Development of enteric-coated, biphasic chitosan/HPMC microcapsules for colon-targeted delivery of anticancer drug-loaded nanoparticles

• Published in: International journal of pharmaceutics 2021-09, Vol.607, p.121026-121026, Article 121026
• Main Authors: Ma, Yiming, Thurecht, Kristofer J., Coombes, Allan G.A.
• Format: Article
• Language: English
• Subjects: Chitosan; Colorectal cancer; Curcumin; Eudragit; Microcapsules; Nanoparticles
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121026

[Display omitted] 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.