Heat-Triggered Liposomes Could Enable Pulsatile Teriparatide Delivery for Osteoporosis

Hydrophobic ion pairing achieved >75% teriparatide entrapment in sub-200 nm monodispersed liposomes, outperforming other entrapment methods. Transition temperatures of 38-50°C were obtained by modulating phospholipid composition. In vitro assays demonstrated temperature-dependent release kinetics. Released teriparatide maintained biological activity at the PTH1 receptor.

In vitro formulation study. Hydrophobic ion pairing was used to create a hydrophobic teriparatide complex for liposomal entrapment. Liposomes prepared with various phospholipid compositions to achieve different phase transition temperatures. Characterized by size, dispersity, and entrapment efficiency. Release kinetics tested at different temperatures. Biological activity confirmed using a PTH1 receptor cell-based assay.

Patient adherence to daily teriparatide injections is poor, limiting the clinical benefit of the only approved bone-building osteoporosis therapy. A delivery system that releases teriparatide in controlled bursts could transform treatment into a longer-acting, more convenient therapy.

This proof-of-concept addresses two major challenges in peptide drug delivery: efficiently loading water-soluble peptides into lipid carriers, and controlling their release with an external trigger (heat). If developed further, this approach could be applied to many other therapeutic peptides requiring pulsatile delivery.

In vitro proof-of-concept only — no animal or human testing. The practical method of applying heat to trigger release in vivo is not addressed. External heating may be difficult to implement for bone-targeting applications. Long-term stability of the formulation not assessed. Scaling up hydrophobic ion pairing for manufacturing not demonstrated.