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AAPS PharmSciTech

, Volume 19, Issue 8, pp 3839–3849 | Cite as

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

  • Sarjana Raikwar
  • Sonal Vyas
  • Rajeev Sharma
  • Nishi Mody
  • Surbhi Dubey
  • Suresh P. Vyas
Research Article
  • 82 Downloads

Abstract

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 GI50 value of FA-D-P NLCs which was 1.04 ± 0.012 μg/ml, followed by D-P NLCs and D-P solution with GI50 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 GI50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.

Keywords

Nanostructured lipid carrier(s) Paclitaxel Doxorubicin Folic acid resistant tumor 

Abbreviations

P

paclitaxel

D

doxorubicin

FA

folic acid

FA-D-P NLCs

folic acid-doxorubicin-paclitaxel nanostructured lipid carrier(s) formulation

D-P NLCs

doxorubicin-paclitaxel nanostructured lipid carrier(s) formulation

B-NLCs

plain nanostructured lipid carrier(s) formulation

D-P- Sol

doxorubicin-paclitaxel solution

D-sol

doxorubicin-solution

P-sol

paclitaxel solution

ADR

adriamycin

Notes

Acknowledgments

We also acknowledge the Sophisticated Instruments Centre, Dr. H.S. Gour Central University, Sagar (India), for providing the SEM analysis and TEM analysis. The authors would also like to acknowledge Neon Laboratories, Mumbai (India), for providing the gift sample of paclitaxel and M/s. Sun Pharma Advanced Research Centre (SPARC) Vadodara, Gujarat (India), for providing the gift samples of doxorubicin, as well as Lipoid (Germany) for the generous gift sample of DSPE. We sincerely acknowledge Dr. Jyoti Kode, Tata Memorial Center-ACTREC, Kharghar, Navi Mumbai (India) for her support in carrying out the ex vivo studies.

Funding Information

Financial support was provided by the All India Council of Technical Education (AICTE), New Delhi (India) (Sarjana Raikwar).

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  1. 1.Drug delivery Research Laboratory, Department of Pharmaceutical SciencesDr. H. S. Gour Central UniversitySagarIndia
  2. 2.Department of Pathology, Index Medical CollegeHospital & Research CentreIndoreIndia

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