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


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.

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

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Correspondence to Kaisar Raza.

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Singh, A., Thotakura, N., Singh, B. et al. Delivery of Docetaxel to Brain Employing Piperine-Tagged PLGA-Aspartic Acid Polymeric Micelles: Improved Cytotoxic and Pharmacokinetic Profiles. AAPS PharmSciTech 20, 220 (2019).

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  • bioavailability
  • aspartic acid conjugation
  • co-administration
  • anticancer activity
  • brain delivery