Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages
Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanopa...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/10/2118 |
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| author | Shwe Phyu Hlaing Jiafu Cao Juho Lee Jihyun Kim Aruzhan Saparbayeva Dongmin Kwak Hyunwoo Kim Seonghwan Hwang Hwayoung Yun Hyung Ryong Moon Yunjin Jung Jin-Wook Yoo |
| author_facet | Shwe Phyu Hlaing Jiafu Cao Juho Lee Jihyun Kim Aruzhan Saparbayeva Dongmin Kwak Hyunwoo Kim Seonghwan Hwang Hwayoung Yun Hyung Ryong Moon Yunjin Jung Jin-Wook Yoo |
| author_sort | Shwe Phyu Hlaing |
| collection | DOAJ |
| description | Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis. |
| first_indexed | 2024-03-09T19:35:31Z |
| format | Article |
| id | doaj.art-5486f6ca7c3748b68907a2c5f4eddb62 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T19:35:31Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5486f6ca7c3748b68907a2c5f4eddb622023-11-24T01:56:19ZengMDPI AGPharmaceutics1999-49232022-10-011410211810.3390/pharmaceutics14102118Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and MacrophagesShwe Phyu Hlaing0Jiafu Cao1Juho Lee2Jihyun Kim3Aruzhan Saparbayeva4Dongmin Kwak5Hyunwoo Kim6Seonghwan Hwang7Hwayoung Yun8Hyung Ryong Moon9Yunjin Jung10Jin-Wook Yoo11College of Pharmacy, Pusan National University, Busan 46241, KoreaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy, Pusan National University, Busan 46241, KoreaAlthough various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HA-CD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGA-NPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis.https://www.mdpi.com/1999-4923/14/10/2118ulcerative colitis therapyinflamed tissue targetingmacrophage targetingnanoparticlehyaluronic acid |
| spellingShingle | Shwe Phyu Hlaing Jiafu Cao Juho Lee Jihyun Kim Aruzhan Saparbayeva Dongmin Kwak Hyunwoo Kim Seonghwan Hwang Hwayoung Yun Hyung Ryong Moon Yunjin Jung Jin-Wook Yoo Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages Pharmaceutics ulcerative colitis therapy inflamed tissue targeting macrophage targeting nanoparticle hyaluronic acid |
| title | Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages |
| title_full | Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages |
| title_fullStr | Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages |
| title_full_unstemmed | Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages |
| title_short | Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages |
| title_sort | hyaluronic acid conjugated plga nanoparticles alleviate ulcerative colitis via cd44 mediated dual targeting to inflamed colitis tissue and macrophages |
| topic | ulcerative colitis therapy inflamed tissue targeting macrophage targeting nanoparticle hyaluronic acid |
| url | https://www.mdpi.com/1999-4923/14/10/2118 |
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