Pharmaceutical Research

, Volume 26, Issue 3, pp 492–501 | Cite as

Design of Biodegradable Nanoparticles for Oral Delivery of Doxorubicin: In vivo Pharmacokinetics and Toxicity Studies in Rats

  • D. R. Kalaria
  • G. Sharma
  • V. Beniwal
  • M. N. V. Ravi Kumar
Research Paper



Doxorubicin, a potent anticancer drug associated with cardiotoxicity and low oral bioavailability, was loaded into nanoparticles with a view to improve its performance.


Doxorubicin loaded PLGA nanoparticles were prepared by a double emulsion method. The pH dependent stability of nanoparticles in simulated fluids was evaluated. DSC and XRD studies were carried out in order to ascertain the nature of doxorubicin in formulations in conjunction with accelerated stability studies. The in vitro release was investigated in phosphate buffer. The pharmacokinetic and toxicity studies were conducted in rats.


Nanoparticles had an average size of 185 nm, with 49% entrapment at 10% w/w of polymer. The particles displayed good pH dependent stability in the pH range 1.1–7.4. DSC and XRD studies revealed the amorphous nature of doxorubicin in nanoparticles and the accelerated stability studies revealed the integrity of formulations. Initial biphasic release (20%) followed by a sustained release (80%) for 24 days was observed under in vitro conditions. The doxorubicin loaded nanoparticles demonstrated superior performance in vivo as evident by enhanced bioavailability and lower toxicity.


Together, the data indicates the potential of doxorubicin loaded nanoparticles for oral chemotherapy. Further, these formulations could be explored for new indications like leishmaniasis.


bioavailability cardiotoxicity oral delivery oxidative stress 



Area under the curve






Entrapment Efficiency


Institutional Animal Ethics Committee




milli volts






Polydispersity Index


Simulated gastric fluid


Simulated intestinal fluid



DK is grateful to NIPER for providing MS fellowships. Director, NIPER is acknowledged for extending the facility to conduct the work reported in here. Mr. Chandu, Research Scholar, Department of Pharmacology and Toxicology is acknowledged for the help with animal experiments.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • D. R. Kalaria
    • 1
  • G. Sharma
    • 2
  • V. Beniwal
    • 1
  • M. N. V. Ravi Kumar
    • 2
  1. 1.Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research (NIPER)S. A. S. NagarIndia
  2. 2.Strathclyde Institute of Pharmacy and Biomedical SciencesUniversity of StrathclydeGlasgowUK

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