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

Research output: Contribution to journalArticle

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

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.

Original languageEnglish (US)
Pages (from-to)61-72
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume151
Early online dateApr 10 2020
DOIs
StatePublished - Jun 1 2020

PMID: 32283213

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Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease. / Leonard, Fransisca; Srinivasan, Srimeenakshi; Liu, Xuewu; Collnot, Eva Maria; Ferrari, Mauro; Lehr, Claus Michael; Godin, Biana.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 151, 01.06.2020, p. 61-72.

Research output: Contribution to journalArticle

Harvard

Leonard, F, Srinivasan, S, Liu, X, Collnot, EM, Ferrari, M, Lehr, CM & Godin, B 2020, 'Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease' European Journal of Pharmaceutics and Biopharmaceutics, vol. 151, pp. 61-72. https://doi.org/10.1016/j.ejpb.2020.03.020

APA

Leonard, F., Srinivasan, S., Liu, X., Collnot, E. M., Ferrari, M., Lehr, C. M., & Godin, B. (2020). Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease. European Journal of Pharmaceutics and Biopharmaceutics, 151, 61-72. https://doi.org/10.1016/j.ejpb.2020.03.020

Vancouver

Leonard F, Srinivasan S, Liu X, Collnot EM, Ferrari M, Lehr CM et al. Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease. European Journal of Pharmaceutics and Biopharmaceutics. 2020 Jun 1;151:61-72. https://doi.org/10.1016/j.ejpb.2020.03.020

Author

Leonard, Fransisca ; Srinivasan, Srimeenakshi ; Liu, Xuewu ; Collnot, Eva Maria ; Ferrari, Mauro ; Lehr, Claus Michael ; Godin, Biana. / Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease. In: European Journal of Pharmaceutics and Biopharmaceutics. 2020 ; Vol. 151. pp. 61-72.

BibTeX

@article{77b4029d0c8c47ea8d57450ee59d1941,
title = "Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease",
abstract = "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.",
keywords = "Epithelial barrier, Glucocorticoid, Inflammation, Inflammatory bowel disease, Microparticles, Nanomedicine, Nanoparticles, Three dimensional tissue model",
author = "Fransisca Leonard and Srimeenakshi Srinivasan and Xuewu Liu and Collnot, {Eva Maria} and Mauro Ferrari and Lehr, {Claus Michael} and Biana Godin",
note = "Copyright {\circledC} 2020. Published by Elsevier B.V.",
year = "2020",
month = "6",
day = "1",
doi = "10.1016/j.ejpb.2020.03.020",
language = "English (US)",
volume = "151",
pages = "61--72",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Design and in vitro characterization of multistage silicon-PLGA budesonide particles for inflammatory bowel disease

AU - Leonard, Fransisca

AU - Srinivasan, Srimeenakshi

AU - Liu, Xuewu

AU - Collnot, Eva Maria

AU - Ferrari, Mauro

AU - Lehr, Claus Michael

AU - Godin, Biana

N1 - Copyright © 2020. Published by Elsevier B.V.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - 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.

AB - 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.

KW - Epithelial barrier

KW - Glucocorticoid

KW - Inflammation

KW - Inflammatory bowel disease

KW - Microparticles

KW - Nanomedicine

KW - Nanoparticles

KW - Three dimensional tissue model

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U2 - 10.1016/j.ejpb.2020.03.020

DO - 10.1016/j.ejpb.2020.03.020

M3 - Article

VL - 151

SP - 61

EP - 72

JO - European Journal of Pharmaceutics and Biopharmaceutics

T2 - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -

ID: 61559525