Citation: Runrui Liao, Huiling Zeng, Jiahui Zou, Wei He, Hairong Wang. Natural products self-assembling permeation enhancer for intestinal delivery of calcitonin[J]. Chinese Chemical Letters, ;2026, 37(8): 111818. doi: 10.1016/j.cclet.2025.111818 shu

Natural products self-assembling permeation enhancer for intestinal delivery of calcitonin

Runrui Liao ^{a, 1} ,
Huiling Zeng ^{a, 1} ,
Jiahui Zou ^a ,
Wei He ^{a, *,} ,
Hairong Wang ^{b, *,}

a.
School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
b.
School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China

weihe@cpu.edu.cn

18100977@hebmu.edu.cn

Received Date: 21 May 2025
Revised Date: 8 September 2025
Accepted Date: 9 September 2025
Available Online: 11 September 2025

Figures(5)

Calcitonin (CT), a 32-amino acid polypeptide drug, is crucial in regulating calcium homeostasis and inhibiting osteoclast activity. CT is primarily administered via injections and nasal sprays. However, injections usually suffer from poor patient compliance, while nasal sprays may cause side effects such as epistaxis, rhinitis, and nasal mucosal ulcers, coupled with low bioavailability. Deep eutectic solvents (DESs), formed by hydrogen-bond donors and acceptors, have shown potential in overcoming intestinal permeability barriers and facilitating the oral delivery of peptide drugs. Herein, we developed an intestinal drug delivery system for CT using DESs, which is expected to facilitate the subsequent development of oral preparations. We first prepared and characterized DESs with different stoichiometric ratios of choline (Ch) and geranate (Ge), followed by the investigation of the interaction between CT and Ch-Ge-based DESs (CAGE). Intestinal transport studies revealed that CAGE significantly promoted the jejunal absorption of CT-CAGE 1:2 (Ch and Ge in a 1:2 ratio), exhibiting the most pronounced pro-permeability effect. In vivo pharmacokinetic and pharmacodynamic results indicated that, compared with the aqueous CT solution, the CT-CAGE formulation increased bioavailability to 3.53%, with a significant hypocalcemic effect. In vitro studies further demonstrated that CAGE increased the transmembrane transport and membrane permeability of CT. The pro-permeability mechanism of CAGE may be related to the opening of tight junctions between intestinal cells and the improvement of paracellular transport efficiency. This DES-based drug delivery system offers a novel and promising approach for the oral delivery design of CT, addressing the limitations of administration routes.
- Calcitonin,
- Peptide drug,
- Deep eutectic solvent,
- Permeation enhancer,
- Oral delivery,
- Transmembrane transport
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