Liposomes for Pulmonary Drug Delivery: The Role of Formulation and Inhalation Device Design.

Abstract

Liposomes are established drug carriers for inhalation owing to their safety and ability to provide controlled drug release in the lung. These carriers can entrap a wide range of therapeutic molecules for delivery in large volumes to the peripheral airways using medical nebulizers. Pressurized metered inhalers (pMDIs), soft mist inhalers (SMIs) and dry powder inhalers (DPIs) can deliver relatively small quantities of medication to the lung when compared to medical nebulizers which can deliver large volumes using simple liposome preparation techniques. Unfortunately, the shearing provided during nebulization to convert the aqueous liposome dispersions into "respirable" aerosol droplets may exert physical stress on liposome bilayers, causing losses of the originally entrapped drug. The development of successful liposome carriers for inhalation depends on two main factors which are formulation composition and nebulizer design, with the aim of reducing the detrimental effect of shearing on liposome stability and maximizing the deposition of vesicles in the 'deep lung'. A number of nebulizable liposome formulations have reached clinical trials. For example, Arikace® (liposomal amikacin) and Pulmaquin® (liposomal ciprofloxacin) are antibacterial formulations currently in advanced stages of development. In this review, the role of liposome formulation and inhalation device design on the suitability of liposomes for eliciting controlled drug release in the lung was evaluated. Moreover, the factors contributing to the success of Arikace® in clinical trials were appraised.