Title: The doxorubicin-entrapped lipoparticles: preparation, characterisation, and efficacy of cellular uptake in human Caco-2 cell

Authors: Chi-Hong Chu; I-Hsun Li; Po-da Hong; Ming-kung Yeh

Addresses: Section of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan ' Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan ' Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, and Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taiwan ' Department of Pharmacy Practice, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, and Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taiwan; School of Pharmacy, National Defence Medical Center and Bureau of Pharmaceutical Affairs, Military of National Defence Medical Affairs Bureau, Taipei, Taiwan

Abstract: Doxorubicin-loaded polyethylene glycol (PEG)-modified lipoparticles with high doxorubicin entrapment has been developed. The preparation technique, characteristics, release profile, cell cytotoxicity, and cellular internalisation of the lipoparticles were evaluated. The PEG-modified lipoparticles prepared by ethanol injection extrusion (100 nm pore size) achieve a population of blank liposomes with a mean size of 125 ± 2.3 nm and a zeta potential of −12.4 ± 1.5 mV. The optimum doxorubicin-loaded lipoparticles system used doxorubicin nanoparticles as core interactions with a 20 : 1 ratio of core and lipid formula consisting of distearoyl phosphatidylcholine/cholesterol/distearoyl phosphoethanolamine-PEG₂₀₀₀)/docosahexaenoic acid at a ratio of 44/36/5/15 and lipid (mg)/ethanol (ml)/water (ml) at a ratio of 25/1/9. The average particle size of the doxorubicin-loaded lipoparticles was 157.7 ± 5.6 nm with a zeta potential of +13.3 mV. Lipoparticle conformation was determined using transmission electron microscopy and field-emission scanning electron microscopy. The doxorubicin encapsulation efficiency was 75.6% for lipoparticles. In vitro release tests indicated that the 50% release time for the doxorubicin-loaded lipoparticles was 7.9 h. A Caco-2 cell model used for evaluating the cytotoxicity and cell uptake efficiency of the doxorubicin-loaded lipoparticles caused significantly less cellular cytotoxicity than doxorubicin solution (p <0.01) and was significantly taken up into cells within 60 min (p < 0.01).

Keywords: formulation; doxorubicin nanoparticles; cellular uptake; doxorubicin-entrapped lipoparticles; human Caco-2 cells; polyethylene glycol; PEG; cell cytotoxicity; nanotechnology; release time.

DOI: 10.1504/IJNT.2013.058115

International Journal of Nanotechnology, 2013 Vol.10 No.10/11, pp.850 - 869

Published online: 08 Dec 2013 *

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