ELSEVIER Journal of Controlled Release 35 (1995) 41-48 journal of controlled release A comparative study on the pulmonary delivery of tobramycin encapsulated into liposomes and PLA microspheres following intravenous and endotracheal delivery E.A. Poyner, H.O. Alpar *, A.J. Almeida, M.D. Gamble, M.R.W. Brown Pharmaceutical Sciences Institute, Aston University, Aston Triangle, Birmingham, B4 7ET, UK Received 6 April 1994; accepted 16 January 1995 Abstract The use of carriers to deliver tritiated tobramycin via intravenous and endotracheal routes to the lungs was investigated. Pulmonary, renal and vascular distribution were monitored at 6 and 24 h. The results indicated a significant difference (p < 0.05) between free drug, which is rapidly disseminated to other organs, specifically kidney, and liposomal and microcapsular tobramycin which was primarily retained in the lungs. Renal drug levels of intravenously delivered microcapsular tobramycin were signifi- cantly higher than those produced by liposomal administration at 6 (p_<0.025) and 24 h (p < 0.05). Liposomes however, produced pulmonary levels three times higher than those of the free drug both at 6 (p < 0.025) and 24 h (p < 0.025). At 24 h renal drug levels following endotracheal delivery were lower for both encapsulated forms than for the free drug (p < 0.005). Conversely, pulmonary drug levels were higher following encapsulated drug administration compared to those following free drug delivery at 24 h (p _< 0.005). These results demonstrate that tobramycin can be retained in the lung by means of liposomal and microencapsulated delivery systems after endotracheal delivery. Keywords: Phosphatidylcholineliposome; PLA microcapsule;Tobramycin;Intravenous;Endotrachealdelivery 1. Introduction Mucoid strains of Pseudomonas aeruginosa can result in a chronic life-threatening infection in cystic fibrosis (CF) patients [ 1 ]. Antibiotic therapy using a combination of a/3-1actam antibiotic and an aminog- iycoside [ 2 ] can improve the clinical condition without reducing the invading bacterial population [3]. Tobra- mycin, often administered systemically in CF, has been shown to reduce the levels of several P. aeruginosa extracellular virulence factors, both in vitro [4,5] and in vivo in the rat lung model for chronic local P. aeru- * Corresponding author. 0168-3659/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDIOI 68-3659( 95 )00017-8 ginosa infection [ 6]. After parenteral delivery, its pen- etration to lung tissue is limited and induces nephrotoxicity. Systemic drug treatment of lung dis- ease conditions is frequently associated with significant toxicity [7-9], e.g., aminoglycosides are potentially ototoxic and nephrotoxic. Pulmonary targeting of drugs encapsulated within liposomes or microcapsules to the lung, either through the circulation [ 10] or by aero- solisation [ 11-13] may enhance antimicrobial treat- ment of lung infections while simultaneously improving the therapeutic index [ 8]. To date, the influ- ence of sustained release delivery systems on the pul- monary absorption of entrapped tobramycin has not been investigated.