Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10162290 | Journal of Pharmaceutical Sciences | 2014 | 11 Pages |
Abstract
This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cellâpenetrating and lungâhoming peptide, conjugated polyethylene glycol-distearoylâphosphoethanolamine micelles containing fasudil, an investigational antiâPAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotalineâinduced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14Â nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7âfold and extended the drug halfâlife by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3743-3753, 2014
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Nilesh Gupta, Hany M. Ibrahim, Fakhrul Ahsan,