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Pulmonary delivery of encapsulated cholroquin phosphate using polyester polymer based microparticles for potential treatment of lung cancer

Research Authors
H M Tawfeek, F M D Ismail, G A Hutcheon, I Y Saleem
Research Department
Research Journal
Journal of Aerosol Medicine and Pulmonary Drug Delivery
Research Rank
1
Research Vol
24 (6)
Research Year
2011
Research Abstract

. Chloroquine a potent antimalarial also demonstrates potency against selected cancers. In this study, we demonstrate pulmonary delivery of encapsulated chloroquine phosphate (CQP) using three poly(glycerol adipate-co--pentadecalactone) microparticles, PGA-co-PDL, PEG1500-PGA-co-PDL and PEG4500-PGA-co-PDL, and its effects on lung cancer cell growth. Methods. Microparticles encapsulated with CQP were prepared using spray drying-double emulsion technique. Encapsulation efficiency, water content, density, morphology and in-vitro release (PBS, pH 7.4) was characterised. Furthermore, aerosolisation behaviour was performed using the next generation impactor at 60L/min via HandiHaler® containing 20mg powder in HPMC capsule (size 2). MTT assay quantified the effect of encapsulated CQP and carrier-free CQP on human lung cancer bronchial epithelial cell (NCI-H727) proliferation. Results: PGA-co-PDL (11.4KDa), PEG1500-PGA-co-PDL (12.4KDa) and PEG4500-PGA-co-PDL (13.6KDa) resulted in low encapsulation efficiency (13.11±1.23, 10.52±0.86, 9.25±1.02). Furthermore, a biphasic release profile was predominant for all formulations, with ~40-45% of payload released after 24h. The aerosolisation performance (%FPF) was significantly greater for PEG1500-PGA-co-PDL (13.05±0.46%) and PEG4500-PGA-co-PDL( 14.66±0.46%) compared to PGA-co-PDL (9.52±0.50%) microparticle carriers. The higher FPF achieved with PEG4500-PGA-co-PDL microparticles was due to the significantly lower water content and true density (0.76±0.12%, 0.98±0.07g/cm3) respectively, as opposed to PEG1500-PGA-co-PDL (1.04±0.25%, 1.17±0.12g/cm3) and PGA-co-PDL (1.73±0.84, 1.24±0.35g/cm3), indicating less aggregation and enhanced flow properties. Treatment, 240-0.25µM, using carrier-free CQP (61.71±9.25-9.78±2.59) and encapsulated CQP (PGA-co-PDL: 63.88±11.13-19.38±8.55, PEG1500-PGA-co-PDL: 56.73±9.41-26.75±13.58, PEG4500-PGA-co-PDL: 62.46±8.57-25.24±5.41) resulted in a decrease in cell viability. Conclusion: Results from this investigation indicate CQP encapsulated with in PGA-co-PDL and PEG-PGA-co-PDL microparticles show promise as a pulmonary delivery system for treatment of lung cancers.