• ε-Decalactone copolymerisation yields polyesters with tuneable properties. • Increased ε-decalactone supresses crystallinity of ε-caprolactone copolymers. • Enzymatic degradability of copolymers is maximised at 20–40 mol% ε-decalactone. • ε-Decalactone copolymers form in situ forming implants with improved injectability. • Drug release kinetics from implants can be tuned with ε-decalactone content. Injectable formulations, particularly in situ forming implants (ISFIs), rely on biodegradable polymers to achieve sustained therapeutic delivery. While poly(lactic- co -glycolic acid) (PLGA) is widely used due to its tuneable degradation and biocompatibility, its high viscosity, cost, and batch-to-batch variability limit widespread applicability. Poly(ε-caprolactone) (PCL), a semi-crystalline petroleum-derived polymer, presents as a more cost-effective alternative; however, the very slow degradation rate (2–4 years) and limited solubility in organic solvents used in ISFI formulations restrict its applicability. Therefore, we investigated the copolymerisation of PCL with ε-decalactone, a bio-derived secondary lactone obtained predominately from castor oil, via microbial transformation. Poly(ε-caprolactone)– co -(ε-decalactone) (PCLDL) copolymers were synthesised with varying monomer ratios as alternative ISFI matrices to modulate crystallinity, glass transition temperature, hydrophobicity, and enzymatic degradability of PCL. Increasing the DL mol% led to a transition from solid to semi-solid to liquid polymers at ambient temperature, reflected by a decrease and eventual loss of crystallinity. This change enabled higher polymer loading in ISFI formulations while maintaining adequate injectability. Enzymatic degradability peaked with DL content at 20–40 mol%. Formulated with N -methyl pyrrolidone (NMP), the copolymers were evaluated for ISFI performance using testosterone as a model drug. PCLDL-based ISFI offered significantly lower viscosity and higher injectability compared to PLGA-based ISFIs. Additionally, PCLDL-based ISFI formulations achieved sustained release of testosterone over ∼ 50 d, with release rates modulated by the DL mol%. Overall, this study demonstrates that PCLDL copolymers offer a versatile, tuneable, and biodegradable alternative to conventional PLGA-based ISFIs.
Bazeed et al. (Wed,) studied this question.