Incorporation of biodegradable nanoparticles into human
airway epithelium cells
in vitro study of the suitability
as a vehicle for drug or gene delivery in pulmonary diseases
and C.v. Mallinckrodt
Department of Pulmonology, Medical Clinic of Johann-Wolfgang-Goethe University Frankfurt am Main,
Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
Institute for Pharmaceutical Technology, Biocenter of Johann-Wolfgang-Goethe University, Marie-Curie-Strasse 9, 60439 Frankfurt, Germany
Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Butenandstrasse 5-13, 81377 Munich, Germany
Received 30 March 2004
Available online 22 April 2004
Purpose. Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues.
Surface modiﬁcations can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum
albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated in vitro on primary
airway epithelium cells and the cell line 16HBE14o-. Methods. The uptake of nanoparticles into these cells was examined by confocal
laser scan microscopy (CLSM) and ﬂow cytometry (FACS). Further the cytotoxicity of nanoparticles was evaluated by an LDH-
release-test and the inﬂammatory potential of the nanoparticles was assessed by measuring IL-8 release. Results. CLSM and FACS
experiments showed that the nanoparticles were incorporated into bronchial epithelial cells provoking little or no cytotoxicity and
no inﬂammation as measured by IL-8 release. Conclusions. Based on their low cytotoxicity and the missing inﬂammatory potential
in combination with an eﬃcient uptake in human bronchial epithelial cells, protein-based nanoparticles are suitable drug and gene
carriers for pulmonary application.
Ó 2004 Elsevier Inc. All rights reserved.
Keywords: Nanoparticles; Gelatin; Human serum albumin; Polyalkylcyanoacrylates; IL-8; Airway epithelium cells; Bronchial epithelium cells; Drug
delivery; Gene delivery; Particulate carrier system; Particulate delivery system
Nanoparticles as drug carrier systems are able to in-
crease intracellular drug and gene delivery in vitro and
in vivo to various tissues [1–12]. This has contributed to
protection of drugs or DNA from degradation by the
envelopment in or binding to a nanoparticle prepara-
tion. Additionally, nanoparticles seem to be well suited
to traverse cellular membranes. Described applications
range from increasing the bioavailability of antiretrovi-
ral drugs , over gene and oligonucleotide transfer
[5,13] to desensibilisation in peanut allergy .
Speaking about gene therapy, especially for diseases
of the lung, viral vectors are plagued by safety concerns
and non-viral agents lack the necessary in vivo eﬃciency
so that a deﬁnitive vehicle is still in demand [14–16].
Nanoparticles have advantages over viral systems such
as safety, low cost, stability, ease of manufacturing, and
high ﬂexibility concerning the size of the transgene to be
delivered. Their disadvantages include reduced eﬃciency
of transgene delivery, toxicity at higher concentrations,
and interactions with negatively charged molecules in
serum on the cell surface and, as a consequence, poor
delivery to the targeted cells . However, protein
nanoparticle preparations recently seem to overcome
these obstacles [11,12,18]. Especially human serum
Corresponding author. Fax: +49-69-6301-4749.
E-mail address: email@example.com (M. Brzoska).
0006-291X/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
Biochemical and Biophysical Research Communications 318 (2004) 562–570