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Efficacy and Pharmacokinetic Considerations of Loratadine Nanoformulations and its Combinations for Pancreatic Cancer Chemoprevention

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Abstract

Purpose

Pancreatic cancer (PC) is predicted to become the second leading cause of cancer associated deaths by 2020. Earlier, we confirmed the development and efficacy of our novel Loratadine Self-Microemulsifying-Drug-Delivery-System - Sulforaphane (LOR SMEDDS -SFN) nanoformulation in PC chemoprevention. In this report, we extend our studies to evaluate the PC chemoprevention efficacy of LOR SMEDDS – SFN.

Methods

The nanoformulation was subjected to in vitro colony formation assays, in vivo oral pharmacokinetics and stability studies.

Results

The colony formation assay using Panc–1 PC cells demonstrated a survival fraction of 0.74 with LOR-SFN (p < 0.001) which further reduced to 0.35 with LOR SMEDDS-SFN treatment (p  < 0.0001) confirming the synergistic chemoprevention efficacy of the nanoformulation. Further, the oral pharmacokinetic studies of LOR SMEDDS-SFN showed 4-fold and 9-fold increase in Cmax (503.2 ± 5.8 ng/mL) and oral bioavailability (20,274.8 ± 3711.0 ng·h/mL) for LOR compared to LOR-SFN combination respectively assuring the enhanced performance by the SMEDDS. Additionally, the formulation exhibited statistically non-significant alteration in globule size, zeta potential, drug content and in vitro drug release during stability studies confirming its stability and pharmaceutical acceptability.

Conclusion

Our studies have demonstrated a potential of LOR SMEDDS-SFN nanoformulation as an effective PC chemoprevention strategy.

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References

  1. AmericanCancerSociety. Key Statistics for Pancreatic Cancer 2019 [updated 8/8/2019. Available from: https://www.cancer.org/cancer/pancreatic-cancer/about/key-statistics.html.

  2. CancerNet. Pancreatic Cancer: Statistics 2019 [Available from: https://www.cancer.net/cancer-types/pancreatic-cancer/statistics.

  3. ROSENZWEIG A. Increase in Pancreatic Cancer Diagnoses Expected in 2019 2019 [Available from: https://www.pancan.org/news/increase-in-pancreatic-cancer-diagnoses-expected-in-2019/.

  4. AmericanCancerSociety. Survival Rates for Pancreatic Cancer 2019 [Available from: https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html.

  5. NationalCancerInstitute. Cancer Stat Facts: Pancreatic Cancer 2019 [Available from: https://seer.cancer.gov/statfacts/html/pancreas.html.

  6. Benzel J, Fendrich V. Chemoprevention and treatment of pancreatic cancer: update and review of the literature. Digestion. 2018;97(4):275–87.

    Article  CAS  Google Scholar 

  7. Desai P, Ann D, Wang J, Prabhu S. Pancreatic cancer: recent advances in nanoformulation-based therapies. Crit Rev Ther Drug Carrier Syst. 2019;36(1):59–91.

    Article  Google Scholar 

  8. Desai P, Thakkar A, Ann D, Wang J, Prabhu S. Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer. Drug Deliv Transl Res. 2019;9(3):641–51.

    Article  CAS  Google Scholar 

  9. Grandhi BK, Thakkar A, Wang J, Prabhu S. A novel combinatorial nanotechnology-based oral chemopreventive regimen demonstrates significant suppression of pancreatic cancer neoplastic lesions. Cancer Prev Res (Phila). 2013;6(10):1015–25.

    Article  CAS  Google Scholar 

  10. Bosland MC. How to rationally identify promising cancer chemoprevention agents. JNCI: Journal of the National Cancer Institute. 2015;107(12).

  11. Stan SD, Singh SV, Brand RE. Chemoprevention strategies for pancreatic cancer. Nature Reviews Gastroenterology &Amp; Hepatology. 2010;7:347.

