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Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.
Int J Pharm. 2014 Jan 02; 460(1-2):131-43.IJ

Abstract

Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug.

Authors+Show Affiliations

Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.Division of Biology, TCG Life Sciences Ltd., Kolkata, India.School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India. Electronic address: proftkpal@gmail.com.

Pub Type(s)

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

Language

eng

PubMed ID

24239580

Citation

Choudhury, Hira, et al. "Improvement of Cellular Uptake, in Vitro Antitumor Activity and Sustained Release Profile With Increased Bioavailability From a Nanoemulsion Platform." International Journal of Pharmaceutics, vol. 460, no. 1-2, 2014, pp. 131-43.
Choudhury H, Gorain B, Karmakar S, et al. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. Int J Pharm. 2014;460(1-2):131-43.
Choudhury, H., Gorain, B., Karmakar, S., Biswas, E., Dey, G., Barik, R., Mandal, M., & Pal, T. K. (2014). Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. International Journal of Pharmaceutics, 460(1-2), 131-43. https://doi.org/10.1016/j.ijpharm.2013.10.055
Choudhury H, et al. Improvement of Cellular Uptake, in Vitro Antitumor Activity and Sustained Release Profile With Increased Bioavailability From a Nanoemulsion Platform. Int J Pharm. 2014 Jan 2;460(1-2):131-43. PubMed PMID: 24239580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. AU - Choudhury,Hira, AU - Gorain,Bapi, AU - Karmakar,Sanmoy, AU - Biswas,Easha, AU - Dey,Goutam, AU - Barik,Rajib, AU - Mandal,Mahitosh, AU - Pal,Tapan Kumar, Y1 - 2013/11/13/ PY - 2013/08/02/received PY - 2013/10/25/revised PY - 2013/10/28/accepted PY - 2013/11/19/entrez PY - 2013/11/19/pubmed PY - 2014/9/10/medline KW - Breast cancer cell line KW - Caco-2 permeability KW - Nanoemulsion KW - Oral bioavailability KW - Paclitaxel KW - Stability SP - 131 EP - 43 JF - International journal of pharmaceutics JO - Int J Pharm VL - 460 IS - 1-2 N2 - Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/24239580/Improvement_of_cellular_uptake_in_vitro_antitumor_activity_and_sustained_release_profile_with_increased_bioavailability_from_a_nanoemulsion_platform_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(13)00986-1 DB - PRIME DP - Unbound Medicine ER -