Chitosan/heparin polyelectrolyte complexes as ion-paring approach to encapsulate heparin in orally administrable SLN: In vitro evaluation

Enhancing oral bioavailability of hydrophilic drugs by encapsulation in lipid-based nanocarriers, including Solid Lipid Nanoparticles (SLN), has been well documented. In this work, high molecular weight heparin was “insolubilized” an “ion-paring” approach, forming Chitosan/Heparin Polyelectrolyte Complexes (PEC) to promote its SLN. Hybrid PEC-SLN, heparin-loaded SLN (H-SLN) as naked PEC were prepared and characterized regarding size, Z potential, morphology, drug loading release. Physicochemical characterization the nanoparticles also performed differential scanning calorimetry (DSC), Fourier Transform Infra-Red (FTIR) analysis. FITC-labeled along with Nile Red labeled PEC-SLN assessed on CaCo-2 cells study cytotoxicity cell internalization ability cytometric confocal Transepithelial electrical resistance (TEER) measured NCM460 monolayers evaluate whether chitosan may induce a modification tight junctions’ integrity at epithelial level. Results showed that minimum size (around 170 nm) pH 5.5 positive surface charge after produced hybrid about 370 nm negative zeta potential. comparison both H-SLN PEC, able achieve pH-controlled release low toxicity rapid internalization. Finally, TEER measurements highlighted nanocarriers internalized without interference membrane resistance. Therefore, could be considered valuable candidate for further vivo investigations systemic heparin.