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A Novel Nanocapsule Delivery System to Overcome Intestinal Degradation and Drug Transport Limited Absorption of P-glycoprotein Substrate Drugs

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Abstract

Purpose

To design a double-coated nanoparticulate delivery system of tacrolimus capable of overcoming the P-glycoprotein pump and CYP3A barriers without affecting their physiological activities.

Materials and Methods

Tacrolimus loaded oil cores were first nanoencapsulated with two polymethacrylate polymers followed by the microencapsulation of these nanocapsules within hydroxypropylmethylcellulose using a spray drying technique. The Trojan effect of these double-coated nanocapsules was evaluated in Caco-2 monolayer by monitoring the tacrolimus uptake and measuring the transport of tacrolimus across the rat jejunum membrane.

Results

The formulation was shown to release nanocapsules rather than dissolved drug under sink conditions. The nanocapsules protected tacrolimus from degradation in the diluted intestinal fluids following 2 h incubation. The Caco-2 and intestinal segment uptake of tacrolimus from the novel delivery system with and without verapamil was significantly higher than the uptake of tacrolimus from the aqueous solution and emulsion. The blank drug delivery system did not inhibit the P-gp pump activity. The nanocapsules internalized rapidly in the enterocytes as confirmed by the histological results.

Conclusion

The overall results suggest that the novel nanodelivery system which does not alter the activity of the P-gp is a potential platform for intestinal transport of sensitive lipophilic molecules that are P-gp substrates.

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Acknowledgement

This work was supported in part by a grant from the Chief Scientist Office of the Ministry of Trade and Industry (NOFAR program), Jerusalem, Israel and from Nanolymf Ltd., Rosh Ha’ayin, Israel. Simon Benita is affiliated with the David R. Bloom Center for Pharmacy at the Hebrew University of Jerusalem.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, P. O. Box 12065, 91120, Jerusalem, Israel

    Taher Nassar, Alona Rom & Simon Benita

  2. Consultant in Toxicological Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Abraham Nyska

Authors
  1. Taher Nassar
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  2. Alona Rom
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  3. Abraham Nyska
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  4. Simon Benita
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Correspondence to Simon Benita.

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Nassar, T., Rom, A., Nyska, A. et al. A Novel Nanocapsule Delivery System to Overcome Intestinal Degradation and Drug Transport Limited Absorption of P-glycoprotein Substrate Drugs. Pharm Res 25, 2019–2029 (2008). https://doi.org/10.1007/s11095-008-9585-4

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  • DOI: https://doi.org/10.1007/s11095-008-9585-4

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