Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.
Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations.
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
Yue
Y
Yang
Wean Sin
WS
Cheow
Kunn
K
Hadinoto
D000327:Adsorption; D000336:Aerosols; D048271:Chitosan / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry* / Q000302:isolation & purification; D053761:Nanocomposites; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011122:Polyphosphates / Q000737:chemistry; D013025:Glycine max / Q000737:chemistry; D055672:Static Electricity; D013678:Technology, Pharmaceutical / Q000379:methods
D000336:Aerosols; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005079:Excipients; D054709:Lecithins; D011122:Polyphosphates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D016264:Dextran Sulfate; C005692:triphosphoric acid