title: Cream formulation impact on topical administration of engineered colloidal nanoparticles.
abstract: In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide) nanoparticles (MNP) coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP) cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Santini
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy; Division of Gastroenterology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Unit of Cell Signalling and Innate Immunity, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zanoni
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Marzi
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Cigni
authors.affiliation: Laboratorio di Nanomedicina e Biofotonica Clinica, Fondazione Don Carlo Gnocchi ONLUS, Milano, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Bedoni
authors.affiliation: Laboratorio di Nanomedicina e Biofotonica Clinica, Fondazione Don Carlo Gnocchi ONLUS, Milano, Italy.
authors.forename: Furio
authors.initials: F
authors.lastname: Gramatica
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Palugan
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Corsi
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy; Unit of Cell Signalling and Innate Immunity, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Granucci
authors.affiliation: NanoBioLab, Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milano, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D003102:Colloids; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D004364:Pharmaceutical Preparations