title: Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers.
abstract: Although few experimental studies have been handled so far to exploit the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the production of dry powders for antibiotic inhalation, there has been no comprehensive study on the role played by NP composition. In this work, we try to shed light on this aspect by designing and developing a pulmonary delivery system for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM). At nanosize level, helper hydrophilic polymers were used to impart the desired surface, bulk and release properties to PLGA NPs prepared by a modified emulsion-solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and chitosan (CS) are essential to optimise the size and modulate the surface properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows efficient Tb entrapment within NPs and its release up to one month. Optimized formulations display good in vitro antimicrobial activity against P. aeruginosa planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM with peculiar but promising flow and aerosolization properties, while preserving the peculiar NP features. Nonetheless, in vivo biodistribution studies showed that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were found in great amounts in the upper airways, lining lung epithelial surfaces. In conclusion, PLGA NP composition appears to play a crucial role in determining not only the technological features of NPs but, once processed in the form of NEM, also their in vitro/in vivo deposition pattern.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy. ungaro@unina.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.forename: Ivana
authors.initials: I
authors.lastname: d'Angelo
authors.forename: Ciro
authors.initials: C
authors.lastname: Coletta
authors.forename: Roberta
authors.initials: R
authors.lastname: d'Emmanuele di Villa Bianca
authors.forename: Raffaella
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Brunella
authors.initials: B
authors.lastname: Perfetto
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
authors.forename: Agnese
authors.initials: A
authors.lastname: Miro
authors.forename: Maria Immacolata
authors.initials: MI
authors.lastname: La Rotonda
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003890:Desiccation / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage / Q000493:pharmacokinetics; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid