title: Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles.
abstract: BACKGROUND
  This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (Dh= 31 ± 4 nm; ζ = -65 ± 5 mV) loaded in five semi-solid preparations (0.3% w/v), namely Carbopol gel (CP), hydroxyethyl cellulose gel (HEC), carboxymethylcellulose gel (CMC), cetomacrogol cream (Cet) and cold cream was assessed by combining DLS and low-field pulsed NMR data. The in vitro penetration of IONs was studied using human epidermis or isolated stratum corneum (SC).
  
  
  RESULTS
  Reversible and irreversible IONs aggregates were evidenced only in HEC and CMC, respectively. IONs diffused massively through SC preferentially by an intercellular pathway, as assessed by transmission electron microscopy. The semi-solid preparations differently influenced the IONs penetration as compared to the aqueous suspension. Cet cream allowed the highest permeation and the lowest retained amount, while cold cream and CP favored the accumulation into the skin membrane.
  
  
  CONCLUSIONS
  Basic cutaneous semi-solid preparations could be used to administer IONs without affecting their permeation profile if they maintained their physical stability over time. This property is better discriminated by low-field pulsed NMR measurements than the commonly used DLS measurements.
authors.affiliation: Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy.
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Musazzi
authors.affiliation: Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Piazza della Scienza, 2, 20126, Milan, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Santini
authors.affiliation: Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Selmin
authors.affiliation: Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marini
authors.affiliation: Dipartimento di Scienze Biologiche e Cliniche, Università degli Studi di Milano, via G. B. Grassi, 74, 20157, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
authors.affiliation: Dipartimento di Scienze Biologiche e Cliniche, Università degli Studi di Milano, via G. B. Grassi, 74, 20157, Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Allevi
authors.affiliation: Lab. di Nanotecnologie, CNR-Istituto di Scienze e tecnologie Molecolari, via G. Fantoli 16/15, 20138, Milan, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Ferretti
authors.affiliation: Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Piazza della Scienza, 2, 20126, Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Prosperi
authors.affiliation: Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cilurzo
authors.affiliation: Department of Biotechnology and Biosciences, Università degli Studi di Milano-Bicocca, Piazza della Scienza, 2, 20126, Milan, Italy. miriam.colombo@unimib.it.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of Pharmaceutilcal Sciences, Università degli Studi di Milano, via G. Colombo, 71, 20133, Milan, Italy. paola.minghetti@unimi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Minghetti
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002592:Cetomacrogol / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004817:Epidermis / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage*; D005782:Gels / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D012869:Skin Absorption; D063465:Skin Cream / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D005782:Gels; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D002482:Cellulose; D002592:Cetomacrogol; D002266:Carboxymethylcellulose Sodium
keywords: Iron oxide nanoparticles; Nanoparticle stability; Polymer coating; Semi-solid preparation; Skin penetration