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Tailored design of pH-responsive microbeads for oral delivery of lactoferrin nanotherapeutics of colon cancer
Colorectal cancer, one of the most fatal cancer types, has an unmet need for the development of targeted oral therapeutics. To address this, we propose to engineer a multiparticulate system to enhance the efficacy of anticancer drugs for treatment of colon cancer. We have developed a dual ligand- an...
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Published in: | Journal of drug delivery science and technology 2024-08, Vol.97, p.105791, Article 105791 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | Colorectal cancer, one of the most fatal cancer types, has an unmet need for the development of targeted oral therapeutics. To address this, we propose to engineer a multiparticulate system to enhance the efficacy of anticancer drugs for treatment of colon cancer. We have developed a dual ligand- and pH-responsive multiparticulate system for oral drug delivery to the colon. Indomethacin (IND) and quercetin (QCT) preformulated as nanosuspensions (NSps) or liquid crystalline nanoparticles (LCNPs), respectively, were co-encapsulated into pH-responsive CA/HEC-MBs microbeads via ionoptropic gelation. To enhance tumor targeting, both nanoparticles were further coated with lactoferrin (Lf), which allows binding with Lf receptors on cancerous HCT-116 cells, resulting in higher internalization and superior cytotoxicity. Among various simulated gastrointestinal fluids, the engineered CA/HEC-MBs incorporating nanoparticles successfully released the drugs only in the colon (pH 6.8). Oral administration of both LF-targeted nanostructured microbeads into DMH-induced colorectal cancer bearing mice revealed superior in vivo anti-tumor efficacy. The microbeads efficiently reduced CEA and PCNA protein levels as well as the serum levels of IL-6, IL-1, and TNF-α. Apoptosis was also upregulated, as evidenced by increased Bax/Bcl2 ratio and increased expression levels of activated caspase-3 and caspase-9. Overall, these findings suggest that orally administered LF-targeted nanoparticle-based MBs for co-delivery of QCT and IND represent a promising alternative to conventional colon cancer therapy.
Calcium alginate/Hydroxy ethyl cellulose Microbeads (CA/HEC-MBs) for the co-delivery of Indomethacin (IND) and Quercetin (QCT) was developed for oral colon cancer targeted delivery. The drugs were preformulated as nanosuspensions (NSps) or liquid crystalline nanoparticles (LCNPs) and coated with Lactoferrin (Lf) prior to encapsulation in the MBs to bind with Lf receptors on cancer cells. CA/HEC-MBs treated groups manifested downregulation in CEA level, suppression of anti-apoptotic BCL-2 and activation of BAX and Caspase leading to tumor apoptosis. [Display omitted] |
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ISSN: | 1773-2247 |
DOI: | 10.1016/j.jddst.2024.105791 |