Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.
In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
Iman
I
Alfagih
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Nitesh
N
Kunda
Kayali Chair for Pharmaceutical Industries, Department of Pharmaceutics, King Saud University, Riyadh, Saudi Arabia.
Fares
F
Alanazi
Research and Innovation, University of Central Lancashire, Preston, UK.
Sarah R
SR
Dennison
UCL School of Pharmacy, London, UK.
Satyanarayana
S
Somavarapu
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Gillian A
GA
Hutcheon
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK. Electronic address: i.saleem@ljmu.ac.uk.
Imran Y
IY
Saleem
D000280:Administration, Inhalation; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism / Q000379:methods; D003713:Dendritic Cells / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008863:Microspheres; D053761:Nanocomposites / Q000008:administration & dosage* / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry; D013499:Surface Properties
D004337:Drug Carriers; D004655:Emulsions; D011091:Polyesters; D011108:Polymers; D011506:Proteins; C568823:poly(glycerol adipate-co-omega-pentadecalactone); D012710:Serum Albumin, Bovine
biodegradable polymers; nanoparticles; particle size; polymeric drug delivery systems; protein delivery and formulation; pulmonary delivery; spray-drying