Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease

Copyright © 2020 Elsevier B.V. All rights reserved..

Inflammatory bowel disease (IBD) affects a confined area of the intestine and, therefore, administration of drugs via oral route is preferable. However, obstacles such as changes in the pH along gastrointestinal tract (GIT), enzymatic activity, and intraluminal pressure may cause low drug availability in the target tissue when delivered orally. Previous studies have pointed out the benefits of using micron-sized particles for targeting inflamed intestinal mucosa and nanoparticles for delivery of anti-inflammatory agents to the affected epithelial cells. We hypothesized that by combining the benefits of micro- and nano- particles, we could create a more efficient delivery system for budesonide, a glucocorticosteroid commonly used for anti-inflammatory IBD therapy. The aim of this study was to develop a novel multistage system for oral delivery designed to increase concentrations budesonidein the inflamed intestinal tissue. The multistage system consists of Stage 1 mesoporous silicon microparticles (S1MP) loaded with stage 2 poly-lactic-glycolic acid (PLGA) budesonide-encapsulating nanoparticles (BNP). BNP were efficiently loaded into S1MP (loading efficiency of 45.9 ± 14.8%) due to the large pore volume and high surface area of S1MP and exhibited controlled release profiles with enhanced drug dissolution rate in biologically relevant pHs. Due to the robustness in acidic pH and their geometry, S1MP protected the loaded budesonide in the acidic (gastric) pH with only 20% release. This allowed for the prolonged release of the BNP in the higher pH conditions (intestinal pH). The sustained release of BNP could facilitate accumulation in the inflamed tissue, enabling BNP to penetrate inflamed mucosa and release active budesonide to the target site. The multistage systems of S1MP and BNP were further evaluated in three-dimensional (3D) in vitro model of IBD and were found to (1) increase accumulation of BNP in the inflamed areas, (2) restore the barrier function of Caco-2 inflamed monolayer, and (3) significantly reduce pro-inflammatory cytokine release almost to the level of the healthy control.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:151

Enthalten in:

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V - 151(2020) vom: 10. Juni, Seite 61-72

Sprache:

Englisch

Beteiligte Personen:

Leonard, Fransisca [VerfasserIn]
Srinivasan, Srimeenakshi [VerfasserIn]
Liu, Xuewu [VerfasserIn]
Collnot, Eva-Maria [VerfasserIn]
Ferrari, Mauro [VerfasserIn]
Lehr, Claus-Michael [VerfasserIn]
Godin, Biana [VerfasserIn]

Links:

Volltext

Themen:

1SIA8062RS
51333-22-3
Anti-Inflammatory Agents
Budesonide
Delayed-Action Preparations
Drug Carriers
Epithelial barrier
Glucocorticoid
Inflammation
Inflammatory bowel disease
Journal Article
Microparticles
Nanomedicine
Nanoparticles
Polylactic Acid-Polyglycolic Acid Copolymer
Silicon
Three dimensional tissue model
Z4152N8IUI

Anmerkungen:

Date Completed 09.02.2021

Date Revised 09.02.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ejpb.2020.03.020

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308682416