PLGA, chitosan or chitosan-coated PLGA microparticles for alveolar delivery? A comparative study of particle stability during nebulization.
Various types of rifampicin (RIF)-loaded microparticles were compared for their stability during nebulization. Poly(lactide-co-glycolide) (PLGA), chitosan (CHT) and PLGA/CHT microparticles (MPs) were prepared by emulsion or precipitation techniques. MPs ability to be nebulized (NE%) as well as stability during freeze-drying or/and nebulization (NEED%), were evaluated after RIF extraction from MPs and determination by light spectroscopy. MP mean diameters and zeta-potential values were measured by dynamic light scattering, morphology was assessed by SEM, cytotoxicity by MTT method and mucoadhesive properties by mucin association. In all cases, freeze-drying prior to nebulization did not affect EE%, NE or NEED%. In CHT, MPs RIF encapsulation efficiency (EE%) decreased with increasing CHT concentration (viscosity) and CHT-MP NEED% was higher when the polymer was crosslinked by glutaraldehyde. PLGA MPs, exhibited both higher RIF EE% and also higher nebulization ability and NEED%, compared to CHT ones, but also higher cytotoxicity. However, when the two polymers were combined in the PLGA/CHT MPs, EE%, NE% and NEED% increased with increasing MP CHT-content. PLGA/CHT MPs with 0.50% or 0.75% CHT exhibited highest EE% for RIF and also best nebulization ability and stability, compared to all other MP formulations studied. Additionally they had good mucoadhesive properties and comparably low cytotoxicity.
Manca
Maria-Letizia
ML
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26510, Greece.
Mourtas
Spyridon
S
Dracopoulos
Vassileios
V
Fadda
Anna Maria
AM
Antimisiaris
Sophia G
SG
D000268:Adhesiveness; D000280:Administration, Inhalation; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D048271:Chitosan / Q000494:pharmacology* / Q000633:toxicity; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D004355:Drug Stability; D004563:Electrochemistry; D004655:Emulsions; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology* / Q000633:toxicity; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D009077:Mucins / Q000737:chemistry; D009092:Mucous Membrane / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011100:Polyglycolic Acid / Q000494:pharmacology* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000494:pharmacology* / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles
D000904:Antibiotics, Antitubercular; D004655:Emulsions; D009077:Mucins; D011108:Polymers; D012997:Solvents; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; C022616:thiazolyl blue; D012293:Rifampin