Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of AntiDiabetic Peptides

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation. The final formulation showed a controlled and narrow size distribution. The pH-responsive matrix remained intact in acidic conditions, dissolving only in intestinal pH, resulting in a sustained release of the payload. The NPs presented high cytocompatibility, and increased levels of interaction with intestinal cells when functionalized with the Fc fragment, which was supported by the validation of the Fc fragment integrity after conjugation to the NPs. Finally, the Fc-conjugated NPs showed augmented GLP-1 permeability in an intestinal in vitro model. These results highlight the potential of microfluidics as an advanced technique for the preparation of multistage platforms for oral administration. Moreover, this study provides new insights on the potential of the FcRn transcytotic capacity for the development of targeted therapies.
Original languageEnglish
JournalACS Applied Materials & Interfaces
Volume10
Issue number51
Pages (from-to)44354–44367
Number of pages14
ISSN1944-8244
DOIs
Publication statusPublished - 7 Dec 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 317 Pharmacy

Cite this

@article{c3ce373f693b44b5aef0b8480b6aaaff,
title = "Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of AntiDiabetic Peptides",
abstract = "Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation. The final formulation showed a controlled and narrow size distribution. The pH-responsive matrix remained intact in acidic conditions, dissolving only in intestinal pH, resulting in a sustained release of the payload. The NPs presented high cytocompatibility, and increased levels of interaction with intestinal cells when functionalized with the Fc fragment, which was supported by the validation of the Fc fragment integrity after conjugation to the NPs. Finally, the Fc-conjugated NPs showed augmented GLP-1 permeability in an intestinal in vitro model. These results highlight the potential of microfluidics as an advanced technique for the preparation of multistage platforms for oral administration. Moreover, this study provides new insights on the potential of the FcRn transcytotic capacity for the development of targeted therapies.",
keywords = "317 Pharmacy",
author = "{Oliveira Martins}, {Joao Pedro} and Dongfei Liu and Flavia Fontana and {Almeida Ferreira}, {Monica Patricia} and {Rebelo Correia}, {Alexandra Maria} and Silvia Valentino and Kemell, {Marianna Leena} and Karina Moslova and Ermei M{\"a}kil{\"a} and Jarno Salonen and Hirvonen, {Jouni Tapio} and Bruno Sarmento and {Almeida Santos}, Helder",
year = "2018",
month = "12",
day = "7",
doi = "10.1021/acsami.8b20821",
language = "English",
volume = "10",
pages = "44354–44367",
journal = "ACS Applied Materials & Interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",
number = "51",

}

TY - JOUR

T1 - Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of AntiDiabetic Peptides

AU - Oliveira Martins, Joao Pedro

AU - Liu, Dongfei

AU - Fontana, Flavia

AU - Almeida Ferreira, Monica Patricia

AU - Rebelo Correia, Alexandra Maria

AU - Valentino, Silvia

AU - Kemell, Marianna Leena

AU - Moslova, Karina

AU - Mäkilä, Ermei

AU - Salonen, Jarno

AU - Hirvonen, Jouni Tapio

AU - Sarmento, Bruno

AU - Almeida Santos, Helder

PY - 2018/12/7

Y1 - 2018/12/7

N2 - Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation. The final formulation showed a controlled and narrow size distribution. The pH-responsive matrix remained intact in acidic conditions, dissolving only in intestinal pH, resulting in a sustained release of the payload. The NPs presented high cytocompatibility, and increased levels of interaction with intestinal cells when functionalized with the Fc fragment, which was supported by the validation of the Fc fragment integrity after conjugation to the NPs. Finally, the Fc-conjugated NPs showed augmented GLP-1 permeability in an intestinal in vitro model. These results highlight the potential of microfluidics as an advanced technique for the preparation of multistage platforms for oral administration. Moreover, this study provides new insights on the potential of the FcRn transcytotic capacity for the development of targeted therapies.

AB - Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation. The final formulation showed a controlled and narrow size distribution. The pH-responsive matrix remained intact in acidic conditions, dissolving only in intestinal pH, resulting in a sustained release of the payload. The NPs presented high cytocompatibility, and increased levels of interaction with intestinal cells when functionalized with the Fc fragment, which was supported by the validation of the Fc fragment integrity after conjugation to the NPs. Finally, the Fc-conjugated NPs showed augmented GLP-1 permeability in an intestinal in vitro model. These results highlight the potential of microfluidics as an advanced technique for the preparation of multistage platforms for oral administration. Moreover, this study provides new insights on the potential of the FcRn transcytotic capacity for the development of targeted therapies.

KW - 317 Pharmacy

U2 - 10.1021/acsami.8b20821

DO - 10.1021/acsami.8b20821

M3 - Article

VL - 10

SP - 44354

EP - 44367

JO - ACS Applied Materials & Interfaces

JF - ACS Applied Materials & Interfaces

SN - 1944-8244

IS - 51

ER -