Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration
As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitatio...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/11/561 |
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| author | Pooja Maharjan Daseul Kim Minki Jin Hwi Jin Ko Yeong Ho Song Yoonjin Lee Byul-Nim Ahn Si-Kyung Kim Yujin Lee Meong Cheol Shin Kyoung Ah Min JaeWook Yang |
| author_facet | Pooja Maharjan Daseul Kim Minki Jin Hwi Jin Ko Yeong Ho Song Yoonjin Lee Byul-Nim Ahn Si-Kyung Kim Yujin Lee Meong Cheol Shin Kyoung Ah Min JaeWook Yang |
| author_sort | Pooja Maharjan |
| collection | DOAJ |
| description | As a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T12:10:33Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2fa5d83a64804fca843dc33396c881872022-12-22T04:24:37ZengMDPI AGPharmaceutics1999-49232019-10-01111156110.3390/pharmaceutics11110561pharmaceutics11110561Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular DegenerationPooja Maharjan0Daseul Kim1Minki Jin2Hwi Jin Ko3Yeong Ho Song4Yoonjin Lee5Byul-Nim Ahn6Si-Kyung Kim7Yujin Lee8Meong Cheol Shin9Kyoung Ah Min10JaeWook Yang11College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, KoreaResearch Institute, Yoo’s Biopharm Inc., 96 Gamasan-ro, Geumcheon-gu, Seoul 08501, KoreaResearch Institute, Yoo’s Biopharm Inc., 96 Gamasan-ro, Geumcheon-gu, Seoul 08501, KoreaT2B infrastructure center for ocular diseases, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, KoreaT2B infrastructure center for ocular diseases, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, KoreaT2B infrastructure center for ocular diseases, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, KoreaT2B infrastructure center for ocular diseases, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam 52828, KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, KoreaT2B infrastructure center for ocular diseases, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, KoreaAs a posterior ocular disease, wet age-related macular degeneration (WAMD) has been known to be related to vision loss, accompanying ocular complications. The intravitreous injection of VEGF antibodies has been reported to be an effective treatment to relieve symptoms of WAMD. However, the limitations of this treatment are high costs and invasiveness. For this reason, oral delivery route can be considered as a cost-effective way and the safest method to deliver drug molecules to the eyes. Accordingly, ursodeoxycholic acid (UDCA) was included in the oral formulation as the potential substance for the cure of WAMD in the animal model. Various pharmacological activities, such as antioxidant or anti-inflammatory effects, have been reported for UDCA and recent reports support the effects of UDCA in ocular treatment. However, due to poor water solubility and low pKa (around 5.0), it has been challenging to formulate aqueous solution of UDCA in the neutral pH range. In the present study, we confirmed the aqueous solubility of the oral UDCA formulation and performed a preclinical study, including pharmacokinetic profiling and WAMD model efficacy study in mice after oral administration of the drug solution. The results demonstrated that the formulation improved bioavailability of UDCA and efficiently delivered UDCA to the eye tissues after oral absorption. UDCA formulation was found to have inhibitory effects of choroidal neovascularization with a functional recovery in mice retinas. Taken together, our results suggest that the oral UDCA formulation could be used as a potent supplement for the cure of WAMD and related retinal diseases.https://www.mdpi.com/1999-4923/11/11/561ocular treatmentursodeoxycholic acidtauroursodeoxycholic acidbile acidage-related macular degenerationchoroidal neovascularization |
| spellingShingle | Pooja Maharjan Daseul Kim Minki Jin Hwi Jin Ko Yeong Ho Song Yoonjin Lee Byul-Nim Ahn Si-Kyung Kim Yujin Lee Meong Cheol Shin Kyoung Ah Min JaeWook Yang Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration Pharmaceutics ocular treatment ursodeoxycholic acid tauroursodeoxycholic acid bile acid age-related macular degeneration choroidal neovascularization |
| title | Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration |
| title_full | Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration |
| title_fullStr | Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration |
| title_full_unstemmed | Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration |
| title_short | Preclinical Evaluation of UDCA-Containing Oral Formulation in Mice for the Treatment of Wet Age-Related Macular Degeneration |
| title_sort | preclinical evaluation of udca containing oral formulation in mice for the treatment of wet age related macular degeneration |
| topic | ocular treatment ursodeoxycholic acid tauroursodeoxycholic acid bile acid age-related macular degeneration choroidal neovascularization |
| url | https://www.mdpi.com/1999-4923/11/11/561 |
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