Abstract
Orally administered antisense therapy has been introduced as an effective approach for treating cancer in the gastrointestinal tract. However, its practical application has been limited by the instability of oligonucleotides and their inefficient delivery. To overcome these problems, we synthesized size-dependent, oligonucleotide nanoparticle-patterned chitosan/phytic acid (ODN/CS/PA) capsules with protective shields via a three-step process of self-assembly, nanoparticle encapsulation, and shell formation. The multicompartmental capsule size and oligonucleotide nanoparticle-loading pattern were controlled by applying different potentials during the electrostatic extrusion process used for nanoparticle encapsulation. Over 95% of encapsulated oligonucleotides were protected from nuclease digestion (DNase I) and, depending on their size, showed 40-75% protection against simulated gastric fluid. Their controlled release from capsules correlated with the cellular delivery of released nanoparticles and the inhibition of protein expression in cancer cells. Specifically, large capsules showed approximately 32-fold greater delivery to cancer cells than nonencapsulated nanoparticles. We also confirmed delivery of oligonucleotide nanoparticles to the small intestine and colon of rats following oral administration. These findings demonstrate that the multicompartmental ODN/CS/PA capsules can facilitate efficient oral delivery of oligonucleotides for cancer treatment.
| Original language | English |
|---|---|
| Journal | ACS Biomaterials Science and Engineering |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Biomaterials
- Biomedical Engineering
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Nanoparticle-Patterned Multicompartmental Chitosan Capsules for Oral Delivery of Oligonucleotides. / Kim, Taehyung; Kim, Jeong Un; Yang, Kyungjik; Nam, Keonwook; Choe, Deokyeong; Kim, Eugene; Hong, Il Hwa; Song, Minjung; Lee, Hyunah; Park, Jiyong; Roh, Young Hoon.
In: ACS Biomaterials Science and Engineering, 01.01.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - Nanoparticle-Patterned Multicompartmental Chitosan Capsules for Oral Delivery of Oligonucleotides
AU - Kim, Taehyung
AU - Kim, Jeong Un
AU - Yang, Kyungjik
AU - Nam, Keonwook
AU - Choe, Deokyeong
AU - Kim, Eugene
AU - Hong, Il Hwa
AU - Song, Minjung
AU - Lee, Hyunah
AU - Park, Jiyong
AU - Roh, Young Hoon
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Orally administered antisense therapy has been introduced as an effective approach for treating cancer in the gastrointestinal tract. However, its practical application has been limited by the instability of oligonucleotides and their inefficient delivery. To overcome these problems, we synthesized size-dependent, oligonucleotide nanoparticle-patterned chitosan/phytic acid (ODN/CS/PA) capsules with protective shields via a three-step process of self-assembly, nanoparticle encapsulation, and shell formation. The multicompartmental capsule size and oligonucleotide nanoparticle-loading pattern were controlled by applying different potentials during the electrostatic extrusion process used for nanoparticle encapsulation. Over 95% of encapsulated oligonucleotides were protected from nuclease digestion (DNase I) and, depending on their size, showed 40-75% protection against simulated gastric fluid. Their controlled release from capsules correlated with the cellular delivery of released nanoparticles and the inhibition of protein expression in cancer cells. Specifically, large capsules showed approximately 32-fold greater delivery to cancer cells than nonencapsulated nanoparticles. We also confirmed delivery of oligonucleotide nanoparticles to the small intestine and colon of rats following oral administration. These findings demonstrate that the multicompartmental ODN/CS/PA capsules can facilitate efficient oral delivery of oligonucleotides for cancer treatment.
AB - Orally administered antisense therapy has been introduced as an effective approach for treating cancer in the gastrointestinal tract. However, its practical application has been limited by the instability of oligonucleotides and their inefficient delivery. To overcome these problems, we synthesized size-dependent, oligonucleotide nanoparticle-patterned chitosan/phytic acid (ODN/CS/PA) capsules with protective shields via a three-step process of self-assembly, nanoparticle encapsulation, and shell formation. The multicompartmental capsule size and oligonucleotide nanoparticle-loading pattern were controlled by applying different potentials during the electrostatic extrusion process used for nanoparticle encapsulation. Over 95% of encapsulated oligonucleotides were protected from nuclease digestion (DNase I) and, depending on their size, showed 40-75% protection against simulated gastric fluid. Their controlled release from capsules correlated with the cellular delivery of released nanoparticles and the inhibition of protein expression in cancer cells. Specifically, large capsules showed approximately 32-fold greater delivery to cancer cells than nonencapsulated nanoparticles. We also confirmed delivery of oligonucleotide nanoparticles to the small intestine and colon of rats following oral administration. These findings demonstrate that the multicompartmental ODN/CS/PA capsules can facilitate efficient oral delivery of oligonucleotides for cancer treatment.
UR - http://www.scopus.com/inward/record.url?scp=85058104004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058104004&partnerID=8YFLogxK
U2 - 10.1021/acsbiomaterials.8b00806
DO - 10.1021/acsbiomaterials.8b00806
M3 - Article
AN - SCOPUS:85058104004
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
SN - 2373-9878
ER -