Inhalable antibiotic delivery using a dry powder co-delivering recombinant deoxyribonuclease and ciprofloxacin for treatment of cystic fibrosis.
OBJECTIVE
To achieve efficient antibiotic delivery to the cystic fibrosis (CF) airway using a single inhalable powder co-encapsulating a mucolytic and an antibiotic.


METHODS
Inhalable dry powders containing deoxyribonuclease and/or ciprofloxacin (DNase, Cipro, and DNase/Cipro powders) were produced by spray-drying with dipalmitylphosphatidylcholine, albumin, and lactose as excipients, and their antibacterial effects were evaluated using the artificial sputum model.


RESULTS
All powders showed mass median aerodynamic diameters below 5 microm. Both drugs were loaded in the dry powders without loss in quantity and activity. Dry powders containing DNase significantly decreased the storage modulus of the artificial sputum medium in less than 30 min. When applied to artificial sputum laden with Pseudomonas aeruginosa, Cipro/DNase powder showed better antibacterial activity than Cipro powder. The higher activity of the Cipro/DNase powder is attributable to the mucolytic activity of DNase, which promotes penetration of the dry powder into the artificial sputum and efficient dissolution and diffusion of ciprofloxacin.


CONCLUSIONS
Inhalational delivery of antibiotics to the CF airway can be optimized when the sputum barrier is concomitantly addressed. Co-delivery of antibiotics and DNase using an inhalable particle system may be a promising strategy for local antipseudomonal therapy in the CF airway.
Yang
Yan
Y
School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
Tsifansky
Michael D
MD
Wu
Chia-Jung
CJ
Yang
Hae In
HI
Schmidt
Gudrun
G
Yeo
Yoon
Y
D000280:Administration, Inhalation; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000188:drug therapy; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage* / Q000494:pharmacology; D004339:Drug Compounding / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods*; D005100:Expectorants / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012212:Rheology; D013183:Sputum / Q000737:chemistry / Q000187:drug effects
D000890:Anti-Infective Agents; D004337:Drug Carriers; D005100:Expectorants; D011208:Powders; D002939:Ciprofloxacin; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I