New study helps pave the way for orally administered biological drugs

2023-04-21

In a new article, Benyamin Naranjani and Per Larsson of SweDeliver, show that decreased peristaltic wave speed can increase the maximum concentration of permeation enhancers and macromolecules at the epithelial surface with 397 and 380 percent respectively.

Benyamin Naranjani, PhD Student at SweDeliver and Uppsala University
Benyamin Naranjani, PhD Student at SweDeliver and Uppsala University

Biological drugs are becoming increasingly important in drug discovery and development, with more than 170 therapeutic peptides currently in clinical development. To achieve therapeutically relevant bioavailability values, most proteins and peptide drugs are administered parenterally to bypass the physiological barriers in alternative drug delivery routes. But with oral administration often being more patient-friendly with increased compliance, formulations enabling this would be of obvious benefit.

Per Larsson, Associate Professor
Per Larsson, Associate Professor

In a new study, PhD Student Benyamin Naranjani and Associate Professor Per Larsson of SweDeliver have – together with Patrick D. Sinko and Shakhawath Hossain – at Uppsala University's Department of Pharmacy, simulated intestinal peristalsis to map the intraluminal transport of macromolecules and permeation enhancers. A 29.75 cm segment of the small intestine was modeled, with varying peristaltic speed, pocket size, release location and occlusion ratio of the peristaltic wave to study the effect on drug transport.

"We observed that reaching therapeutically relevant concentrations of permeation enhancers at the epithelium surface is possible but that it depends on the characteristics of the intestinal peristaltic motility, such as wave speed and contraction strength. When we increased the wave speed or reduced the contraction strength in our model, the concentration of both the macromolecule and the permeation enhancer approached zero,” states Benyamin Naranjani.

The results suggest that a slower-moving and more contracted peristaltic wave leads to higher efficiency in transporting mass to the epithelial wall during the peristalsis phases of the migrating motor complex. The study is published in the International Journal of Biological Macromolecules.

illustration of research

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FACTS

  • SweDeliver is a national competence center in drug delivery.
  • With Uppsala University's Faculty of Pharmacy as the academic hub and 16 industrial partners, SweDeliver conducts research on parenteral, oral and pulmonary administration.

CONTACT

Benyamin NaranjaniBenyamin Naranjani, PhD Student
Department of Pharmacy
benyamin.naranjani@farmaci.uu.se

Per LarssonPer Larsson, Associate Professor
Department of Pharmacy
per.r.larsson@uu.se

text: Magnus Alsne, photo: Mikael Wallerstedt

Currently at SweDeliver

Last modified: 2022-11-16