Mariam Zewail , Haidy Abbas , Nesrine El Sayed , Nihal M. El Newehy , Heba Abd-El-Azim
{"title":"载硫酸软骨素包覆石榴脂质载体的纳米杂交热敏水凝胶经空心微针皮内递送用于有效治疗类风湿性关节炎","authors":"Mariam Zewail , Haidy Abbas , Nesrine El Sayed , Nihal M. El Newehy , Heba Abd-El-Azim","doi":"10.1016/j.jddst.2025.107234","DOIUrl":null,"url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a common inflammatory arthritis type that significantly affects physical functions, leading to restrictions in daily activities. The current study aims to develop an effective nano-based drug delivery system for RA management using pomegranate peel extract (POM). POM was encapsulated in nanostructured lipid carriers (NLCs), coated with chondroitin sulphate (CHS) to actively target CD44 receptors that are over expressed in rheumatic joints. The optimized NLCs were loaded into Pluronic F127 hydrogels to prepare thermosensitive nanohybrid hydrogels for intradermal administration via AdminPen™ MNs hollow microneedles (Ho-MNs). The UPLC-ESI-MS/MS analysis of POM identified 76 compounds, predominantly polyphenols, known for anti-inflammatory and antioxidant properties. NLCs were prepared using the melt emulsification method, showing particle sizes ranging from 64.7 ± 0.34 to 341 ± 2.5 nm, zeta potentials between −17 ± 1.34 mV and −30 ± 0.98 mV, and high entrapment efficiencies (96.34 ± 0.34–98.89 ± 0.12 %). Nanohybrid hydrogels extended the release period of POM from 6 days to 13 days and reduced burst effects. <em>Ex vivo</em> studies confirmed effective skin penetration by AdminPen™ MNs. <em>In vivo</em> studies in rats with AIA demonstrated that POM nanohybrid hydrogels significantly relieved joint swelling and reduced TNF-α, IL-1β, MDA, and MMP-3 levels, while increasing NRF2 level. Histopathological examination revealed that the nanohybrid hydrogel-treated group had normal joint and cartilage structure. This novel system offers a minimally invasive, sustained-release approach for RA treatment, enhancing bioavailability and the therapeutic efficacy of POM, thus providing a promising alternative to conventional therapies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"112 ","pages":"Article 107234"},"PeriodicalIF":4.9000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intradermal delivery of nanohybrid thermosensitive hydrogels loaded with chondroitin sulphate coated pomegranate lipid carriers via hollow microneedles for effective rheumatoid arthritis management\",\"authors\":\"Mariam Zewail , Haidy Abbas , Nesrine El Sayed , Nihal M. El Newehy , Heba Abd-El-Azim\",\"doi\":\"10.1016/j.jddst.2025.107234\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Rheumatoid Arthritis (RA) is a common inflammatory arthritis type that significantly affects physical functions, leading to restrictions in daily activities. The current study aims to develop an effective nano-based drug delivery system for RA management using pomegranate peel extract (POM). POM was encapsulated in nanostructured lipid carriers (NLCs), coated with chondroitin sulphate (CHS) to actively target CD44 receptors that are over expressed in rheumatic joints. The optimized NLCs were loaded into Pluronic F127 hydrogels to prepare thermosensitive nanohybrid hydrogels for intradermal administration via AdminPen™ MNs hollow microneedles (Ho-MNs). The UPLC-ESI-MS/MS analysis of POM identified 76 compounds, predominantly polyphenols, known for anti-inflammatory and antioxidant properties. NLCs were prepared using the melt emulsification method, showing particle sizes ranging from 64.7 ± 0.34 to 341 ± 2.5 nm, zeta potentials between −17 ± 1.34 mV and −30 ± 0.98 mV, and high entrapment efficiencies (96.34 ± 0.34–98.89 ± 0.12 %). Nanohybrid hydrogels extended the release period of POM from 6 days to 13 days and reduced burst effects. <em>Ex vivo</em> studies confirmed effective skin penetration by AdminPen™ MNs. <em>In vivo</em> studies in rats with AIA demonstrated that POM nanohybrid hydrogels significantly relieved joint swelling and reduced TNF-α, IL-1β, MDA, and MMP-3 levels, while increasing NRF2 level. Histopathological examination revealed that the nanohybrid hydrogel-treated group had normal joint and cartilage structure. This novel system offers a minimally invasive, sustained-release approach for RA treatment, enhancing bioavailability and the therapeutic efficacy of POM, thus providing a promising alternative to conventional therapies.</div></div>\",\"PeriodicalId\":15600,\"journal\":{\"name\":\"Journal of Drug Delivery Science and Technology\",\"volume\":\"112 \",\"pages\":\"Article 107234\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-06-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Drug Delivery Science and Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1773224725006379\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Delivery Science and Technology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1773224725006379","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Intradermal delivery of nanohybrid thermosensitive hydrogels loaded with chondroitin sulphate coated pomegranate lipid carriers via hollow microneedles for effective rheumatoid arthritis management
Rheumatoid Arthritis (RA) is a common inflammatory arthritis type that significantly affects physical functions, leading to restrictions in daily activities. The current study aims to develop an effective nano-based drug delivery system for RA management using pomegranate peel extract (POM). POM was encapsulated in nanostructured lipid carriers (NLCs), coated with chondroitin sulphate (CHS) to actively target CD44 receptors that are over expressed in rheumatic joints. The optimized NLCs were loaded into Pluronic F127 hydrogels to prepare thermosensitive nanohybrid hydrogels for intradermal administration via AdminPen™ MNs hollow microneedles (Ho-MNs). The UPLC-ESI-MS/MS analysis of POM identified 76 compounds, predominantly polyphenols, known for anti-inflammatory and antioxidant properties. NLCs were prepared using the melt emulsification method, showing particle sizes ranging from 64.7 ± 0.34 to 341 ± 2.5 nm, zeta potentials between −17 ± 1.34 mV and −30 ± 0.98 mV, and high entrapment efficiencies (96.34 ± 0.34–98.89 ± 0.12 %). Nanohybrid hydrogels extended the release period of POM from 6 days to 13 days and reduced burst effects. Ex vivo studies confirmed effective skin penetration by AdminPen™ MNs. In vivo studies in rats with AIA demonstrated that POM nanohybrid hydrogels significantly relieved joint swelling and reduced TNF-α, IL-1β, MDA, and MMP-3 levels, while increasing NRF2 level. Histopathological examination revealed that the nanohybrid hydrogel-treated group had normal joint and cartilage structure. This novel system offers a minimally invasive, sustained-release approach for RA treatment, enhancing bioavailability and the therapeutic efficacy of POM, thus providing a promising alternative to conventional therapies.
期刊介绍:
The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.