Hexapeptide-conjugated calcitonin for targeted therapy of osteoporosis.
J Control Release
; 304: 39-50, 2019 06 28.
Article
en En
| MEDLINE
| ID: mdl-31054990
ABSTRACT
The high level of bone metabolism associated with osteopenia and multifocal skeletal fracture remains a challenging clinical problem in osteoporosis patients. Salmon calcitonin (sCT), as a peptide medicine, is able to inhibit osteoclast activity and stimulate osteoblast growth. However, calcitonin receptors (CTRs) are widely distributed in vivo, limiting the specificity and therapeutic effects. Here, we report a bone-seeking hexapeptide (Asp6)-conjugated sCT (sCT-Mal-Asp6) for the targeted treatment of osteoporosis. The sCT-Mal-Asp6 was synthesized via a disulfide re-bridge reaction with high specificity and purity. It was demonstrated that the adsorption of sCT-Mal-Asp6 on hydroxyapatite (HA) was about 5.4 times higher than that of sCT. It was demonstrated a prolonged circulation time and 3-fold higher femur tissue accumulation of sCT-Mal-Asp6. In ovariectomized (OVX) models, sCT-Mal-Asp6 significantly increased the ability to attenuate hypercalcemia and reconstruct the trabecula. Our work provides an efficient approach to targeted and effective osteoporosis treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoporosis
/
Calcitonina
/
Sistemas de Liberación de Medicamentos
/
Conservadores de la Densidad Ósea
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China