Influence of lipid matrix composition on biopharmaceutical properties of lipid nanoparticles

Lipid nanoparticles (LN) were invented in the early 1990ties and can be exploited for oral and topical drug delivery to increase the bioavailability of lipophilic active compounds. The lipid matrix of the LN can be composed of solid lipids or of a mixture of liquid and solid lipids. The influence of the lipid matrix composition of LN on the dermal penetration efficacy is not known and was therefore investigated in this study. For this the whole spectrum of LN, that means NE (100% liquid lipid), SLN (100% solid lipid) and NLC that contained low, medium and high amounts of oil were produced and characterized in regard to size, zeta potential, crystallinity and in-vitro release. In addition, the dermal penetration efficacy was determined ex-vivo and the bio-physical skin parameters, i.e., spreadability on skin, skin hydration, skin friction and transepidermal water loss were also assessed. Results demonstrate the tremendous influence of the lipid matrix composition on the biopharmaceutical properties of the LN but showed only minor differences in the physico-chemical properties of the particles. The physico-chemical properties of the LN and the in-vitro release data were not clearly linked to the dermal penetration efficacy, because also other parameters, e.g., skin hydration, spreadability of the formulation on skin and/or film formation of the LN on skin were found to be important parameters that influence the dermal penetration efficacy. Therefore, to allow for the development of effective LN formulations with tailor-made biopharmaceutical properties, not only the physico-chemical properties and in-vitro drug release profiles but also the most relevant biopharmaceutical properties of the LN should be assessed during the formulation development of LN.