pH-Dependent Structural Modification of Dipalmitoylphosphatidylcholine Vesicle Membranes by a Degradable Poly(carboxylic acid) of Pharmacological Importance

Abstract

The real and potential applications of phospholipid and surfactant vesicles in areas such as drug delivery, solar energy conversion, and chemical reactivity control have been discussed by Fendler. Additional applications may be foreseen for vesicles which can be made to respond to environmental stimuli such as heat, light, or specific chemical substances. One might imagine, for example, the use of such sensitized vesicles for selective release of drugs in targets of local hyperthermia) or low ambient pH). We have recently demonstrated that multilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) are rendered sensitive to pH in the presence of synthetic poly(carboxylic acid)s related to poly(acrylic acid). In biomedical applications, however, the non-degradability of these poly(acrylic acid) derivatives may be a serious limitation. In this paper, we show that a similar pH-dependent modification of DPPC vesicle structure may be effected by poly(P-malic acid) (PMLA 100), a degradable poly(carboxylic acid). PMLA 100 has been recently introduced to tailor-made macromolecular prodrugs and microemulsion-like systems for solubilization of hydrophobic drugs in aqueous media).