Development of enteric-coated, biphasic chitosan/HPMC microcapsules for colon-targeted delivery of anticancer drug-loaded nanoparticles
| Autor: | Allan G.A. Coombes, Yiming Ma, Kristofer J. Thurecht |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Drug
Curcumin Colon Colorectal cancer media_common.quotation_subject Pharmaceutical Science Nanoparticle Antineoplastic Agents Capsules Pharmacology Eudragit RS Chitosan chemistry.chemical_compound Drug Delivery Systems medicine Humans Enteric coated media_common Drug Carriers Chemistry technology industry and agriculture medicine.disease Anticancer drug Nanoparticles |
| Zdroj: | International Journal of Pharmaceutics. 607:121026 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2021.121026 |
| Popis: | Oral delivery of anticancer drug-loaded nanoparticles (NPs) to the colon offers opportunities to improve colorectal cancer (CRC) treatment by increasing the free drug concentration at tumour sites and/or enhancing NP accumulation in tumours. Indomethacin, 5-FU and curcumin, were entrapped separately in Eudragit RS NPs (approximately 10% w/w loading) using nanoprecipitation and incorporated in biphasic chitosan/HPMC microcapsules (MCs) using aerosolisation. The MCs were designed to release NPs primarily in the colon following chitosan breakdown by bacterial enzymes. Around 10% of the drug-loaded NPs was released from MCs in simulated intestinal fluid (SIF) in 6 h and 20% in simulated colon fluid (SCF). Indomethacin release from MCs was absent in simulated gastric fluid (SGF) and restricted to around 10% in SIF and SCF, respectively, demonstrating potential for delivering a large fraction of contained drug to the colon. Curcumin release from NPs or NP-loaded MCs was negligible in SGF, SIF and SCF, revealing opportunities for delivery of curcumin-loaded NPs to the colon for accumulation in tumours. Curcumin-loaded NPs reduced proliferation of human colon adenocarcinoma HT-29 cells by 83% compared with 50% for free curcumin. These findings demonstrate the potential of chitosan/HPMC microcapsules as a colon-specific delivery vehicle for oral nanomedicines directed against colorectal cancer. |
| Databáze: | OpenAIRE |
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