Evidence for phospholipid bilayer formation in solid lipid nanoparticles formulated with phospholipid and triglyceride.

Solid lipid nanoparticles (SLN) are comprised of a high-melting point triglyceride (TG) core with a phospholipid (PL) coating. This study has investigated the possible formation of multiple PL bilayers on the TG core of SLN's as a function of increasing the PL:TG molar ratio. Trilaurin (TL) was used as the SLN core. Dipalmitoylphos-phatdylcholine (DPPC) or a mixture of DPPC and dimyristoylphosphatidylglycerol (DMPG) were used to produce neutral and negatively charged SLN's. The volume of aqueous phase associated with the PL was determined using calcein and 6-carboxyfluorescein (6-CF) as hydrophilic markers incorporated during the preparation of the SLN's. The diameter of the SLN's decreased as the molar ratio of PL to TL was increased, until a PL:TL ratio of 0.15 was reached. After this point the diameter was not affected by further increases in the molar ratio. The experimental amount of PL required to prepare SLN's was significantly higher than the theoretical amount required to form a single monolayer on the surface. The aqueous volume associated with the PL was increased with increasing PL:TL molar ratios. The results obtained suggest that the formation of multiple PL bilayers is probable in SLN's prepared with a high molar ratio of PL to TL. The volume of the aqueous phase between the PL-bilayers, estimated from the amount of the hydrosoluble markers trapped in this phase, provides an indication of the relative number of bilayers at different PL:TL ratios.