Smart polymersome carriers for osteoporosis treatment: Enhanced bone regeneration via targeted teriparatide delivery

Targeted drug delivery improves therapeutic efficacy while minimizing off-target effects. In this study, PLGA-PEG-Su-Asp (PPSA) copolymers were synthesized to develop teriparatide-loaded nano-polymersomes (PPSA-PTH1-34 NP) for bone-targeted delivery. Nanoparticles were prepared by nanoprecipitation and optimized using a central composite design. The optimized nanoparticles had a size of 245.78 ± 8.2 nm, PDI of 0.352 ± 0.12, ZP of -18.89 ± 0.1 mV, and 72.20 ± 2.9 % drug entrapment efficiency. PPSA-PTH 1-34 exhibited strong affinity (64.86 %) to hydroxyapatite, enhancing targeting efficiency. In vitro assays in MG-63 cells confirmed time- and concentration-dependent proliferation, uptake efficiency, increased ALP activity, and mineralization. In vivo studies using an (ovariectomizd) OVX rat model showed that PPSA-PTH 1-34 significantly improved bone regeneration compared to free PTH1-34. These findings demonstrate that PPSA-based NP provide a promising platform for targeted and sustained PTH 1-34 delivery, potentially improving therapeutic outcomes in osteoporosis treatment.