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
Abstract:
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
Author description:
Service
PDF(KB) Free
Print
0
Authors
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

References:
1. Ryter SW, Choi AM. Carbon monoxide:present and future indications for a medical gas. Korean J Intern Med 2013;28:123-40.
2. Zheng Y, Ji X, Ji K, Wang B. Hydrogen sulfide prodrugsda review. Acta Pharm Sin B 2015;5:367-77.
3. Rose JJ, Wang L, Xu Q, McTiernan CF, Shiva S, Tejero J, et al. Carbon monoxide poisoning:pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med 2017;195:596-606.
4. Piantadosi CA. Biological chemistry of carbon monoxide. Antioxidants Redox Signal 2002;4:259-70.
5. Motterlini R, Otterbein LE. The therapeutic potential of carbon monoxide. Nat Rev Drug Discov 2010;9:728-43.
6. Bauer I, Pannen BH. Bench-to-bedside review:carbon monoxide-from mitochondrial poisoning to therapeutic use. Crit Care 2009;13:220.
7. Abraham NG, Kappas A. Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev 2008;60:79-127.
8. Motterlini R, Mann BE, Foresti R. Therapeutic applications of carbon monoxide-releasing molecules. Expet Opin Invest Drugs 2005;14:1305-18.
9. Otterbein LE, Mantell LL, Choi AM. Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol 1999;276:L688-94.
10. Fujita T, Toda K, Karimova A, Yan SF, Naka Y, Yet SF, et al. Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 2001;7:598-604.
11. Foresti R, Bani-Hani MG, Motterlini R. Use of carbon monoxide as a therapeutic agent:promises and challenges. Intensive Care Med 2008; 34:649-58.
12. Otterbein LE, Zuckerbraun BS, Haga M, Liu F, Song R, Usheva A, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 2003;9:183-90.
13. Romão CC, Blättler WA, Seixas JD, Bernardes GJL. Developing drug molecules for therapy with carbon monoxide. Chem Soc Rev 2012;41:3571-83.
14. García-Gallego S, Bernardes GJ. Carbon-monoxide-releasing molecules for the delivery of therapeutic CO in vivo. Angew Chem 2014;53:9712-21.
15. Ismailova A, Kuter D, Bohle DS, Butler IS. An overview of the potential therapeutic applications of CO-releasing molecules. Bioinorgan Chem Appl 2018;2018:8547364.
16. Kourti M, Jiang WG, Cai J. Aspects of carbon monoxide in form of CO-releasing molecules used in cancer treatment:more light on the way. Oxid Med Cell Longev 2017;2017:9326454.
17. Wei Y, Chen P, de Bruyn M, Zhang W, Bremer E, Helfrich W. Carbon monoxide-releasing molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats. BMC Gastroenterol 2010;10:42.
18. Takagi T, Naito Y, Uchiyama K, Suzuki T, Hirata I, Mizushima K, et al. Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice. Dig Dis Sci 2011;56:1663-71.
19. Nobre LS, Seixas JD, Romao CC, Saraiva LM. Antimicrobial action of carbon monoxide-releasing compounds. Antimicrob Agents Chemother 2007;51:4303-7.
20. Yin H, Fang J, Liao L, Nakamura H, Maeda H. Styrene-maleic acid copolymer-encapsulated CORM2, a water-soluble carbon monoxide (CO) donor with a constant CO-releasing property, exhibits therapeutic potential for inflammatory bowel disease. J Control Release 2014;187:14-21.
21. Qureshi OS, Zeb A, Akram M, Kim M-S, Kang JH, Kim HS, et al. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery. Eur J Pharm Biopharm 2016;108:187-95.
22. Joshi HP, Kim SB, Kim S, Kumar H, Jo MJ, Choi H, et al. Nanocarrier-mediated delivery of CORM-2 enhances anti-allodynic and anti-hyperalgesic effects of CORM-2. Mol Neurobiol 2019;56:5539-54.
23. Zeb A, Arif ST, Malik M, Shah FA, Din FU, Qureshi OS, et al. Potential of nanoparticulate carriers for improved drug delivery via skin. J Pharm Investig 2019;49:485-517.
24. Maniyar MG, Kokare CR. Formulation and evaluation of spray dried liposomes of lopinavir for topical application. J Pharm Investig 2019; 49:259-70.
25. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Lipid vesicles for skin delivery of drugs:reviewing three decades of research. Int J Pharm 2007;332:1-16.
26. Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta 1992;1104:226-32.
27. Zeb A, Qureshi OS, Kim HS, Cha JH, Kim HS, Kim JK. Improved skin permeation of methotrexate via nanosized ultradeformable liposomes. Int J Nanomed 2016;11:3813.
28. Gupta PN, Mishra V, Rawat A, Dubey P, Mahor S, Jain S, et al. Noninvasive vaccine delivery in transfersomes, niosomes and liposomes:a comparative study. Int J Pharm 2005;293:73-82.
29. Zeb A, Cha JH, Noh AR, Qureshi OS, Kim KW, Choe YH, et al. Neuroprotective effects of carnosine-loaded elastic liposomes in cerebral ischemia rat model. J Pharm Investig 2020;50:373-81.
30. Hasegawa U, van der Vlies AJ, Simeoni E, Wandrey C, Hubbell JA. Carbon monoxide-releasing micelles for immunotherapy. J Am Chem Soc 2010;132:18273-80.
