Lung Delivery of Anticancer Agents--HFA Metered Inhalers

Florida Agricultural And Mechanical Univ, Tallahassee FL

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Abstract

Currently, inhalation delivery is actively pursued to deliver various therapeutic agents with a view to improve the drug efficacy in the treatment of diseases like asthma, cystic fibrosis and emphysema. The hypothesis of this proposal is that novel anti-cancer drugs like gemcitabine, 9-nitrocamptothecin, and taxotere can be formulated into stable and efficacious propellant (HFA 134A) based metered dose inhaler (mdI) formulations. The long-term objective of this proposal is to study the effect of administration of novel anti-cancer drugs via HFA 134a based mdI as a feasible ways of selective delivery to lungs for the treatment of lung cancer. The specific aims designed to achieve this objective are a) to formulate the anti-cancer drugs in HFA 134A based mdI formulations by appropriate formulation techniques b) to evaluate the mdI formulations for their aerosol properties like medication delivery, mass median aerodynamic diameter (MMAD) and shelf-life stability c) to assess the efficacy of mdI formulations for their cytotoxicity in vitro against human lung cancer cell lines and in vivo against lung tumor xenografts in nude mice. The anti-cancer drugs will be formulated into mdI by employing HFA 134a in combination with various surfactants. Appropriate particle size reduction techniques like ball milling and cryomilling will be employed to reduce the particle size of the drugs so as to prepare stale aerosol formulations. The MMAD of aerosols will be determined by Anderson cascade impactor. The physical and chemical stability of formulations will be extensively studied. The formulations will be further evaluated for their anti-cancer activity in vitro against human lung adenocarcinomas. Like A549 and NCI460 using six-stage viable cascade impactor. Formulations, which show promise in the stability studies and in vitro cytotoxicity studies, will be evaluated in vivo in human lung adenocarcinoma xenografts transplanted subcutaneously in the upper half of the dorsal thorax region in the swiss nu/nu nude mice. The results from this research will allow us to determine the efficacy of aerosolized delivery of anti-cancer agents by mdI for the treatment of lung cancer.