New polymeric carriers for controlled drug delivery following inhalation or injection

Abstract

Inhalation is gaining increasing acceptance as a convenient, reproducible, and non-invasive method of drug delivery to the lung tissue and/or the systemic circulation. However, sustained drug release following inhalation remains elusive, due in part to the lack of appropriate materials designed specifically for use in the lungs to control the release of bioactive compounds. To address this problem, we have synthesized a new family of ether-anhydride copolymers composed entirely of FDA-approved monomers, including polyethylene glycol (PEG). Sebacic acid, a hydrophobic monomer, was copolymerized with PEG in order to produce water-insoluble polymers capable of providing continuous drug release kinetics following immersion in an aqueous environment. Various amounts of PEG (5-50% by mass) were incorporated into the backbone of the new polymers to allow tuning of particle surface properties for potentially enhanced aerosolization efficiency and to decrease particle clearance rates by phagocytosis in the deep lung. The preparation of large porous particles with these new polymers was systematically approached, utilizing central composite design, to develop improved particle physical properties for deep lung delivery. Microparticles containing model drugs were made with sizes suitable for deposition in various regions of the lung following inhalation as a dry powder. Due to such properties as surface erosion (leading to continuous drug release profiles), erosion times ranging from hours to days (allowing control over drug delivery duration), and ability to incorporate up to 50% PEG in their backbone, these new systems may also find application as "stealth" carriers for therapeutic compounds following intravenous injection.