Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the branched polyesters, DEAPA-PVAL-g-PLGA.
OBJECTIVE
This study describes the development of surfactant-free, biodegradable nanoparticle systems with varying physicochemical properties and their suitability for pulmonary application via nebulization.


METHODS
Nanoparticle suspensions were formulated from the branched polyester, diethylaminopropyl amine-poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide) (DEAPA-PVAL-g-PLGA) alone, as well as with increasing amounts of carboxymethyl cellulose (CMC). Particle size, zeta potential, turbidity, and morphology (atomic force microscopy) were characterized. Three formulations were chosen for further study: Cationic nanoparticles without CMC, cationic nanoparticles with CMC, and anionic nanoparticles with an excess of CMC. Nanoparticle degradation was characterized, as well as stability during nebulization. Nanoparticle-cell interactions were investigated and quantified using confocal laser scanning microscopy and fluorescence spectrometry.


RESULTS
Nanoparticles ranged in size from 70-250 nm and displayed zeta potentials of +58.9 to -46.6 mV. Anionic nanoparticles showed the highest stability during nebulization. The degradation rate of each nanoparticle formulation decreased with increasing amounts of CMC. Cell association was highest among cationic nanoparticles (57% and 30%, respectively), although these were not internalized. Despite a lower rate of cell association (3%), anionic nanoparticles were internalized by A549 cells.


CONCLUSIONS
Surfactant-free nanoparticles from DEAPA-PVAL-g-PLGA are versatile drug delivery systems; however, only the anionic formulations investigated were proven suitable for aerosol therapy.
Dailey
L A
LA
Department of Pharmaceutics and Biopharmacy, Philipps University, Ketzerbach 63, 35037 Marburg, Germany.
Kleemann
E
E
Wittmar
M
M
Gessler
T
T
Schmehl
T
T
Roberts
C
C
Seeger
W
W
Kissel
T
T
D000336:Aerosols; D001711:Biotransformation; D002266:Carboxymethylcellulose Sodium; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D008863:Microspheres; D009391:Nephelometry and Turbidimetry; D010316:Particle Size; D010592:Pharmaceutic Aids; D011091:Polyesters / Q000737:chemistry*; D011098:Polyglactin 910 / Q000031:analogs & derivatives / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013535:Suspensions
D000336:Aerosols; D010592:Pharmaceutic Aids; D011091:Polyesters; D011108:Polymers; D013535:Suspensions; C483759:diethylaminopropyl amine-poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; D011142:Polyvinyl Alcohol; D002266:Carboxymethylcellulose Sodium