Formulation and optimization of itraconazole polymeric lipid hybrid nanoparticles (Lipomer) using Box Behnken design.

Balaram Gajra,Ravi Patel,Chintan Dalwadi

doi:10.1186/s40199-014-0087-0

Abstract

BackgroundThe objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability.MethodThe Polymeric lipid hybrid nanoparticle formulation was prepared by the emulsification solvent evaporation method and 3 factor 3 level Box Behnken statistical design was used to optimize and derive a second order polynomial equation and construct contour plots to predict responses. Biodegradable Polycaprolactone, soya lecithin and Poly vinyl alcohol were used to prepare PLHNs. The independent variables selected were lipid to polymer ratio (X1) Concentration of surfactant (X2) Concentration of the drug (X3).ResultThe Box-Behnken design demonstrated the role of the derived equation and contour plots in predicting the values of dependent variables for the preparation and optimization of Itraconazole PLHNs. Itraconazole PLHNs revealed nano size (210 ± 1.8 nm) with an entrapment efficiency of 83 ± 0.6% and negative zeta potential of −11.7 mV and also enhance the permeability of itraconazole as the permeability coefficient (Papp) and the absorption enhancement ratio was higher.ConclusionThe tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer’s patch or paracellular pathway which was proven by confocal microscopy.

Highlights

The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability
The tunable particle size, surface charge, and favourable encapsulation efficiency with a sustained drug release profile of PLHNs suggesting that it could be promising system envisioned to increase the bioavailability by improving intestinal permeability through lymphatic uptake, M cell of payer’s patch or paracellular pathway which was proven by confocal microscopy
Optimization of polymer lipid hybrid nanoparticle by box-behnken design All the batches of PLHNs were evaluated for the particle size (Y1) and entrapment efficiency (Y2) and the results are shown in the Table 2

Summary

Introduction

The objective of the study was to formulate and to investigate the combined influence of 3 independent variables in the optimization of Polymeric lipid hybrid nanoparticles (PLHNs) (Lipomer) containing hydrophobic antifungal drug Itraconazole and to improve intestinal permeability. From many forms of the infection, invasive fungal infections have become more common in recent years, with a nearly 500% growth in the incidence of blood stream infection with Candida spp. since the 1980 [1]. The azole antifungal agents represent a major drug class in the treatment of wide variety of fungal infections. These drugs can be Itraconazole (ITZ) is a potent triazole antifungal with broad spectrum of activity against fungal species and more efficacious for the treatment of both systemic and superficial fungal infections [3]. ITZ is widely clinically used for a variety of serious fungal infections in normal and immunocompromised hosts, including Aspergillosis, Cryptococcus, Candida, Blastomyces, disseminated Penicillium mameffei infections and Histoplasma capsulatum var. ITZ is widely clinically used for a variety of serious fungal infections in normal and immunocompromised hosts, including Aspergillosis, Cryptococcus, Candida, Blastomyces, disseminated Penicillium mameffei infections and Histoplasma capsulatum var. capsulatum and it has less nephrotoxicity than Amphotericin B [4].

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