Development of In Situ Gelling Meloxicam-Human Serum Albumin Nanoparticle Formulation for Nose-to-Brain Application.

Gábor Katona,Ilona Gróf,Ildikó Csóka,Bence Sipos,Mária Budai-Szűcs,Piroska Szabó-Révész,Szilvia Veszelka,Mária A Deli,György Tibor Balogh,Balázs Volk

doi:10.3390/pharmaceutics13050646

Abstract

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

Highlights

IntroductionBiodegradable drug carrier for numerous therapeutic agents that have poor water solubility, unsatisfying pharmacokinetics with low circulation halflife, inefficient targetability and even instability in vivo
Albumin is a versatile, biodegradable drug carrier for numerous therapeutic agents that have poor water solubility, unsatisfying pharmacokinetics with low circulation halflife, inefficient targetability and even instability in vivo
Our aim was to optimize an in situ thermo-gelling meloxicam-human serum albumin (MEL-human serum albumin (HSA))-poloxamer 407 (P407) formulation, which can be administered in liquid state into the nostril and to increase resistance of formulation against mucociliarly clearance by sol–gel transition on the nasal mucosa, as well as to improve drug absorption

Summary

Introduction

Biodegradable drug carrier for numerous therapeutic agents that have poor water solubility, unsatisfying pharmacokinetics with low circulation halflife, inefficient targetability and even instability in vivo. Strategies for applying albumin for drug delivery can be classified broadly into exogenous and in situ binding formulations that utilize covalent attachment, non-covalent association, or encapsulation of the drug in the form of albumin-based nanoparticles [1]. The combination of albumin with non-steroid anti-inflammatory drugs (NSAID) can be promising in therapy, which depends on passing the blood–brain barrier (BBB). NSAIDs can have a protective effect in neurodegenerative diseases through different mechanisms.

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