  12. Zhou P, Cheng SW, Yang R, Wang B, Liu J. Combination chemoprevention: future direction of colorectal cancer prevention. Eur J Cancer Prev. 2012;21(3):231–40.

    Article  CAS  Google Scholar 

  13. Thakkar A, Chenreddy S, Thio A, Khamas W, Wang J, Prabhu S. Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice. Int J Nanomedicine. 2016;11:3265–76.

    Article  CAS  Google Scholar 

  14. Thakkar A, Desai P, Chenreddy S, Modi J, Thio A, Khamas W, et al. Novel nano-drug combination therapeutic regimen demonstrates significant efficacy in the transgenic mouse model of pancreatic ductal adenocarcinoma. Am J Cancer Res. 2018;8(10):2005–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Akula S, Gurram AK, Devireddy SR. Self-microemulsifying drug delivery systems: an attractive strategy for enhanced therapeutic profile. Int Sch Res Notices. 2014;2014:964051.

    PubMed  PubMed Central  Google Scholar 

  16. Desai PP, Date AA, Patravale VB. Overcoming poor oral bioavailability using nanoparticle formulations – opportunities and limitations. Drug Discov Today Technol. 2012;9(2):e87–95.

    Article  CAS  Google Scholar 

  17. Noehr-Jensen L, Damkier P, Bidstrup TB, Pedersen RS, Nielsen F, Brosen K. The relative bioavailability of loratadine administered as a chewing gum formulation in healthy volunteers. Eur J Clin Pharmacol. 2006;62(6):437–45.

    Article  CAS  Google Scholar 

  18. Hanlon N, Coldham N, Gielbert A, Kuhnert N, Sauer MJ, King LJ, et al. Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat. Br J Nutr. 2008;99(3):559–64.

    Article  CAS  Google Scholar 

  19. Thakkar A, Chenreddy S, Wang J, Prabhu S. Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention. Int J Oncol. 2015;46(4):1827–34.

    Article  CAS  Google Scholar 

  20. Chen C, Hanson E, Watson JW, Lee JS. P-glycoprotein limits the brain penetration of nonsedating but not sedating H1-antagonists. Drug Metab Dispos. 2003;31(3):312–8.

    Article  CAS  Google Scholar 

  21. Jaiswal P, Aggarwal G, Sl H, Kaur A. Bioavailability enhancement of poorly soluble drugs by SMEDDS: a review. Journal of Drug Delivery & Therapeutics. 2013;3:98–109.

    Article  CAS  Google Scholar 

  22. Shono Y, Nishihara H, Matsuda Y, Furukawa S, Okada N, Fujita T, et al. Modulation of intestinal P-glycoprotein function by cremophor EL and other surfactants by an in vitro diffusion chamber method using the isolated rat intestinal membranes. J Pharm Sci. 2004;93(4):877–85.

    Article  CAS  Google Scholar 

  23. Zhang H, Yao M, Morrison RA, Chong S. Commonly used surfactant, tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res. 2003;26(9):768–72.

    Article  CAS  Google Scholar 

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Funding

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

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California, 91766, USA

    Preshita Desai, Jeffrey Wang & Sunil Prabhu

  2. Department of Pharmaceutical Sciences, College of Pharmacy, Marshall B. Ketchum University, Fullerton, California, 92831, USA

    Kevin Zhijun Wang

  3. Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope, Duarte, California, 91010, USA

    David Ann

Authors
  1. Preshita Desai
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  2. Kevin Zhijun Wang
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  3. David Ann
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  5. Sunil Prabhu
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Correspondence to Sunil Prabhu.

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Desai, P., Wang, K.Z., Ann, D. et al. Efficacy and Pharmacokinetic Considerations of Loratadine Nanoformulations and its Combinations for Pancreatic Cancer Chemoprevention. Pharm Res 37, 21 (2020). https://doi.org/10.1007/s11095-019-2737-x

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  • DOI: https://doi.org/10.1007/s11095-019-2737-x

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