Stability of a liposomal formulation containing lipoyl or dihydrolipoyl acylglycerides

The acylglycerides of lipoic and dihydrolipoic acids may serve as slow-release sources for cutaneous delivery of these antioxidants when formulated in a liposomal vehicle.

Testing was conducted to determine the storage stability of lipoyl glycerides in phospholipid-based liposomes.

Lipoyl glycerides prepared by transesterification of lipoic acid with high oleic sunflower oil were incorporated into unilamellar liposomes comprised of soy phosphatidylcholine (soyPC) or dioleoylphosphatidylcholine (DOPC).

Lipoyl glycerides were stable in soyPC at 4 °C (90% remaining after five weeks) and decayed with a half-life (t(½)) of 14 d at 40 °C. In contrast, lipoyl glycerides embedded in DOPC were completely stable for four weeks at 40 °C. Dihydrolipoyl glycerides in soyPC converted to lipoyl glycerides at 4 °C (t(½) = 14 d) over four weeks, and much more rapidly so at 40 °C (t(½) = 1 d). A hydroperoxide accumulation analysis indicated that lipoyl glycerides and dihydrolipoyl glycerides were modified or degraded while suppressing autoxidation of the polyunsaturated fatty acids present in soyPC. Dynamic light scattering measurements found that liposomes containing lipoyl glycerides or dihydrolipoyl glycerides did not undergo significant size changes for at least 48 d, indicating that inclusion of the lipoic acid derivatives did not induce vesicle aggregation.

Substitution of the soyPC with DOPC, which is not readily subject to autoxidation, provided a much more stable storage environment for lipoyl glycerides. These findings confirm the expectation that phospholipid liposomes need to be oxidatively stable vehicles for dermal delivery of lipoic acid derivatives.