Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers

Neha Shrestha, Mohammad-Ali Shahbazi, Francisca Araújo, Hongbo Zhang, Ermei M. Mäkilä, Jussi Kauppila, Bruno Sarmento, Jarno J. Salonen, Jouni T. Hirvonen, Hélder A. Santos

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.
Original languageEnglish
JournalBiomaterials
Volume35
Issue number25
Pages (from-to)7172-7179
Number of pages8
ISSN0142-9612
DOIs
Publication statusPublished - 17 May 2014
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 216 Materials engineering
  • 318 Medical biotechnology
  • 317 Pharmacy
  • Porous silicon
  • Insulin
  • Diabetes
  • Chitosan
  • Cell monolayers
  • Microparticles

Cite this

Shrestha, Neha ; Shahbazi, Mohammad-Ali ; Araújo, Francisca ; Zhang, Hongbo ; Mäkilä, Ermei M. ; Kauppila, Jussi ; Sarmento, Bruno ; Salonen, Jarno J. ; Hirvonen, Jouni T. ; Santos, Hélder A. / Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers. In: Biomaterials. 2014 ; Vol. 35, No. 25. pp. 7172-7179.
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abstract = "Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.",
keywords = "216 Materials engineering, 318 Medical biotechnology, 317 Pharmacy, Porous silicon, Insulin, Diabetes, Chitosan, Cell monolayers, Microparticles",
author = "Neha Shrestha and Mohammad-Ali Shahbazi and Francisca Ara{\'u}jo and Hongbo Zhang and M{\"a}kil{\"a}, {Ermei M.} and Jussi Kauppila and Bruno Sarmento and Salonen, {Jarno J.} and Hirvonen, {Jouni T.} and Santos, {H{\'e}lder A.}",
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Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers. / Shrestha, Neha; Shahbazi, Mohammad-Ali; Araújo, Francisca ; Zhang, Hongbo; Mäkilä, Ermei M.; Kauppila, Jussi ; Sarmento, Bruno; Salonen, Jarno J.; Hirvonen, Jouni T.; Santos, Hélder A.

In: Biomaterials, Vol. 35, No. 25, 17.05.2014, p. 7172-7179.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers

AU - Shrestha, Neha

AU - Shahbazi, Mohammad-Ali

AU - Araújo, Francisca

AU - Zhang, Hongbo

AU - Mäkilä, Ermei M.

AU - Kauppila, Jussi

AU - Sarmento, Bruno

AU - Salonen, Jarno J.

AU - Hirvonen, Jouni T.

AU - Santos, Hélder A.

PY - 2014/5/17

Y1 - 2014/5/17

N2 - Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.

AB - Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (Papp) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.

KW - 216 Materials engineering

KW - 318 Medical biotechnology

KW - 317 Pharmacy

KW - Porous silicon

KW - Insulin

KW - Diabetes

KW - Chitosan

KW - Cell monolayers

KW - Microparticles

U2 - 10.1016/j.biomaterials.2014.04.104

DO - 10.1016/j.biomaterials.2014.04.104

M3 - Article

VL - 35

SP - 7172

EP - 7179

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

IS - 25

ER -