Safety and efficacy studies of liposomes in specific immunotherapy

Abstract

Liposomes are lipid vesicles that have been extensively investigated because of their immunoadjuvant properties and their capacity to transport a variety of therapeutic agents. This article reports the results of 4 safety and efficacy studies of multilamellar liposomes used to incorporate an allergen extract in specific immunotherapy. The first study showed that cutaneous tolerance of encapsulated allergen extracts (5 grass pollens or Dermatophagoides pteronyssinus [house dust mites]) administered in the form of prick tests or intradermal reactions was significantly better than that of the same extract in aqueous form. The local and systemic safety of empty liposomes administered by subcutaneous injection at various concentrations was assessed in a double-masked, placebo-controlled study (study 2) in 24 healthy subjects: 2 subjects receiving the lowest dose developed delayed hypersensitivity reactions to alphatocopherol (used as an antioxidant in the liposome preparation) that required discontinuation of treatment. Apart from these 2 subjects, the 3 concentrations of empty liposomes were well tolerated locally and systemically. In a third study, the safety of encapsulated allergen extracts (5 grass pollens or D pteronyssinus) administered subcutaneously was found to be relatively good, similar to that of conventional immunotherapy. Using an index of reactivity (IR) as the unit of measure, the 50-IR/mL concentration was poorly tolerated, with 72% immediate local reactions, 39% delayed local reactions, and 16% systemic reactions for a volume of 0.20 mL. Finally, in study 4, the safety and efficacy of liposomal allergen extracts were assessed in a clinical trial of specific immunotherapy to 5 grass pollens versus placebo and versus an identical extract adsorbed onto calcium phosphate. The 10-IR/mL liposomal extract was slightly more effective than the extract adsorbed onto calcium phosphate in terms of clinical response and specific reactivity (nasal, conjunctival, and cutaneous). However, the systemic safety of encapsulated extracts was less favorable than that of the adsorbed extract. Because of this finding and the delayed local reactions observed with empty liposomes, it appears that liposomal allergen is not a suitable formulation, especially since the manufacturing process is complex.