Liraglutide Solution

Intestinal L cells are an important subtype of intestinal epithelial endocrine cells, mainly distributed in the ileum, distal colon, and lower jejunum, scattered along the axis of intestinal villous crypts, accounting for 0.5% to 1% of the total number of intestinal epithelial cells.
Molecular phenotype: High expression of GLP-1 receptor (GLP-1 R), G protein coupled receptor 120 (GPR120), bile acid receptor (FXR/TGR5), sodium dependent bile acid transporter (ASBT), NPC1L1 cholesterol transporter, providing specific targets for targeted delivery of liraglutide.

Traditional GLP-1RA only activates receptors through exogenous drugs, while L cell targeted delivery can achieve:
Direct effect: Liraglutide binds to GLP-1R on the surface of L cells, activating the intracellular cAMP/PKA pathway, promoting insulin secretion, and inhibiting glucagon.
Indirect effect: Activation of L cells promotes the release of endogenous GLP-1 and PYY, forming a "drug cell endogenous hormone" amplification effect, which increases the hypoglycemic and weight loss effects by 40% to 60%.
Synergistic effect: Exogenous liraglutide has a half-life of 13 hours, while endogenous GLP-1 rapidly secretes, achieving a dual effect of rapid onset and long-term maintenance.

The Liraglutide solution L cell targeted delivery platform focuses on precise targeting, efficient penetration, stable protection, and controlled release, constructing an integrated system of "L cell homing+mucosal penetration+enzymatic protection+sequential release".
Targeted homing: Surface coupled with L cell specific ligands (bile acids, fatty acids, GPR120 agonists) to achieve L cell surface enrichment.
Mucosal penetration: Adding penetration enhancers (bile salts, rhamnolipids, chitosan) to open the mucosal network and promote cross cell/paracellular transport.
Enzymatic protection: Encapsulated with nano micelles, liposomes, and protein complexes to isolate proteases, the stability is increased by 10-20 times.
Controlled release: pH sensitive/enzyme sensitive carrier, precise drug release in ileal pH 6.5-7.5 environment, matching the peak distribution of L cells.

Lipid Nanovesicle Solution (LIRA-LN)
Construction: DSPE-PEG2000, soybean phospholipids, and cholesterol form lipid vesicles, encapsulating liraglutide with a particle size of 80-150 nm.
Targeting mechanism: PEGylation reduces clearance, surface modification of C16 fatty acids (intrinsic side chains of liraglutide), targeting L cells GPR120 and GLP-1R.
Advantages: High biocompatibility, encapsulation efficiency of 75%~85%, and intestinal retention time>24 hours.

Protein Corona Liposome Solution (Pc AT LIRA)
Construction: Cationic liposomes encapsulating liraglutide, surface adsorbed BSA protein crown, connected to AT-1002 penetration enhancer.
Targeting mechanism: Protein crown reduces immune clearance, AT-1002 opens tight junctions, and L cell targeting efficiency is doubled.
Advantages: Good stability, cross mucosal transport rate of 45%, suitable for long-term oral administration.

Hypoglycemic effect (db/db mice, orally administered for 4 weeks)
Free Liraglutide: reduces fasting blood glucose by 12% to 15% and HbA1c by 0.5% to 0.8%, with minimal effect.
LIRA/CA solution: Fasting blood glucose decreased by 42% to 48%, HbA1c decreased by 2.1% to 2.5%, equivalent to subcutaneous injection (1.8mg).
LIRA-LN solution: Fasting blood glucose is reduced by 45%~52%, HbA1c is reduced by 2.3%~2.8%, and the therapeutic effect is better than subcutaneous injection.