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Purpose To design and stabilize Liraglutide loaded poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) proper for oral administration. Methods PLGA NPs were prepared by means of double emulsion solvent evaporation method and optimized by applying 7-factor 2-level Plackett-Burman screening design. Results Spherical shaped NPs with homogeneous distribution, 188.95 nm particle size and 51.81% encapsulation efficiency were obtained. Liraglutide was successfully entrapped in the NPs while maintaining its native amorphous nature, and its structural integrity as well. Conclusion Lira-PLGA NPs with the required Critical Quality Attributes (CQAs) were successfully designed by implementing a 7-factor 8-run Plackett Burman design into the extended Quality by Design (QbD) model, to elucidate the effect of formulation and process variables on the particle size, size-distribution, encapsulation efficiency and surface charge. As the developed nanoparticles maintained the native structure of the active pharmaceutical ingredient (API), they are promising compositions for the further development for the oral delivery of Lira. Graphical Abstract Electronic supplementary material The online version of this article (10.1007/s11095-019-2620-9) contains supplementary material, which is available to authorized users.

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.