Design and Development of Novel Mitochondrial Targeted

Zupančič, Š., Kocbek, P., Zariwala, M., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K.M.G. and Somavarapu, S. 2014. Design and Development of Novel Mitochondrial Targeted. Molecular Pharmaceutics. 11 (7), pp. 2334-2345.

TitleDesign and Development of Novel Mitochondrial Targeted
AuthorsZupančič, Š., Kocbek, P., Zariwala, M., Renshaw, D., Gul, M.O., Elsaid, Z., Taylor, K.M.G. and Somavarapu, S.
Abstract

Curcumin has potent antioxidant and antiinflammatory
properties but poor absorption following oral
administration owing to its low aqueous solubility. Development of novel formulations to improve its in vivo efficacy is therefore challenging. In this study, formulation of curcuminloaded DQAsomes (vesicles formed from the amphiphile, dequalinium) for pulmonary delivery is presented for the first time. The vesicles demonstrated mean hydrodynamic diameters between 170 and 200 nm, with a ζ potential of approximately +50 mV, high drug loading (up to 61%) and encapsulation efficiency (90%), resulting in enhanced curcumin aqueous solubility. Curcumin encapsulation in DQAsomes in the amorphous state was confirmed by X-ray diffraction and differential scanning calorimetry analysis. The existence of hydrogen bonds and cation−π interaction between curcumin and vesicle building blocks, namely dequalinium molecules, were shown in lyophilized DQAsomes using FT-IR analysis. Encapsulation of curcumin in DQAsomes enhanced the antioxidant activity of curcumin
compared to free curcumin. DQAsome dispersion was successfully nebulized with the majority of the delivered dose deposited in the second stage of the twin-stage impinger. The vesicles showed potential for mitochondrial targeting. Curcumin-loaded DQAsomes thus represent a promising inhalation formulation with improved stability characteristics and mitochondrial targeting ability, indicating a novel approach for efficient curcumin delivery for effective treatment of acute lung injury and the rationale for future in vivo studies.

Keywordsacute lung injury
antioxidant
curcumin
DQAsomes
nebulization
JournalMolecular Pharmaceutics
Journal citation11 (7), pp. 2334-2345
ISSN1543-8384
Year2014
PublisherAmerican Chemical Society
Digital Object Identifier (DOI)doi:10.1021/mp500003q
Publication dates
Published22 May 2014

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