derived solvents offer comparable in vivo performance to NMP.