Preparation and optimization of polymeric micelles as an oral drug delivery system for deferoxamine mesylate: in vitro and ex vivo studies

Abstract

Deferoxamine mesylate (DFO) is administered as a slow subcutaneous or intravenous infusion due to its poor oral bioavailability and lack of dose proportionality. The aim of the present study was to prepare and optimize polymeric micelles containing DFO, as an oral drug delivery system for increasing permeability and oral bioavailability. Based on a full factorial design with three variables in two levels, eight polymeric micelle formulations were made using film hydration method. Two polymers including 0.1% of carbomer 934 and Poloxamer ® P 407 and two blends of surfactant + co-surfactant including 1 and 2 fold of critical micelle concentration of Labrafil ® + Labrasol ® and Tween 80 + Span 20 were used to prepare polymeric micelles. The effect of variables on particle size (PS), entrapment efficiency (EE), drug release, thermal behavior, in vitro iron bonding and ex vivo rat intestinal permeability were evaluated. The PS of polymeric micelles was less than 83 nm that showed 80% EE with continuous drug release pattern. The change in type of polymer from carbomer to Ploxamer ® significantly increased drug release. All polymeric micelles increased the iron-bonding ability of DFO compared to control. This could be due to surfactants that can play an important role in this ability. Polymeric micelles increased drug permeability through intestine more than 2.5 folds compared to control mainly affected by polymer type. Optimized polymeric micelle consists of Tween 80 and Span 20 with 1.35 folds of critical micelle concentration and Poloxamer ® demonstrated 97.32% iron bonding and a 3-fold increase in permeation through the rat intestine compared with control.

Development and In Vitro Evaluation of 2-Methoxyestradiol Loaded Polymeric Micelles for Enhancing Anticancer Activities in Prostate Cancer

“…Meanwhile, it was noted that the higher TW80 (surfactant) concentration decreased PS. However, this result was opposite to those of reported studies where higher surfactant concentration increased the PS of PMs [ 24 ]. Nevertheless, in general, higher surfactant concentration generally results in lower particle size of nanostructures [ 25 ].…”

Comprehensive Study of Atorvastatin Nanostructured Lipid Carriers through Multivariate Conceptualization and Optimization

“…A larger PS was developed when elevated concentrations of the surfactant were used in the aqueous phase, causing a higher viscosity [43]. Likewise, increasing the total lipid concentration as well as decreasing the percentage of solid lipids in the solid/liquid lipid mixture led to a large PS.…”

<p>Improvements in the Oral Absorption and Anticancer Efficacy of an Oxaliplatin-Loaded Solid Formulation: Pharmacokinetic Properties in Rats and Nonhuman Primates and the Effects of Oral Metronomic Dosing on Colorectal Cancer</p>

“…51,52 Furthermore, P188 and Labrasol, which are used as an amphiphilic block copolymer and a surfactant, respectively, self-assemble as micelles at concentrations above the critical micellar concentration. 53,54 Thus, complex formation of OP with DLM, along with P188 and Labrasol as dispersants, results in the formation of stable micelles in the aqueous solution. In addition, transmission electron microscopy images of ODSF demonstrated the formation of spherical and homogenous nano-sized micelles, <200 nm in diameter ( Figure 2C).…”