Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection
A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication met...
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doaj-0a1226d3693f4172af28ec5f58a8e9232020-11-25T02:18:33ZengMDPI AGPharmaceutics1999-49232019-08-0111841910.3390/pharmaceutics11080419pharmaceutics11080419Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular InjectionMyoung Jin Ho0Hoe Taek Jeong1Sung Hyun Im2Hyung Tae Kim3Jeong Eun Lee4Jun Soo Park5Ha Ra Cho6Dong Yoon Kim7Young Wook Choi8Joon Woo Lee9Yong Seok Choi10Myung Joo Kang11College of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Chung-Ang University, 84, Heukseok-ro, Dongjak-gu, Seoul 06974, KoreaDepartment of Radiology, Seoul National University Bundang Hospital, 82, Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaCollege of Pharmacy, Dankook University, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungcheongnam-do 31116, KoreaA novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic-<i>co</i>-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.<sup>®</sup>), or even 7.2 μm-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with <50% systemic exposure compared to that with the marketed product. The novel MS was physicochemically stable, with no changes in drug crystallinity and release profile over 12 months. Therefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with osteoarthritis, with reduced IA dosing frequency.https://www.mdpi.com/1999-4923/11/8/419triamcinolone acetonidemicrocrystalPLGA microspherelocal deliveryspray-drying techniqueintra-articular injectionjoint retentionsystemic exposure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Myoung Jin Ho Hoe Taek Jeong Sung Hyun Im Hyung Tae Kim Jeong Eun Lee Jun Soo Park Ha Ra Cho Dong Yoon Kim Young Wook Choi Joon Woo Lee Yong Seok Choi Myung Joo Kang |
spellingShingle |
Myoung Jin Ho Hoe Taek Jeong Sung Hyun Im Hyung Tae Kim Jeong Eun Lee Jun Soo Park Ha Ra Cho Dong Yoon Kim Young Wook Choi Joon Woo Lee Yong Seok Choi Myung Joo Kang Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection Pharmaceutics triamcinolone acetonide microcrystal PLGA microsphere local delivery spray-drying technique intra-articular injection joint retention systemic exposure |
author_facet |
Myoung Jin Ho Hoe Taek Jeong Sung Hyun Im Hyung Tae Kim Jeong Eun Lee Jun Soo Park Ha Ra Cho Dong Yoon Kim Young Wook Choi Joon Woo Lee Yong Seok Choi Myung Joo Kang |
author_sort |
Myoung Jin Ho |
title |
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection |
title_short |
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection |
title_full |
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection |
title_fullStr |
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection |
title_full_unstemmed |
Design and In Vivo Pharmacokinetic Evaluation of Triamcinolone Acetonide Microcrystals-Loaded PLGA Microsphere for Increased Drug Retention in Knees after Intra-Articular Injection |
title_sort |
design and in vivo pharmacokinetic evaluation of triamcinolone acetonide microcrystals-loaded plga microsphere for increased drug retention in knees after intra-articular injection |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2019-08-01 |
description |
A novel polymeric microsphere (MS) containing micronized triamcinolone acetonide (TA) in a crystalline state was structured to provide extended drug retention in joints after intra-articular (IA) injection. Microcrystals with a median diameter of 1.7 μm were prepared by ultra-sonication method, and incorporated into poly(lactic-<i>co</i>-glycolic acid)/poly(lactic acid) (PLGA/PLA) MSs using spray-drying technique. Cross-sectional observation and X-ray diffraction analysis showed that drug microcrystals were evenly embedded in the MSs, with a distinctive crystalline nature of TA. In vitro drug release from the novel MSs was markedly decelerated compared to those from the marketed crystalline suspension (Triam inj.<sup>®</sup>), or even 7.2 μm-sized TA crystals-loaded MSs. The novel system offered prolonged drug retention in rat joints, providing quantifiable TA remains over 28 days. Whereas, over 95% of IA TA was removed from joints within seven days, after injection of the marketed product. Systemic exposure of the steroidal compound was drastically decreased with the MSs, with <50% systemic exposure compared to that with the marketed product. The novel MS was physicochemically stable, with no changes in drug crystallinity and release profile over 12 months. Therefore, the TA microcrystals-loaded MS is expected to be beneficial in patients especially with osteoarthritis, with reduced IA dosing frequency. |
topic |
triamcinolone acetonide microcrystal PLGA microsphere local delivery spray-drying technique intra-articular injection joint retention systemic exposure |
url |
https://www.mdpi.com/1999-4923/11/8/419 |
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