With the increasingly widespread of central nervous system (CNS) disorders and the lack of sufficiently effective medication, meloxicam (MEL) has been reported as a possible medication for Alzheimer's disease (AD) management. Unfortunately, following the conventional application routes, the low brain bioavailability of MEL forms a significant limitation. The intranasal (IN) administration route is considered revolutionary for CNS medications delivery. The objective of the present study was to develop two types of nanocarriers, poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) and solid lipid nanoparticles (SLNs), for the IN delivery of MEL adapting the Quality by Design approach (QbD). Turning then to further enhance the optimized nanoformulation behavior by chitosan-coating. SLNs showed higher encapsulation efficacy (EE) and drug loading (DL) than PLGA NPs (87.26% (EE) and 2.67% (DL); 72.23% (EE) and 2.55% (DL), respectively. MEL encapsulated into the nanoformulations improved in-vitro release, mucoadhesion, and permeation behavior compared to the native drug with greater superiority of chitosan-coated SLNs (C-SLNs). In vitro-in vivo correlation (IVIVC) results estimated a significant in vivo brain distribution of the nanoformulations compared to native MEL with estimated greater potential in the C-SLNs. Hence, MEL encapsulation into C-SLNs towards IN route can be promising in enhancing its brain bioavailability.

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.

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