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Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery

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ABSTRACT

Purpose

The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery.

Methods

Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers (L-arginine and L-leucine) (0.5–1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug.

Results

Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, L-leucine was significantly superior in enhancing the aerosolization performance (L-arginine:%FPF 27.61 ± 4.49–26.57 ± 1.85; FPD 12.40 ± 0.99–19.54 ± 0.16 μg and MMAD 2.18 ± 0.35–2.98 ± 0.25 μm, L-leucine:%FPF 36.90 ± 3.6–43.38 ± 5.6; FPD 18.66 ± 2.90–21.58 ± 2.46 μg and MMAD 2.55 ± 0.03–3.68 ± 0.12 μm). Incorporating L-leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi’s pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment.

Conclusion

The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.

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ACKNOWLEDGMENTS

Hesham Tawfeek would like to thank the Ministry of Higher Education, Egyptian government, for funding his Ph.D studies at Liverpool John Moores University.

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Authors and Affiliations

  1. School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool, L3 3AF, UK

    Hesham Tawfeek, Mark Murphy, Gillian Hutcheon & Imran Saleem

  2. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt

    Hesham Tawfeek, Sayed Khidr, Eman Samy & Sayed Ahmed

  3. General Engineering Research Institute, Liverpool John Moores University, Liverpool, UK

    Mark Murphy

  4. Aston Pharmacy School, Aston University, Birmingham, UK

    Afzaal Mohammed & Anjum Shabir

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  1. Hesham Tawfeek
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Correspondence to Imran Saleem.

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Tawfeek, H., Khidr, S., Samy, E. et al. Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery. Pharm Res 28, 2086–2097 (2011). https://doi.org/10.1007/s11095-011-0433-6

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