Oral Delivery of Parathyroid Hormone Using a Triple-Padlock Nanocarrier for Osteoporosis via an Enterohepatic Circulation Pathway

ACS Appl Mater Interfaces. 2021 May 26;13(20):23314-23327. doi: 10.1021/acsami.0c22170. Epub 2021 Feb 15.

Abstract

Intermittent subcutaneous (S.C.) injection of teriparatide [PTH (1-34)] is one of the effective therapies to cure osteoporosis. However, a long-term repeated administration of teriparatide by S.C. to the patients is highly challenging. Herein, a triple padlock nanocarrier prepared by a taurocholic acid-conjugated chondroitin sulfate A (TCSA) is designed to develop an oral dosage form of recombinant human teriparatide (rhPTH). Oral administration of TCSA/rhPTH to the bilateral ovariectomized (OVX) rats resulted in the recovery of the bone marrow density and healthy serum bone parameters from the severe osteoporotic conditions. Also, it enhanced new bone formation in the osteoporotic tibias. This triple padlock oral delivery platform overcame the current barriers associated with teriparatide administration and exhibited a promising therapeutic effect against osteoporosis.

Keywords: and enterohepatic recycling pathway; nanoparticle; oral delivery; osteoporosis; parathyroid hormone.

MeSH terms

  • Administration, Oral
  • Animals
  • Bone and Bones / drug effects
  • Bone and Bones / physiology
  • Chondroitin Sulfates / chemistry
  • Drug Carriers* / administration & dosage
  • Drug Carriers* / chemistry
  • Drug Carriers* / pharmacokinetics
  • Enterohepatic Circulation / physiology*
  • Female
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Nanoparticles* / administration & dosage
  • Nanoparticles* / chemistry
  • Nanoparticles* / metabolism
  • Osteoblasts / drug effects
  • Osteoporosis / metabolism*
  • Ovariectomy
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacokinetics
  • Taurocholic Acid / chemistry
  • Teriparatide* / administration & dosage
  • Teriparatide* / pharmacokinetics
  • Teriparatide* / pharmacology

Substances

  • Drug Carriers
  • Recombinant Proteins
  • Teriparatide
  • Taurocholic Acid
  • Chondroitin Sulfates