Pharmaceutical Research

, 35:221 | Cite as

Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy

  • Roselena Silvestri Schuh
  • Juliana Bidone
  • Edina Poletto
  • Camila Vieira Pinheiro
  • Gabriela Pasqualim
  • Talita Giacomet de Carvalho
  • Mirian Farinon
  • Dirnete da Silva Diel
  • Ricardo Machado Xavier
  • Guilherme Baldo
  • Ursula Matte
  • Helder Ferreira TeixeiraEmail author
Research Paper



This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy.


Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogenization, and assessed in vitro on human fibroblasts from MPS I patients and in vivo on MPS I mice for IDUA production and gene expression.


The physicochemical results showed that the presence of DSPE-PEG in the formulations led to smaller and more stable droplets even when submitted to dilution in simulated nasal medium (SNM). In vitro assays showed that pIDUA/NE-PEG complexes were internalized by cells, and led to a 5% significant increase in IDUA activity, besides promoting a two-fold increase in IDUA expression. The NA of pIDUA/NE-PEG complexes to MPS I mice demonstrated the ability to reach the brain, promoting increased IDUA activity and expression in this tissue, as well as in kidney and spleen tissues after treatment. An increase in serum IL-6 was observed after treatment, although with no signs of tissue inflammatory infiltrate according to histopathology and CD68 assessments.


These findings demonstrated that pIDUA/NE-PEG complexes could efficiently increase IDUA activity in vitro and in vivo after NA, and represent a potential treatment for the neurological impairment present in MPS I patients.


Gene therapy mucopolysaccharidosis type I nanoemulsion nasal administration nonviral vectors 



Blank cationic nanoemulsions


Blank cationic nanoemulsions containing DSPE-PEG




1,2-dioleoyl-sn-glycero-3-trimethylammonium propane


1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]






Medium Chain Triglycerides


Nasal administration


Plasmid encoding for IDUA protein


Nanoemulsion complexed with pIDUA


Nanoemulsion containing DSPE-PEG complexed with pIDUA


Simulated nasal medium



Authors would like to thank the Brazilian National Council for Scientific and Technological Development (CNPq), Foundation for Research Support of the State of Rio Grande do Sul (FAPERGS, #17/2551–0001273-9), and HCPA Foundation for Incentive of Research (FIPE/HCPA, #150215) for the financial support. J. Bidone wishes to thank the Foundation for Research Support of the State of Rio Grande do Sul (DOCFIX/FAPERGS) and R. S. Schuh would like to thank CNPq (#151021/2018–0) for their postdoctoral grant. H. F. Teixeira, G. Baldo, and U. Matte are recipients of CNPq research fellowship. The authors have made substantial contributions to all of the following: R. S. Schuh and J. Bidone contributed to the conception and design of the study. G. Pasqualim, T. G. de Carvalho, É. Poletto, C. V. Pinheiro, D. S. Diel, M. Farinon, and R. M. Xavier contributed to the acquisition of data, analysis, and interpretation of data. G. Baldo, U. Matte, and H. F. Teixeira contributed to drafting the article and revising it critically for important intellectual content. All authors approved the final version to be submitted. All institutional and national guidelines for the care and use of patients’ material were followed and all patients and/or their caregivers gave written informed consent for this study. All institutional and national guidelines for the care and use of laboratory animals were followed (Hospital de Clínicas de Porto Alegre Ethics Committee #15–0215). All authors declare that they have no conflict of interest.

Supplementary material

11095_2018_2503_MOESM1_ESM.docx (533 kb)
ESM 1 (DOCX 533 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Roselena Silvestri Schuh
    • 1
    • 2
  • Juliana Bidone
    • 1
  • Edina Poletto
    • 2
    • 3
  • Camila Vieira Pinheiro
    • 2
  • Gabriela Pasqualim
    • 2
    • 3
  • Talita Giacomet de Carvalho
    • 2
    • 3
  • Mirian Farinon
    • 4
  • Dirnete da Silva Diel
    • 1
    • 3
  • Ricardo Machado Xavier
    • 4
  • Guilherme Baldo
    • 2
    • 3
  • Ursula Matte
    • 2
    • 3
  • Helder Ferreira Teixeira
    • 1
    Email author
  1. 1.Pharmaceutical Sciences Graduate ProgramUFRGSPorto AlegreBrazil
  2. 2.Gene Therapy CenterHospital de Clinicas de Porto AlegrePorto AlegreBrazil
  3. 3.Genetics and Molecular Biology Graduate ProgramUFRGSPorto AlegreBrazil
  4. 4.Reumathology ServiceHospital de Clínicas de Porto AlegrePorto AlegreBrazil

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