Cream formulation impact on topical administration of engineered colloidal nanoparticles.

Benedetta Santini,Ivan Zanoni,Fabio Corsi,Luca Palugan,Roberta Marzi,Miriam Colombo,Marzia Bedoni,Francesca Granucci,Furio Gramatica,Clara Cigni

doi:10.1371/journal.pone.0126366

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.

Highlights

Nanomaterials, which size is included within 1–100 nm range, hold tremendous potential in biomedical applications thanks to the favorable combination of unique chemical and physical size-dependent properties [1,2]
magnetic (iron oxide) nanoparticles (MNP) were coated with an amphiphilic polymer (PMA), obtained by reacting poly(isobutylene-alt-1-tetradecene-maleic anhydride) with an amount of dodecylamine sufficient to react with 75% of anhydride groups (Fig 1B) [24]
We developed a nanoparticle scaffold that could be formulated both in suspension and in w/o cream, which might be useful for topical application

Summary

Introduction

Nanomaterials, which size is included within 1–100 nm range, hold tremendous potential in biomedical applications thanks to the favorable combination of unique chemical and physical size-dependent properties [1,2]. Drug delivery nanosystems are meant to improve the biopharmaceutical properties of existing drugs that often exhibit a limited effectiveness in therapy. Such limitations include solidand suspension-state instability, poor solubility and poor drug absorption that could lead to low bioavailability and insufficient targeting efficiency that could lead to unfavorable ratio between the amount of the administered drug and the concentration at the target tissue [7,8,9]. The conventional transdermal drug delivery methods are limited by skin barrier properties according to the “brick and mortar model” (stratum corneum) that prevents excessive water loss and offers an efficient protective tissue against exogenous chemical, physical and mechanical stimuli and pathogens [15]

Methods

Results

Conclusion