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A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism.
J Pharm Sci. 2014 Nov; 103(11):3491-3500.JP

Abstract

A mixed lipid-mixed surfactant self-microemulsifying drug delivery system (SMEDDS) was developed to exploit the health benefits of resveratrol, a Biopharmaceutical Classification System Class 2 natural polyphenol, subject to extensive intestinal presystemic metabolism. SMEDDS with a mixed lipid phase (castor oil/Capmul MCM 1:1) and a mixed surfactant phase (Kolliphor EL/Kolliphor RH 40 1:1) was developed and evaluated for its self-emulsifying properties and in vitro dispersion. The impact of SMEDDS on the permeability properties of resveratrol and its metabolite fluxes through the rat intestine and Caco-2 cells was monitored. The inhibitory effect of selected SMEDDS components on the efflux transporters multidrug resistance-associated protein and P-gp as well as cytotoxicity was assessed on Caco-2 cells. The formulation allowed for high resveratrol loading (122.5 mg/g SMEDDS), excellent self-emulsifying properties, and very rapid release. When formulated in SMEDDS, resveratrol metabolite efflux significantly declined. The formulation (SMEDDS without incorporated resveratrol) and its individual components did not compromise in vitro cell vitality and integrity. Mixed lipid-mixed surfactant SMEDDS is a prospective formulation to improve resveratrol biopharmaceutical, pharmacokinetic, and toxicological properties, leading the way to resveratrol use not only as a supplement but also as a pharmacological drug.

Authors+Show Affiliations

Faculty of Pharmacy, Chair of Pharmaceutical Technology, University of Ljubljana, Slovenia.Lek Pharmaceuticals d.d, Ljubljana, Slovenia.Faculty of Pharmacy, Chair of Biopharmaceutics and Pharmacokinetics, University of Ljubljana, Slovenia.Faculty of Pharmacy, Chair of Pharmaceutical Technology, University of Ljubljana, Slovenia.Faculty of Pharmacy, Chair of Biopharmaceutics and Pharmacokinetics, University of Ljubljana, Slovenia.Faculty of Pharmacy, Chair of Pharmaceutical Technology, University of Ljubljana, Slovenia. Electronic address: mirjana.gasperlin@ffa.uni-lj.si.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25103361

Citation

Seljak, Katarina Bolko, et al. "A Self-microemulsifying Drug Delivery System to Overcome Intestinal Resveratrol Toxicity and Presystemic Metabolism." Journal of Pharmaceutical Sciences, vol. 103, no. 11, 2014, pp. 3491-3500.
Seljak KB, Berginc K, Trontelj J, et al. A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism. J Pharm Sci. 2014;103(11):3491-3500.
Seljak, K. B., Berginc, K., Trontelj, J., Zvonar, A., Kristl, A., & Gašperlin, M. (2014). A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism. Journal of Pharmaceutical Sciences, 103(11), 3491-3500. https://doi.org/10.1002/jps.24114
Seljak KB, et al. A Self-microemulsifying Drug Delivery System to Overcome Intestinal Resveratrol Toxicity and Presystemic Metabolism. J Pharm Sci. 2014;103(11):3491-3500. PubMed PMID: 25103361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism. AU - Seljak,Katarina Bolko, AU - Berginc,Katja, AU - Trontelj,Jurij, AU - Zvonar,Alenka, AU - Kristl,Albin, AU - Gašperlin,Mirjana, Y1 - 2014/08/07/ PY - 2014/05/12/received PY - 2014/07/09/revised PY - 2014/07/16/accepted PY - 2014/8/9/entrez PY - 2014/8/12/pubmed PY - 2015/6/27/medline KW - Caco-2 cells KW - dissolution KW - drug delivery systems KW - gastrointestinal KW - lipids KW - phase diagram KW - self-emulsifying KW - solubility KW - surfactants SP - 3491 EP - 3500 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 103 IS - 11 N2 - A mixed lipid-mixed surfactant self-microemulsifying drug delivery system (SMEDDS) was developed to exploit the health benefits of resveratrol, a Biopharmaceutical Classification System Class 2 natural polyphenol, subject to extensive intestinal presystemic metabolism. SMEDDS with a mixed lipid phase (castor oil/Capmul MCM 1:1) and a mixed surfactant phase (Kolliphor EL/Kolliphor RH 40 1:1) was developed and evaluated for its self-emulsifying properties and in vitro dispersion. The impact of SMEDDS on the permeability properties of resveratrol and its metabolite fluxes through the rat intestine and Caco-2 cells was monitored. The inhibitory effect of selected SMEDDS components on the efflux transporters multidrug resistance-associated protein and P-gp as well as cytotoxicity was assessed on Caco-2 cells. The formulation allowed for high resveratrol loading (122.5 mg/g SMEDDS), excellent self-emulsifying properties, and very rapid release. When formulated in SMEDDS, resveratrol metabolite efflux significantly declined. The formulation (SMEDDS without incorporated resveratrol) and its individual components did not compromise in vitro cell vitality and integrity. Mixed lipid-mixed surfactant SMEDDS is a prospective formulation to improve resveratrol biopharmaceutical, pharmacokinetic, and toxicological properties, leading the way to resveratrol use not only as a supplement but also as a pharmacological drug. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/25103361/A_self_microemulsifying_drug_delivery_system_to_overcome_intestinal_resveratrol_toxicity_and_presystemic_metabolism_ DB - PRIME DP - Unbound Medicine ER -