AAPS PharmSciTech

, 20:220 | Cite as

Delivery of Docetaxel to Brain Employing Piperine-Tagged PLGA-Aspartic Acid Polymeric Micelles: Improved Cytotoxic and Pharmacokinetic Profiles

  • Anupama Singh
  • Nagarani Thotakura
  • Bhupinder Singh
  • Shikha Lohan
  • Poonam Negi
  • Deepak Chitkara
  • Kaisar RazaEmail author
Research Article


In this study, poly-(lactic-co-glycolic) acid (PLGA) was conjugated with aspartic acid and was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy. Docetaxel-loaded polymeric micelles were prepared, and piperine was tagged. The neuroblastoma cytotoxicity studies revealed a substantially higher cytotoxic potential of the developed system to that of plain docetaxel, which was further corroborated by cellular uptake employing confocal laser scanning microscopy. The hemocompatible system was able to enhance the pharmacokinetic profile in terms of 6.5-fold increment in bioavailability followed by a 3.5 times increase in the retention time in comparison with the plain drug. The single-point brain bioavailability of docetaxel was amplified by 3.3-folds, signifying a better uptake and distribution to brain employing these carriers. The findings are unique as the physically adsorbed piperine was released before the DTX, increasing the propensity of curbing the CYP3A4 enzyme, which plays a vital role in the degradation of docetaxel. Meanwhile, piperine might have compromised the P-gp efflux mechanism, which can be ascribed to the enhanced retention of the drug at the target site. The elevated target site concentrations and extended residence by a biocompatible nanocarrier supplemented with co-delivery of piperine inherit immense promises to deliver this BCS class IV drug more safely and effectively.


bioavailability aspartic acid conjugation co-administration anticancer activity brain delivery 


Funding Information

The study was financially supported by the Science and Engineering Research Board, Department of Science and Technology (DST), New Delhi, India (YSS/2014/000485).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Anupama Singh
    • 1
  • Nagarani Thotakura
    • 1
  • Bhupinder Singh
    • 2
    • 3
  • Shikha Lohan
    • 2
  • Poonam Negi
    • 4
  • Deepak Chitkara
    • 5
  • Kaisar Raza
    • 1
    Email author
  1. 1.Department of Pharmacy, School of Chemical Sciences and PharmacyCentral University of RajasthanDistt. AjmerIndia
  2. 2.UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and NanocompositesPanjab UniversityChandigarhIndia
  3. 3.Division of Pharmaceutics, University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia
  4. 4.School of Pharmaceutical SciencesShoolini UniversitySolanIndia
  5. 5.Department of PharmacyBirla Institute of Technology and Science-Pilani (BITS)PilaniIndia

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