31. Akram M, Syed Ahmed S, Kim KA, Lee Jong S, Chang SY, Kim Chul Y, et al. Heme oxygenase 1-mediated novel anti-inflammatory activities of Salvia plebeia and its active components. J Ethnopharmacol 2015;174:322-30.
32. Akram M, Kim KA, Kim ES, Shin YJ, Noh D, Kim E, et al. Selective inhibition of JAK2/STAT1 signaling and iNOS expression mediates the anti-inflammatory effects of coniferyl aldehyde. Chem Biol Interact 2016;256:102-10.
33. Akram M, Shin I, Kim KA, Noh D, Baek SH, Chang SY, et al. A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation:the Nrf 2/heme oxygenase signaling as a potential target. Toxicol Appl Pharmacol 2016;307:62-71.
34. Bralley EE, Greenspan P, Hargrove JL, Wicker L, Hartle DK. Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation. J Inflamm 2008;5:1.
35. Chen J, Lu WL, Gu W, Lu SS, Chen ZP, Cai BC. Skin permeation behavior of elastic liposomes:role of formulation ingredients. Expet Opin Drug Deliv 2013;10:845-56.
36. Hussain A, Singh S, Sharma D, Webster TJ, Shafaat K, Faruk A. Elastic liposomes as novel carriers:recent advances in drug delivery. Int J Nanomed 2017;12:5087-108.
37. Duangjit S, Pamornpathomkul B, Opanasopit P, Rojanarata T, Obata Y, Takayama K, et al. Role of the charge, carbon chain length, and content of surfactant on the skin penetration of meloxicam-loaded liposomes. Int J Nanomed 2014;9:2005.
38. El Zaafarany GM, Awad GA, Holayel SM, Mortada ND. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int J Pharm 2010;397:164-72.
39. Cevc G, Blume G. Biological activity and characteristics of triamcinolone-acetonide formulated with the self-regulating drug carriers, Transfersomes. Biochim Biophys Acta 2003;1614:156-64.
40. Perez AP, Altube MJ, Schilrreff P, Apezteguia G, Celes FS, Zacchino S, et al. Topical amphotericin B in ultradeformable liposomes:formulation, skin penetration study, antifungal and antileishmanial activity in vitro. Colloids Surf B Biointerfaces 2016;139:190-8.
41. Cevc G. Rational design of new product candidates:the next generation of highly deformable bilayer vesicles for noninvasive, targeted therapy. J Control Release 2012;160:135-46.
42. Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J Control Release 2007;123:148-54.
43. Dubey V, Mishra D, Jain NK. Melatonin loaded ethanolic liposomes:physicochemical characterization and enhanced transdermal delivery. Eur J Pharm Biopharm 2007;67:398-405.
44. McLean S, Mann BE, Poole RK. Sulfite species enhance carbon monoxide release from CO-releasing molecules:implications for the deoxymyoglobin assay of activity. Anal Biochem 2012;427:36-40.
45. Sawle P, Foresti R, Mann BE, Johnson TR, Green CJ, Motterlini R. Carbon monoxide-releasing molecules (CO-RMs) attenuate the inflammatory response elicited by lipopolysaccharide in RAW264.7 murine macrophages. Br J Pharmacol 2005;145:800-10.
46. Otterbein LE, Bach FH, Alam J, Soares M, Lu HT, Wysk M, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6:422.
47. Taguchi K, Nagao S, Maeda H, Yanagisawa H, Sakai H, Yamasaki K, et al. Biomimetic carbon monoxide delivery based on hemoglobin vesicles ameliorates acute pancreatitis in mice via the regulation of macrophage and neutrophil activity. Drug Deliv 2018;25:1266-74.
48. Castro J, Rivera D, Franco LA. Topical anti-inflammatory activity in TPA-induced mouse ear edema model and in vitro antibacterial properties of Cordia alba flowers. J Pharm Investig 2019;49:331-6.
49. Yu WG, He H, Yao JY, Zhu YX, Lu YH. Dimethyl cardamonin exhibits anti-inflammatory effects via interfering with the PI3K-PDK1-PKCalpha signaling pathway. Biomol Ther 2015;23:549-56.
50. Cosco D, Paolino D, Maiuolo J, Di Marzio L, Carafa M, Ventura CA, et al. Ultradeformable liposomes as multidrug carrier of resveratrol and 5-fluorouracil for their topical delivery. Int J Pharm 2015;489:1-10.
51. Elsayed MMA, Abdallah OY, Naggar VF, Khalafallah NM. Deformable liposomes and ethosomes:mechanism of enhanced skin delivery. Int J Pharm 2006;322:60-6.
52. Benson HA. Transfersomes for transdermal drug delivery. Expet Opin Drug Deliv 2006;3:727-37.
53. Honeywell-Nguyen PL, Bouwstra JA. The in vitro transport of pergolide from surfactant-based elastic vesicles through human skin:a suggested mechanism of action. J Control Release 2003;86:145-56.
54. Kautz AC, Kunz PC, Janiak C. CO-releasing molecule (CORM) conjugate systems. Dalton Trans 2016;45:18045-63.
55. Markina M, Stozhko N, Krylov V, Vidrevich M, Brainina K. Nanoparticle-based paper sensor for thiols evaluation in human skin. Talanta 2017;165:563-9.
Similar articles: