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 | |
| 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 |
| National Science Foundation Arctic Social Science Program | CBET-1603177 |
| National Institutes of Health (NIH) | |
| National Institute of Allergy and Infectious Diseases | R01AI132413 |
| Defense Advanced Research Projects Agency | DARPA-BAA-13-03, HR0011-13-2-0017 |
| Materials Research Science and Engineering Center, University of California, San Diego | DMR-2011924 |
| Australian National Health and Medical Research Council | GNT1143296 |
Keywords
- biologic antibacterial therapeutics, Eudragit polymer
- oral drug delivery
- pH-responsive drug delivery
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering