Development of permeation enhancer-Co-loaded solid lipid nanoparticles for enhanced oral bioavailability of alendronate

Abstract

Alendronate, marketed under the brand name Fosamax®, is a bisphosphonate that has been actively used in the clinical setting for the treatment of bone disease. However, the low intestinal permeability and bioavailability of alendronate significantly limit its therapeutic effectiveness. We developed alendronate/permeation enhancer co-loaded solid lipid nanoparticles (SLNs) composed of Compritol® 888 ATO or Gelot™ 64, Span 20, and F108, and demonstrated that the SLN formulation improved drug intestinal permeability with an excellent Papp value. Salcaprozate sodium (SNAC) was selected as the permeation enhancer because it enhanced drug transport across Caco-2 cell monolayers. Through the X-ray diffraction and differential scanning calorimetry, it was confirmed that both drugs were encapsulated in SLNs. Moreover, the alendronate/SNAC co-loaded SLNs exhibited a sustained-release profile, offering the potential to extend the therapeutic effects and reduce the dosing frequency, which is crucial for long-term osteoporosis treatment. Subsequently, the freeze-drying process improved the storage stability of SLNs, increasing their commercialization potential. This study demonstrates how SLNs and permeability enhancers can be used to bypass the drawbacks of the drug with poor permeability. © 2025