Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability

Abstract

The potential of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) to overcome the intestinal barrier that limits oral liraglutide delivery was evaluated. Liraglutide-loaded PLGA NPs were prepared by the double emulsion solvent evaporation method. In vitro release kinetics and enzymatic degradation studies were conducted, mimicking the gastrointestinal environment. The permeability of liraglutide solution, liraglutide-loaded PLGA NPs, and liraglutide in the presence of the absorption enhancer PN159 peptide was tested on the Caco-2 cell model. Liraglutide release from PLGA NPs showed a biphasic release pattern with a burst effect of less than 15%. The PLGA nanosystem protected the encapsulated liraglutide from the conditions simulating the gastric environment. The permeability of liraglutide encapsulated in PLGA NPs was 1.5-fold higher (24 × 10−6 cm/s) across Caco-2 cells as compared to liraglutide solution. PLGA NPs were as effective at elevating liraglutide penetration as the tight junction-opening PN159 peptide. No morphological changes were seen in the intercellular junctions of Caco-2 cells after treatment with liraglutide-PLGA NPs, confirming the lack of a paracellular component in the transport mechanism. PLGA NPs, by protecting liraglutide from enzyme degradation and enhancing its permeability across intestinal epithelium, hold great potential as carriers for oral GLP-1 analog delivery.

Formulation and In Vitro Comparison Study between Lipid-Based and Polymeric-Based Nanoparticles for Nose-to-Brain Delivery of a Model Drug for Alzheimer’s Disease

“…This could be due to the nanoscale size of the prepared nanosystems which have the best nasal permeation properties as previously reported by Gänger et al [22]. Moreover, the spherical and smooth surface of both NPs, as confirmed by SEM images, leads to the least friction with the membrane surface in comparison with the needle-shape particles [32]. Stabilizing these NPs using poloxamer, a permeation enhancer, further improve their permeation properties [33], by inhibiting the efflux pumps in addition to lowering the membrane fluidity when it is used in vivo [34].…”

“…Stabilizing these NPs using poloxamer, a permeation enhancer, further improve their permeation properties [33], by inhibiting the efflux pumps in addition to lowering the membrane fluidity when it is used in vivo [34]. Interestingly, SLNs showed superior permeability over PLGA NPs, which might be explained by the lipophilic properties of these lipid-based nanosystems [35], which exceed those of PLGA NPs [32].…”

<p>Oral Nano Drug Delivery Systems for the Treatment of Type 2 Diabetes Mellitus: An Available Administration Strategy for Antidiabetic Phytocompounds</p>

“…143 Furthermore, the PLGA matrix provided a barrier for phytocompounds to prevent them from enzymatic degradation in the GIT. 144 PLA-Based NPs, PCL-Based NPs, and PVA-Based NPs PLA is often used with PGA to form PLGA. It is formed by the condensation polymerization of lactic acid, which is produced by the fermentation of sugars from carbohydrate sources like sugarcane, corn, or tapioca.…”

“… 143 Furthermore, the PLGA matrix provided a barrier for phytocompounds to prevent them from enzymatic degradation in the GIT. 144 …”

Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery

“…Among the various technologies having been developed to overcome the obstacles limiting oral peptide delivery [9,10], the formation of hydrophobic ion pairs (HIPs) proved to be promising as this can increase the lipophilic character of hydrophilic peptide drugs and thus enhance their permeability of lipophilic membranes [11,12]. Because of a limited stability of HIPs in the GI tract, the incorporation of HIPs into lipophilic carrier systems is advantageous [13][14][15].…”