PMID- 32437160 OWN - NLM STAT- MEDLINE DCOM- 20211011 LR - 20211011 IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 18 IP - 2 DP - 2021 Feb 1 TI - Oral Delivery of beta-Lactoglobulin-Nanosphere-Encapsulated Resveratrol Alleviates Inflammation in Winnie Mice with Spontaneous Ulcerative Colitis. PG - 627-640 LID - 10.1021/acs.molpharmaceut.0c00048 [doi] AB - Resveratrol (RES) is a nutraceutical with promising anti-inflammatory properties for the treatment of inflammatory bowel diseases (IBD). However, the clinical effectiveness of resveratrol as an oral anti-inflammatory agent is hindered by its extremely poor solubility and poor stability. In this study, we encapsulated resveratrol in beta-lactoglobulin (BLG) nanospheres and systematically analyzed their formulation parameters in vitro followed by a thorough in vivo anti-inflammatory testing in a highly specialized spontaneous murine UC model (Winnie mice model). Complexation of resveratrol with BLG increased the aqueous solubility of resveratrol by approximately 1.7 times with 10% w/w loading. Additionally, the in vitro dissolution of resveratrol from the particles was found to be higher compared to resveratrol alone, resulting in >90% resveratrol dissolution in approximately 8 h. The anti-inflammatory activity of resveratrol was examined for the first time in Winnie mice, a mouse model that closely represents the clinical signs of IBD. At a 50 mg/kg oral dose for 2 weeks, BLG-RES significantly improved both % body weight and disease activity index (DAI), compared to free resveratrol in Winnie mice. Importantly, histological evaluations revealed a similar trend with striking improvement in the pathology of the colon via an increase in goblet cell numbers and recovery of colonic epithelium. BLG-RES significantly increased the expression level of cytokine interleukin-10 (Il10), which confirms the reduction in inflammation potentially because of the increased dissolution and stability of resveratrol by complexation with BLG. This comprehensive study demonstrates the effectiveness of biocompatible nanomaterials such as BLG in oral delivery of poorly soluble anti-inflammatory molecules such as resveratrol in the treatment of IBD. FAU - Pujara, Naisarg AU - Pujara N AD - School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia. FAU - Wong, Kuan Yau AU - Wong KY AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. FAU - Qu, Zhi AU - Qu Z AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. FAU - Wang, Ran AU - Wang R AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. FAU - Moniruzzaman, Md AU - Moniruzzaman M AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. FAU - Rewatkar, Prarthana AU - Rewatkar P AD - School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia. FAU - Kumeria, Tushar AU - Kumeria T AD - School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia. FAU - Ross, Benjamin P AU - Ross BP AUID- ORCID: 0000-0002-1899-8484 AD - School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia. FAU - McGuckin, Michael AU - McGuckin M AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. AD - Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria 3010, Australia. FAU - Popat, Amirali AU - Popat A AUID- ORCID: 0000-0001-5401-3446 AD - School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072, Australia. AD - Mucosal Diseases Group, Mater Research Institute, The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, Queensland 4102, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200622 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Drug Carriers) RN - 0 (Lactoglobulins) RN - Q369O8926L (Resveratrol) SB - IM MH - Administration, Oral MH - Animals MH - Anti-Inflammatory Agents/*administration & dosage/chemistry/pharmacokinetics MH - Colitis, Ulcerative/*drug therapy/immunology/pathology MH - Colon/drug effects/immunology/pathology MH - Disease Models, Animal MH - Drug Carriers/*chemistry MH - Drug Compounding/methods MH - Drug Liberation MH - Female MH - Humans MH - Intestinal Mucosa/drug effects/immunology/pathology MH - Lactoglobulins/chemistry MH - Male MH - Mice MH - Nanospheres/chemistry MH - Resveratrol/*administration & dosage/chemistry/pharmacokinetics MH - Solubility OTO - NOTNLM OT - colitis OT - nanoparticles OT - nutraceuticals OT - resveratrol OT - solubility OT - beta-lactoglobulin EDAT- 2020/05/22 06:00 MHDA- 2021/10/12 06:00 CRDT- 2020/05/22 06:00 PHST- 2020/05/22 06:00 [pubmed] PHST- 2021/10/12 06:00 [medline] PHST- 2020/05/22 06:00 [entrez] AID - 10.1021/acs.molpharmaceut.0c00048 [doi] PST - ppublish SO - Mol Pharm. 2021 Feb 1;18(2):627-640. doi: 10.1021/acs.molpharmaceut.0c00048. Epub 2020 Jun 22.