NanoCipro encapsulation in monodisperse large porous PLGA microparticles

Abstract

Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (∼10-15 μm) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (∼1-5 μm). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed.

Fabrication of Janus particles composed of poly (lactic-co-glycolic) acid and hard fat using a solvent evaporation method

“…Microparticles have been widely used in pharmaceutical formulations including as carriers for oral (1)(2)(3)(4)(5) and pulmonary drug delivery (6) or injectable formulations for long-term drug release (7). Developing microparticles as oral drug carriers to improve drug absorption in the gastrointestinal (GI) tract is an attractive challenge in the pharmaceutical field and a current focus.…”

Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols

“…[9][10][11][12][13][14][15] Inhalation aerosols for the treatment of pulmonary diseases date back to ancient times 7,16 and many inhalation products exist, of which dry powder inhalers (DPIs) are the fastest-growing segment. DPI formulations offer many advantages, including storing the drug in a dry state, leading to long-term stability, 17 the ability to encapsulate various types of therapeutics, 18 and the ease of DPI implementation.…”

A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

“…Pseudomonas aeruginosa [140,153] Nano-ciprofloxacin formulations achieved sustained release of drug directly at the site of pulmonary infection and appropriate aerodynamic particle size to achieve deep lung access for the drug [140,165] Polyisobutyl cyanoacrylate…”