Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment

A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found t...

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Veröffentlicht in:AAPS PharmSciTech 2018-11, Vol.19 (8), p.3839-3849
Hauptverfasser: Raikwar, Sarjana, Vyas, Sonal, Sharma, Rajeev, Mody, Nishi, Dubey, Surbhi, Vyas, Suresh P.
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Sprache:eng
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Zusammenfassung:A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0.04, +23.4 ± 0.3 mV and 88.3 ± 0.2% (PTX), and 89.6 ± 0.5% (DOX) respectively. In vitro drug release study of optimized formulation was carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed 75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s) were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest GI 50 value of FA-D-P NLCs which was 1.04 ± 0.012 μg/ml, followed by D-P NLCs and D-P solution with GI 50 values of 3.12 ± 0.023 and 3.89 ± 0.007 μg/ml, respectively. Findings indicated that the folic acid-conjugated PTX and DOX co-loaded NLCs exhibited lower GI 50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.
ISSN:1530-9932
1530-9932
DOI:10.1208/s12249-018-1185-y