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

Autor: Zachary H. Houston, Craig A. Bell, Aline Martins dos Santos, Maria Palmira Daflon Gremião, Nicholas L. Fletcher, Andréia Bagliotti Meneguin, Kristofer J. Thurecht, Dewan Taslima Akhter
Přispěvatelé: Universidade Estadual Paulista (Unesp), The University of Queensland
Rok vydání: 2020
Předmět:
Colorectal cancer
Pharmaceutical Science
Administration
Oral
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
Chitosan
chemistry.chemical_compound
Mice
Biodistribution
0302 clinical medicine
Oral administration
Tissue Distribution
Intestinal Mucosa
Gastrointestinal tract
Drug Carriers
Chemistry
Stomach
Starch
General Medicine
021001 nanoscience & nanotechnology
Pectin
medicine.anatomical_structure
Models
Animal
Pectins
Female
Fluorouracil
0210 nano-technology
Colorectal Neoplasms
Biotechnology
Colon
Drug Compounding
Biological Availability
Antineoplastic Agents
Microparticles
Proof of Concept Study
03 medical and health sciences
In vivo
Colon-specific delivery
medicine
Animals
Humans
Particle Size
medicine.disease
In vitro
Gastrointestinal Microbiome
Drug Liberation
Retrograded starch
Intestinal Absorption
Nanoparticles
Oral drug delivery
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1873-3441
Popis: Made available in DSpace on 2021-06-25T11:09:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. São Paulo State University (UNESP) School of Pharmaceutical Sciences Centre for Advanced Imaging Australian Institute for Bioengineering and Nanotechnology ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and ARC Training Centre for Innovation in Biomedical Imaging Technology The University of Queensland São Paulo State University (UNESP) School of Pharmaceutical Sciences CNPq: 465687/2014-8
Databáze: OpenAIRE
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