Triglyceride-filled albumin-based nanocapsules: A promising new system to avoid discarding poorly water-soluble drug candidates

Hester S.; B. Ferenz K.; Adick A.; Kakalias C.; Mulac D.; Azhdari S.; Langer K.

Abstract

Even though current drug discovery provides a variety of potential drug candidates, many of those substances are difficult to formulate due to their poor water-solubility. To overcome this obstacle a technological formulation is crucial. Albumin-based nanocarriers are a possible intravenous delivery system which is already approved and commercially available. However, no universal carrier for poorly water-soluble substances is found yet. In the present study, new preparation processes for nanocapsules consisting of a medium-chain triglyceride (MCT) core and a human serum albumin (HSA) shell were developed. The nanocarrier system exhibits desirable physicochemical properties with a hydrodynamic diameter of 150 nm and a polydispersity index of 0.1. Furthermore, the nanocapsules were stable towards the addition of electrolytes and also in basic to neutral pH range. The nanocapsules were storage stable for at least 7 months at 4 °C and could also be lyophilized to reach an even longer shelf life of at least 21 months. In addition, the nanocapsule system showed no cytotoxicity in cell culture. The developed system represents a suitable carrier for a variety of different poorly water-soluble drug substances (e.g., fenofibrate, naproxen, indomethacin) showing a high potential for a universal formulation platform for further lipophilic active pharmaceutical ingredients (APIs).