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Labrasol-Enriched Nanoliposomal Formulation: Novel Approach to Improve Oral Absorption of Water-Insoluble Drug, Carvedilol

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Abstract

The purpose of the current study was to develop a novel liposomal formulation to improve the oral bioavailability of carvedilol, a Biopharmaceutics Classification System class II with poor aqueous solubility and extensive presystemic metabolism. Conventional and various surfactant-enriched carvedilol-loaded liposomes were prepared by thin film hydration technique and physicochemical properties of liposomes (including size, encapsulation efficiency, release behavior, and morphology) were evaluated. To assess the oral bioavailability, in vivo studies were carried out in eight groups of male Wistar rats (n = 6) and the drug plasma concentration was determined. Conventional and surfactant containing liposomes showed average particle size of 76–104 nm with a narrow size distribution, high encapsulation efficiency (80%≤) and a sustained release profile in simulated intestinal fluid. Compared to the suspension, conventional and Labrasol containing liposomes significantly improved the oral bioavailability and peak plasma concentration of carvedilol. Biocompatibility studies (cell cytotoxicity and histopathological analyses) showed that the enhancing effect might be achieved without any apparent toxicity in the intestine. Decreased oral absorption of carvedilol nanovesicles by using a chylomicron flow blocker indicated contribution of lymphatic transport in nanocapsules absorption. The results reported the successful development of biocompatible Labrasol-enriched carvedilol nanoliposomal formulation with a significant oral enhancement capability.

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Funding

This study was supported by a grant from Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Samaneh Ghassemi, Azadeh Haeri & Simin Dadashzadeh

  2. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Soraya Shahhosseini

  3. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Simin Dadashzadeh

Authors
  1. Samaneh Ghassemi
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  2. Azadeh Haeri
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  3. Soraya Shahhosseini
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  4. Simin Dadashzadeh
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Correspondence to Azadeh Haeri or Simin Dadashzadeh.

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Ghassemi, S., Haeri, A., Shahhosseini, S. et al. Labrasol-Enriched Nanoliposomal Formulation: Novel Approach to Improve Oral Absorption of Water-Insoluble Drug, Carvedilol. AAPS PharmSciTech 19, 2961–2970 (2018). https://doi.org/10.1208/s12249-018-1118-9

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