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Effect of PEGylation on spray dried PGA-co-PDL pulmonary carrier microparticles and in-vitro transport

مؤلف البحث
H M Tawfeek, S H Khidr, E M Samy, S M Ahmed, G A Hutcheon, I.saleem
مجلة البحث
Journal of Aerosol Medicine and Pulmonary Drug Delivery
تصنيف البحث
1
عدد البحث
24 (6)
سنة البحث
2011
المشارك في البحث
ملخص البحث

Summary: Background: The current study investigates the effect of incorporating polyethylene glycol (PEG) into the backbone of a biodegradable polyester polymer, poly(glycerol adipate-co--pentadecalactone), PGA-co-PDL, as carriers for pulmonary drug delivery. PEG could be used to engineer the particle surface to reduce particle–particle interactions, enhance the hydrophilic nature of the polymer and improve their aerodynamic properties. Methods: Microparticles encapsulated with fluorescein sodium (SF) were prepared by spray drying directly from double emulsion and characterised for their encapsulation efficiency, density, morphology and in-vitro release in phosphate buffer saline (pH 7.4). Aerosolisation behaviour was investigated by placing 20mg powder into HPMC capsule (size 2) and aerosolised via HandiHaler® using the next generation impactor at 60L/min. In addition the transport of encapsulated SF across bronchial epithelial (calu-3) cells was investigated. Results: PGA-co-PDL (12.2KDa) and PEG-PGA-co-PDL (19.9KDa) had similar low encapsulation efficiency (17.11±0.45% and 15.02±0.07%), and density (0.81±0.03g/cm3 and 0.86±0.16g/cm3) respectively. However, a biphasic release profile was predominant for both polymers, with PEG-PGA-co-PDL having an enhanced release profile, with ~80% of payload release after 24h compared to ~60% for PGA-co-PDL microparticles. The FPF and MMAD were similar for SF loaded microparticles and ranged from 42.92±1.39%, 3.53±0.91μm (PGA-co-PDL), 41.65±2.62%, 3.80±1.47μm (PEG-PGA-co-PDL). Furthermore, there was a 10-fold increase in encapsulated SF (PGA-co-PDL: 2.65±1.82x10-5cm/s; PEG-PGA-co-PDL: 3.58±2.12x10-5cm/s) permeability across calu-3 epithelial cells compared to non-encapsulated (4.90±9.53x10-6cm/s), indicating opening of tight junctions. Conculsion: PEG-PGA-co-PDL microparticles may be a promising carrier for pulmonary drug delivery due to its enhanced sustained drug release profile, inducing faster permeability with excellent aerosolisation behavior.