Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice
MT-102 is a new anti-inflammatory agent derived from <i>Juglans mandshurica</i> and <i>Isatis indigotica</i>. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug d...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/12/2720 |
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| author | Kshitis Chandra Baral Sang Hoon Lee Jae Geun Song Seong Hoon Jeong Hyo-Kyung Han |
| author_facet | Kshitis Chandra Baral Sang Hoon Lee Jae Geun Song Seong Hoon Jeong Hyo-Kyung Han |
| author_sort | Kshitis Chandra Baral |
| collection | DOAJ |
| description | MT-102 is a new anti-inflammatory agent derived from <i>Juglans mandshurica</i> and <i>Isatis indigotica</i>. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis. Solubility assessment in different oils, surfactants, and cosurfactants led to a SMEDDS formulation of MT-102 using Capmul MCM, Tween 80, and propylene glycol. Based on a pseudoternary phase diagram, the optimal SMEDDS composition was selected, which consisted of 15% Capmul MCM, 42.5% Tween 80, and 42.5% propylene glycol. The resulting optimized SMEDDS (SMEDDS-F1) exhibited a narrow size distribution (177.5 ± 2.80 nm) and high indirubin content (275 ± 5.58 µg/g, a biomarker). Across an acidic to neutral pH range, SMEDDS-F1 showed rapid and extensive indirubin release, with dissolution rates approximately 15-fold higher than pure MT-102. Furthermore, oral administration of SMEDDS-F1 effectively mitigated inflammatory progression and symptoms in a mouse model of ulcerative colitis, whereas pure MT-102 was ineffective. SMEDDS-F1 minimized body weight loss (less than 5%) without any significant change in colon length and the morphology of colonic tissues, compared to those of the healthy control group. In addition, oral administration of SMEDDS-F1 significantly inhibited the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. In conclusion, the SMEDDS-F1 formulation employing Capmul MCM, Tween 80, and propylene glycol (15:42.5:42.5, <i>w</i>/<i>w</i>) enhances the solubility and therapeutic efficacy of MT-102. |
| first_indexed | 2024-03-08T20:27:03Z |
| format | Article |
| id | doaj.art-813d476040d44299af71256a13db1716 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T20:27:03Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-813d476040d44299af71256a13db17162023-12-22T14:32:07ZengMDPI AGPharmaceutics1999-49232023-12-011512272010.3390/pharmaceutics15122720Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis MiceKshitis Chandra Baral0Sang Hoon Lee1Jae Geun Song2Seong Hoon Jeong3Hyo-Kyung Han4College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaCollege of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of KoreaMT-102 is a new anti-inflammatory agent derived from <i>Juglans mandshurica</i> and <i>Isatis indigotica</i>. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis. Solubility assessment in different oils, surfactants, and cosurfactants led to a SMEDDS formulation of MT-102 using Capmul MCM, Tween 80, and propylene glycol. Based on a pseudoternary phase diagram, the optimal SMEDDS composition was selected, which consisted of 15% Capmul MCM, 42.5% Tween 80, and 42.5% propylene glycol. The resulting optimized SMEDDS (SMEDDS-F1) exhibited a narrow size distribution (177.5 ± 2.80 nm) and high indirubin content (275 ± 5.58 µg/g, a biomarker). Across an acidic to neutral pH range, SMEDDS-F1 showed rapid and extensive indirubin release, with dissolution rates approximately 15-fold higher than pure MT-102. Furthermore, oral administration of SMEDDS-F1 effectively mitigated inflammatory progression and symptoms in a mouse model of ulcerative colitis, whereas pure MT-102 was ineffective. SMEDDS-F1 minimized body weight loss (less than 5%) without any significant change in colon length and the morphology of colonic tissues, compared to those of the healthy control group. In addition, oral administration of SMEDDS-F1 significantly inhibited the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. In conclusion, the SMEDDS-F1 formulation employing Capmul MCM, Tween 80, and propylene glycol (15:42.5:42.5, <i>w</i>/<i>w</i>) enhances the solubility and therapeutic efficacy of MT-102.https://www.mdpi.com/1999-4923/15/12/2720solubilityinflammationself-microemulsifying drug delivery systemoral efficacy |
| spellingShingle | Kshitis Chandra Baral Sang Hoon Lee Jae Geun Song Seong Hoon Jeong Hyo-Kyung Han Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice Pharmaceutics solubility inflammation self-microemulsifying drug delivery system oral efficacy |
| title | Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice |
| title_full | Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice |
| title_fullStr | Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice |
| title_full_unstemmed | Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice |
| title_short | Improved Therapeutic Efficacy of MT102, a New Anti-Inflammatory Agent, via a Self-Microemulsifying Drug Delivery System, in Ulcerative Colitis Mice |
| title_sort | improved therapeutic efficacy of mt102 a new anti inflammatory agent via a self microemulsifying drug delivery system in ulcerative colitis mice |
| topic | solubility inflammation self-microemulsifying drug delivery system oral efficacy |
| url | https://www.mdpi.com/1999-4923/15/12/2720 |
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