Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody

Tushar Kumeria; Joanna Wang; Byungji Kim; Ji Ho Park; Jonathan M. Zuidema; Mark Klempner; Lisa Cavacini; Yang Wang; Michael J. Sailor

doi:10.1021/acsbiomaterials.0c01313

Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody

Tushar Kumeria, Joanna Wang, Byungji Kim, Ji Ho Park, Jonathan M. Zuidema, Mark Klempner, Lisa Cavacini, Yang Wang, Michael J. Sailor

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Porous silicon (pSi) nanoparticles are loaded with Immunoglobulin A-2 (IgA2) antibodies, and the assembly is coated with pH-responsive polymers on the basis of the Eudragit family of enteric polymers (L100, S100, and L30-D55). The temporal release of the protein from the nanocomposite formulations is quantified following an in vitro protocol simulating oral delivery: incubation in simulated gastric fluid (SGF; at pH 1.2) for 2 h, followed by a fasting state simulated intestinal fluid (FasSIF; at pH 6.8) or phosphate buffer solution (PBS; at pH 7.4). The nanocomposite formulations display a negligible release in SGF, while more than 50% of the loaded IgA2 is released in solutions at a pH of 6.8 (FasSIF) or 7.4 (PBS). Between 21 and 44% of the released IgA2 retains its functional activity. A capsule-based system is also evaluated, where the IgA2-loaded particles are packed into a gelatin capsule and the capsule is coated with either EudragitL100 or EudragitS100 polymer for a targeted release in the small intestine or the colon, respectively. The capsule-based formulations outperform polymer-coated nanoparticles in vitro, preserving 45-54% of the activity of the released protein.

Original language	English
Pages (from-to)	4140-4152
Number of pages	13
Journal	ACS Biomaterials Science and Engineering
Volume	8
Issue number	10
DOIs	https://doi.org/10.1021/acsbiomaterials.0c01313
State	Published - Oct 10 2022

Bibliographical note

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

Funding

This project was funded in part by the National Institutes of Health (Grant R01 AI132413-01), by the National Science Foundation under grant CBET-1603177, by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement HR0011-13-2-0017, and by the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC), supported by the National Science Foundation (Grant DMR-2011924). The authors would like to acknowledge support to M.K. from the Defense Advanced Research Project Agency (DARPA-BAA-13-03). T.K. would like to thank the National Health and Medical Research Council of Australia for an Early Career Fellowship (GNT1143296) and the University of New South Wales-Sydney for a Scientia grant. J.W. would like to thank the National Institutes of Health for support from training grant T32 CA153915-06. This work was performed in part in the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS-1542148). The content of the information within this document does not necessarily reflect the position or the policy of the Government.

Funders	Funder number
National Health and Medical Research Council, Australia
UC San Diego Materials Research Science and Engineering Center
Australian National Drug and Alcohol Research Centre of the University of New South Wales Sydney	ECCS-1542148, T32 CA153915-06
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China	CBET-1603177
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China
National Institutes of Health (NIH)
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases	R01AI132413
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases
Defense Advanced Research Projects Agency	DARPA-BAA-13-03, HR0011-13-2-0017
Defense Advanced Research Projects Agency
Materials Research Science and Engineering Center, University of California, San Diego	DMR-2011924
Materials Research Science and Engineering Center, University of California, San Diego
Australian National Health and Medical Research Council	GNT1143296
Australian National Health and Medical Research Council

Keywords

biologic antibacterial therapeutics, Eudragit polymer
oral drug delivery
pH-responsive drug delivery

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering

Access to Document

10.1021/acsbiomaterials.0c01313

Cite this

@article{dba8547072fc4bdb82d829671c7fc9a9,

title = "Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody",

abstract = "Porous silicon (pSi) nanoparticles are loaded with Immunoglobulin A-2 (IgA2) antibodies, and the assembly is coated with pH-responsive polymers on the basis of the Eudragit family of enteric polymers (L100, S100, and L30-D55). The temporal release of the protein from the nanocomposite formulations is quantified following an in vitro protocol simulating oral delivery: incubation in simulated gastric fluid (SGF; at pH 1.2) for 2 h, followed by a fasting state simulated intestinal fluid (FasSIF; at pH 6.8) or phosphate buffer solution (PBS; at pH 7.4). The nanocomposite formulations display a negligible release in SGF, while more than 50\% of the loaded IgA2 is released in solutions at a pH of 6.8 (FasSIF) or 7.4 (PBS). Between 21 and 44\% of the released IgA2 retains its functional activity. A capsule-based system is also evaluated, where the IgA2-loaded particles are packed into a gelatin capsule and the capsule is coated with either EudragitL100 or EudragitS100 polymer for a targeted release in the small intestine or the colon, respectively. The capsule-based formulations outperform polymer-coated nanoparticles in vitro, preserving 45-54\% of the activity of the released protein.",

keywords = "biologic antibacterial therapeutics, Eudragit polymer, oral drug delivery, pH-responsive drug delivery",

author = "Tushar Kumeria and Joanna Wang and Byungji Kim and Park, \{Ji Ho\} and Zuidema, \{Jonathan M.\} and Mark Klempner and Lisa Cavacini and Yang Wang and Sailor, \{Michael J.\}",

year = "2022",

month = oct,

day = "10",

doi = "10.1021/acsbiomaterials.0c01313",

language = "English",

volume = "8",

pages = "4140--4152",

number = "10",

}

TY - JOUR

T1 - Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody

AU - Kumeria, Tushar

AU - Wang, Joanna

AU - Kim, Byungji

AU - Park, Ji Ho

AU - Zuidema, Jonathan M.

AU - Klempner, Mark

AU - Cavacini, Lisa

AU - Wang, Yang

AU - Sailor, Michael J.

PY - 2022/10/10

Y1 - 2022/10/10

N2 - Porous silicon (pSi) nanoparticles are loaded with Immunoglobulin A-2 (IgA2) antibodies, and the assembly is coated with pH-responsive polymers on the basis of the Eudragit family of enteric polymers (L100, S100, and L30-D55). The temporal release of the protein from the nanocomposite formulations is quantified following an in vitro protocol simulating oral delivery: incubation in simulated gastric fluid (SGF; at pH 1.2) for 2 h, followed by a fasting state simulated intestinal fluid (FasSIF; at pH 6.8) or phosphate buffer solution (PBS; at pH 7.4). The nanocomposite formulations display a negligible release in SGF, while more than 50% of the loaded IgA2 is released in solutions at a pH of 6.8 (FasSIF) or 7.4 (PBS). Between 21 and 44% of the released IgA2 retains its functional activity. A capsule-based system is also evaluated, where the IgA2-loaded particles are packed into a gelatin capsule and the capsule is coated with either EudragitL100 or EudragitS100 polymer for a targeted release in the small intestine or the colon, respectively. The capsule-based formulations outperform polymer-coated nanoparticles in vitro, preserving 45-54% of the activity of the released protein.

AB - Porous silicon (pSi) nanoparticles are loaded with Immunoglobulin A-2 (IgA2) antibodies, and the assembly is coated with pH-responsive polymers on the basis of the Eudragit family of enteric polymers (L100, S100, and L30-D55). The temporal release of the protein from the nanocomposite formulations is quantified following an in vitro protocol simulating oral delivery: incubation in simulated gastric fluid (SGF; at pH 1.2) for 2 h, followed by a fasting state simulated intestinal fluid (FasSIF; at pH 6.8) or phosphate buffer solution (PBS; at pH 7.4). The nanocomposite formulations display a negligible release in SGF, while more than 50% of the loaded IgA2 is released in solutions at a pH of 6.8 (FasSIF) or 7.4 (PBS). Between 21 and 44% of the released IgA2 retains its functional activity. A capsule-based system is also evaluated, where the IgA2-loaded particles are packed into a gelatin capsule and the capsule is coated with either EudragitL100 or EudragitS100 polymer for a targeted release in the small intestine or the colon, respectively. The capsule-based formulations outperform polymer-coated nanoparticles in vitro, preserving 45-54% of the activity of the released protein.

KW - biologic antibacterial therapeutics, Eudragit polymer

KW - oral drug delivery

KW - pH-responsive drug delivery

UR - http://www.scopus.com/inward/record.url?scp=85097874875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85097874875&partnerID=8YFLogxK

U2 - 10.1021/acsbiomaterials.0c01313

DO - 10.1021/acsbiomaterials.0c01313

M3 - Article

C2 - 36210772

AN - SCOPUS:85097874875

VL - 8

SP - 4140

EP - 4152

JO - ACS Biomaterials Science and Engineering

JF - ACS Biomaterials Science and Engineering

IS - 10

ER -

Enteric Polymer-Coated Porous Silicon Nanoparticles for Site-Specific Oral Delivery of IgA Antibody

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this