Pharmaceutical Research

, Volume 29, Issue 9, pp 2615–2627 | Cite as

Toxicity Studies of Poly(Anhydride) Nanoparticles as Carriers for Oral Drug Delivery

  • Patricia Ojer
  • Adela López de Cerain
  • Paloma Areses
  • Ivan Peñuelas
  • Juan M. Irache
Research Paper



To evaluate the acute and subacute toxicity of poly(anhydride) nanoparticles as carriers for oral drug/antigen delivery.


Three types of poly(anhydride) nanoparticles were assayed: conventional (NP), nanoparticles containing 2-hydroxypropyl-β-cyclodextrin (NP-HPCD) and nanoparticles coated with poly(ethylene glycol) 6000 (PEG-NP). Nanoparticles were prepared by a desolvation method and characterized in terms of size, zeta potential and morphology. For in vivo oral studies, acute and sub-acute toxicity studies were performed in rats in accordance to the OECD 425 and 407 guidelines respectively. Finally, biodistribution studies were carried out after radiolabelling nanoparticles with 99mtechnetium.


Nanoparticle formulations displayed a homogeneous size of about 180 nm and a negative zeta potential. The LD50 for all the nanoparticles tested was established to be higher than 2000 mg/kg bw. In the sub-chronic oral toxicity studies at two different doses (30 and 300 mg/kg bw), no evident signs of toxicity were found. Lastly, biodistribution studies demonstrated that these carriers remained in the gut with no evidences of particle translocation or distribution to other organs.


Poly(anhydride) nanoparticles (either conventional or modified with HPCD or PEG6000) showed no toxic effects, indicating that these carriers might be a safe strategy for oral delivery of therapeutics.


biodistribution nanoparticles oral poly(anhydride) toxicity 



percentage of injected dose per gram




alanine transaminase


aspartate transaminase


body weight


computed tomography








instant thin layer chromatography


mean corpuscular hemoglobin


mean corpuscular hemoglobin concentration


mean corpuscular volume


conventional poly(anhydride) nanoparticles


nanoparticles containing 2-hydroxypropyl-β-cyclodextrin


pegylated poly(anhydride) nanoparticles


poly(ethylene glycol) 6000


platelet count


copolymer of methyl vinyl ether and maleic anhydride


red blood corpuscles count


single-photon emission computed tomography


white blood corpuscles count



This work was supported by the Ministry of Science and Innovation in Spain (projects SAF2008-02538) and Caja Navarra Foundation (Grant 10828). Patricia Ojer was also financially supported by a grant from the Department of Education of the Gobierno de Navarra in Spain.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Patricia Ojer
    • 1
    • 2
  • Adela López de Cerain
    • 2
  • Paloma Areses
    • 3
  • Ivan Peñuelas
    • 3
  • Juan M. Irache
    • 1
  1. 1.Department of Pharmacy and Pharmaceutical TechnologyUniversity of NavarraPamplonaSpain
  2. 2.Department of Nutrition and Food Sciences, Physiology and ToxicologyUniversity of NavarraPamplonaSpain
  3. 3.Radiopharmacy Unit, Department of Nuclear MedicineUniversity Clinic of NavarraPamplonaSpain

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