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Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer

  • Preshita Desai
  • Arvind Thakkar
  • David Ann
  • Jeffrey Wang
  • Sunil PrabhuEmail author
Original Article
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Abstract

Pancreatic cancer (PC), currently the third leading cause of cancer-related deaths in the USA, is projected to become the second leading cause, behind lung cancer, by 2020. The increasing incidence, low survival rate, and limited treatment opportunities necessitate the use of alternative approaches such as chemoprevention, to tackle PC. In this study, we report significant synergistic chemoprevention efficacy for the first time from a low-dose combination of a classical antihistaminic drug, Loratadine (LOR) and a neutraceutical compound, Sulforaphane (SFN) using a self-microemulsifying drug delivery system (SMEDDS) formulation. The formulation was developed using Quality by Design approach (globule size, 95.13 ± 7.9 nm; PDI, 0.17 ± 0.04) and revealed significant (p < 0.05) enhancement in the in vitro dissolution profile confirming the enhanced solubility of BCS class II drug LOR with SMEDDS formulation. The LOR-SFN combination revealed ~ 40-fold reduction in IC50 concentration compared to LOR alone in MIA PaCa-2 and Panc-1 cell lines respectively, confirming the synergistic enhancement in chemoprevention. Further, the nanoformulation resulted in ~ 7-fold and ~ 11-fold reduction in IC50 values compared to LOR-SFN combination. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDs with SFN shows significantly enhanced chemopreventive efficacy of PC.

Keywords

Pancreatic cancer Chemoprevention Loratadine Sulforaphane Synergism Self-microemulsifying drug delivery system 

Notes

Funding

This work was supported by the National Institutes of Health [grant num: 1R15CA182834-01].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  • Preshita Desai
    • 1
  • Arvind Thakkar
    • 2
  • David Ann
    • 3
  • Jeffrey Wang
    • 1
  • Sunil Prabhu
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyWestern University of Health SciencesPomonaUSA
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyUniversity of New EnglandPortlandUSA
  3. 3.Department of Diabetes and Metabolic Diseases Research, Beckman Research InstituteCity of HopeDuarteUSA

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