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A Microgel Platform Enables Site-Specific Intestinal Delivery of Lactoferrin, Improving its Bioavailability for
Huiling Yan1,2, Yixuan Li1, Shanan Chen1,2
1Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
Summary
Novel microgels made from plant polysaccharides deliver lactoferrin (Lf) to specific gut sites. This targeted delivery enhances Lf bioavailability and treats liver injury or colitis effectively.
Area of Science:
- Biomaterials Science
- Drug Delivery
- Gastroenterology
Background:
- Oral delivery of bioactive proteins faces challenges in gastric protection and targeted intestinal release.
- Lactoferrin (Lf) has therapeutic potential but requires effective delivery systems.
- Artemisia sphaerocephala Krasch. polysaccharides (ASKP) are eco-friendly and biocompatible materials.
Purpose of the Study:
- To design and evaluate two types of intestinal site-specific microgels for lactoferrin (Lf) delivery.
- To achieve on-demand release of Lf in either the small intestine or colon.
- To demonstrate the therapeutic efficacy of targeted Lf delivery in preclinical models.
Main Methods:
- Developed two microgel formulations using ASKP with different cross-linking strategies (Fe3+-COO- or STMP).
- Evaluated microgel stability in gastric conditions and Lf release profiles in vitro.
- Assessed Lf bioavailability, hepatic accumulation, and therapeutic effects in models of alcoholic liver injury and ulcerative colitis.
- Investigated the underlying molecular mechanisms, including antioxidant pathways and inflammatory signaling.
Main Results:
- Both microgels successfully protected Lf from digestion and facilitated receptor-mediated endocytosis.
- Small intestine-targeted microgels increased Lf bioavailability by approximately 6-fold, leading to hepatic Lf accumulation and amelioration of alcoholic liver injury via Nrf2 and CPT1A pathways.
- Colon-targeted microgels alleviated ulcerative colitis by suppressing the TLR4/MyD88/NF-κB pathway and restoring gut microbiota.
Conclusions:
- This study presents the first use of distinct cross-linking chemistries on the same ASKP backbone for site-specific intestinal delivery.
- The developed food-grade microgel platforms enable spatiotemporally controlled, on-demand delivery of bioactive proteins for distinct therapeutic actions in different gut regions.
- These microgels represent a promising platform for oral protein therapeutics, addressing key delivery challenges.
