Particle engineering to enhance or lessen particle uptake by alveolar macrophages and to influence the therapeutic outcome

Abstract

The alveolar macrophages defend the lung against airborne pollutants and infectious microorganisms. Recent advances in the understanding of the role of macrophages in generation of immunological and inflammatory responses have established that alveolar macrophages could be used as targets for drug delivery. Enhanced uptake of particulate drug carriers by macrophages could be beneficial in pathological conditions such as tuberculosis and HIV where infectious microorganisms utilize macrophages as a safe haven and a vehicle to further infections. In contrary, to achieve prolonged residence time, extended drug release and in desired situations, increased systemic absorption, drug carrying particles that can avoid recognition and uptake by alveolar macrophages may prove to be significantly advantageous. Drug targeting to macrophages can achieve superior therapeutic efficacy for the treatment of medical conditions that involve tumorigenesis, inflammation and infections. Various particulate carriers containing therapeutic agents have been used to deliver drugs to the macrophages residing in the lung. Particulate systems have also been engineered to facilitate or avoid uptake by macrophages. But pathological conditions to be treated and drug delivery goals dictate the engineering approach for reducing or enhancing uptake by macrophages. In this review, we have summarized the influence of various physicochemical properties--composition, size, shape, pegylation and presence or absence of surface ligands--of particulate carriers on their uptake by macrophages. We have also described the macrophage biology and strategies that have been used to influence uptake and avoidance of particulate carriers by macrophages.

Keywords: Alveolar macrophages; Inhalation; Macrophage uptake; Particle engineering; Particulate carriers; Phagocytosis.