Understanding the role of colon-specific microparticles based on retrograded starch/pectin in the delivery of chitosan nanoparticles along the gastrointestinal tract

Author(s)

dos Santos, Aline Martins ^[1] ; Meneguin, Andreia Bagliotti ^[1] ; Akhter, Dewan Taslima ^{[2, 3]} ; Fletcher, Nicholas ^{[2, 3]} ; Houston, Zachary H. ^{[2, 3]} ; Bell, Craig ^{[2, 3]} ; Thurecht, Kristofer J. ^{[2, 3]} ; Gremia, Maria Palmira Daflon ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Queensland, Ctr Adv Imaging, Australian Inst Bioengn & Nanotechnol, ARC Ctr Excellence Convergent Bionano Sci & Techn, St Lucia, Qld 4072 - Australia

^[3] Univ Queensland, ARC Training Ctr Innovat Biomed Imaging Technol, St Lucia, Qld 4072 - Australia

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS; v. 158, p. 371-378, JAN 2021.
• Web of Science Citations: 2

Abstract

The encapsulation of nanoparticles within microparticles designed for specific delivery to the colon is a relevant strategy to avoid premature degradation or release of nanoparticles during their passage through the stomach and upper gastrointestinal tract (GIT), allowing the targeted delivery of chemotherapeutics to the colon after oral administration. Here, we designed an oral multiparticulate system to achieve targeted release in the colon. In this sense, chitosan nanoparticles (CS NPs) encapsulated with 5-fluorouracil (5-FU) and incorporated into retrograded starch and pectin (RS/P) microparticles were developed and their in vivo distribution along the mouse GIT after oral administration was monitored using multispectral optical imaging. In vitro release studies revealed that the encapsulation of CS NPs into RS/P microparticles promoted greater control of 5-FU release rates, with a significant reduction (53%) in acid media that might replicate that found in the stomach following oral administration. The evaluation of the in vivo biodistribution of the CS NPs in mice showed a faster clearance in the distribution pattern along the mouse GIT, i.e., a shorter transit time of CS NPs compared to CS NPs-loaded RS/P microparticles. Additionally, CS NPs alone showed non-specific absorption into the blood-stream with associated kidney accumulation, while for the CS NPs-loaded RS/P microparticles no significant accumulation was observed in blood or major clearance organs. This suggests the specific degradability of RS/P by the colon microbiota appears to have been decisive in the higher protection of the CS NPs along the GIT until release in the colon, preventing unwanted absorption into the bloodstream and major organs following oral administration. Our findings represent a proof of concept for the use of RS/P microparticles as potential carriers for delivering drug-loaded nanoparticles to the colon and this work will contribute to the development of oral-systems for colorectal cancer therapy. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/25846-0 - Evaluation of the potential for colon-specific delivery of 5-fluorouracil nanoparticles and 5-fluorouracil nanoparticles incorporated in resistant starch/pectin microparticles, using a model of in vivo biodistribution by small animal optical imaging
• Grantee: Aline Martins dos Santos
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/01464-9 - Multifunctionalized systems-based chitosan nanoparticles anchored with methotrexate and incorporated into resistant starch/pectin microparticles for colon-specific release of 5-fluourouracil
• Grantee: Aline Martins dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate