Solid lipid nanoparticles as drug carriers .1. Incorporation and retention of the lipophilic prodrug 3'-azido-3'-deoxythymidine palmitate

Solid lipid nanoparticles (SLN) were prepared with trilaurin (TL) as the SLN solid core and dipalmitoylphosphatidylcholine (DPPC) or a mixture of DPPC and dimyristoylphosphatidylglycerol (DMPG) to produce neutral and negatively charged SLNs. The ester prodrug of 3'-azido-3'-deoxythimidine (Zidovudine(R), AZT) with palmitic acid, AZT palmitate (AZT-P), was synthesized and its incorporation and retention in SLNs determined. The incorporation of hydrophilic AZT in SLNs was minimal; however the incorporation of AZT-P increased with increasing phospholipid (PL) content and was independent of the amount of TL used. The incorporation of AZT-P was greater in negatively charged SLNs than in neutral SLNs. The in vitro release of AZT-P from different SLNs formulation was studied at 37 degrees C using a bulk-equilibrium reverse dialysis sac technique. Increased drug release was observed in SLNs formulated with PLs having a transition temperature below 37 degrees C. The results obtained indicate that the highly packed TL core of the SLN is not compatible with lipophilic molecules such as AZT-P. The incorporation and subsequent retention of AZT-P appears to be dependent on the PL coating on the SLNs surface and is independent of the TL solid core. (C) 1997 Elsevier Science B.V.