Original articles
Gwan-Yeong Lee, Alam Zeb, Eun-Hye Kim, Beomseon Suh, Young-Jun Shin, Donghyun Kim, Kyoung-Won Kim, Yeong-Hwan Choe, Ho-Ik Choi, Cheol-Ho Lee, Omer Salman Qureshi, In-Bo Han, Sun-Young Chang, Ok-Nam Bae, Jin-Ki Kim. CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model via effective CO delivery[J]. Acta Pharmaceutica Sinica B, 2020, 10(12): 2362-2373

CORM-2-entrapped ultradeformable liposomes ameliorate acute skin inflammation in an ear edema model via effective CO delivery
Gwan-Yeong Leea, Alam Zeba,b, Eun-Hye Kima, Beomseon Suha, Young-Jun Shina, Donghyun Kima, Kyoung-Won Kima, Yeong-Hwan Choea, Ho-Ik Choia, Cheol-Ho Leea, Omer Salman Qureshic, In-Bo Hand, Sun-Young Change, Ok-Nam Baea, Jin-Ki Kima
a College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea;
b Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan;
c Department of Pharmacy, Forman Christian College, Lahore 54600, Pakistan;
d Department of Neurosurgery, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam 13496, Republic of Korea;
e College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2- UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay. In vitro and in vivo anti-inflammatory effects of CORM-2-UDLs were assessed in lipopolysaccharide-stimulated macrophages and TPA-induced ear edema model, respectively. The deformability of the optimized CORM-2-UDLs was 2.3 times higher than conventional liposomes. CORM-2-UDLs significantly prolonged the release half-life of CO from 30 s in a CORM-2 solution to 21.6 min. CORM-2-UDLs demonstrated in vitro anti-inflammatory activity by decreasing nitrite production and pro-inflammatory cytokine levels. Furthermore, CORM-2-UDLs successfully ameliorated skin inflammation by reducing ear edema, pathological scores, neutrophil accumulation, and inflammatory cytokines expression. The results demonstrate that CORM-2-UDLs could be used as promising therapeutics against acute skin inflammation.
Key words:    Carbon monoxide    CORM-2    Anti-inflammatory effect    Ultradeformable liposomes    Skin inflammation    Ear edema   
Received: 2020-03-28     Revised: 2020-05-16
DOI: 10.1016/j.apsb.2020.05.010
Funds: This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1A2B4006458).
Corresponding author: Ok-Nam Bae, onbae@hanyang.ac.kr;Jin-Ki Kim, jinkikim@hanyang.ac.kr     Email:onbae@hanyang.ac.kr;jinkikim@hanyang.ac.kr
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Gwan-Yeong Lee
Alam Zeb
Eun-Hye Kim
Beomseon Suh
Young-Jun Shin
Donghyun Kim
Kyoung-Won Kim
Yeong-Hwan Choe
Ho-Ik Choi
Cheol-Ho Lee
Omer Salman Qureshi
In-Bo Han
Sun-Young Chang
Ok-Nam Bae
Jin-Ki Kim

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