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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

ABSTRACT

Purpose

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

Methods

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.

Results

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.

Conclusions

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.

KEY WORDS

biodistribution nanoparticles oral poly(anhydride) toxicity 

ABBREVIATIONS

%ID/g

percentage of injected dose per gram

99mTc

technetium-99m

ALT

alanine transaminase

AST

aspartate transaminase

Bw

body weight

CT

computed tomography

Hb

hemoglobin

HCT

hematocrit

HPCD

2-hydroxipropyl-β-cyclodextrin

ITLC

instant thin layer chromatography

MCH

mean corpuscular hemoglobin

MCHC

mean corpuscular hemoglobin concentration

MCV

mean corpuscular volume

NP

conventional poly(anhydride) nanoparticles

NP-HPCD

nanoparticles containing 2-hydroxypropyl-β-cyclodextrin

NP-PEG

pegylated poly(anhydride) nanoparticles

PEG

poly(ethylene glycol) 6000

PLT

platelet count

PVM/MA

copolymer of methyl vinyl ether and maleic anhydride

RBC

red blood corpuscles count

SPECT-CT

single-photon emission computed tomography

WBC

white blood corpuscles count

Notes

ACKNOWLEDGMENTS AND DISCLOSURES

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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