Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle: in vitro and in vivo evaluation

Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40 mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400 mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications.