Electrospun mats of cyclodextrin‐based polymers for antifungal treatment

A. COSTOYA; F. MONTINI BALLARIN; G.A. ABRAHAM; C. ALVAREZ-LORENZO; A. CONCHEIRO

Santiago de Compostela

Otro; IX Internacional Forum on Advances in Pharmaceutical Technology (CISDEM); 2015

Universidad de Santiago de Compostela - CISDEM

IntroductionElectrospinning is a versatile technique to produce functional fibers with diameters ranging from nano- to micrometers that have been extensively explored as drug carriers due to high loading capacity and high encapsulation efficiency to achieve sustained drug release profiles [1]. Water-soluble cyclodextrin-basedpolymers (polyCDs), prepared via cross-linking of CD units with Epichlorohydrin (EPI), exhibit higher aqueous solubility and low toxicity than parent CDs that make them very interesting in biomedical field. Furthermore, they present properties from CD units like improvement of solubility, stability and bioavailability of hydrophobic drugs through host-guest inclusion complexes (IC) to facilite the release of drugs [2].The aim of this work was to implement an electrospinning procedure to obtain fibers from polyCDs, forming complexes with fluconazole (FLU), mixed with poly-(ε-caprolactone) or poly(N-vynilpyrrolidone) for sustained drug release.MethodsSynthesis of polyCDs: poly-αCD and poly-βCD were prepared following previously reported methods [3][4]. Briefly, 10 g of αCD and 50,7 g of βCD were individually dissolved in 20 mL of 15% and 100 mL of 33% (w/v) NaOH respectively, and were kept overnight at 30°C under stirring. After, EPI was added with molar ratio of 7 for EPI/αCD and 10 for EPI/βCD. Acetone was used to stop the reaction. After phase separation, pH of aqueous solution was adjusted to 10 and 12 for poly-αCD and poly-βCD with 3M HCl. Solutions were kept under stirring at 50°C overnight, and then neutralized and dialyzed against purified water during 4 days. Finally, solutions were freeze-dried to recover polyCDs and characterized by 1H-NMR to estimate the EPI/CD ratio.Formation of Inclusion Complexes: Inclusion complexes were prepared applying a co-evaporation method [5]. Poly-αCD and poly-βCD were individually dissolved in destilled water and mixed with FLU solutions in ethanol. The molar ratio FLU:αCD or βCD units was 1:1. The mixtures were kept in a rotary evaporator at 75°Cand 200 rpm during 1 hour to eliminate the solvents.Electrospinning: Solutions of inclusion complexes or free FLU with PCL or PVP were prepared to electrospin. (FLU-poly-αCD)-IC or (FLU-poly-βCD)-IC with PCL were dissolved in DMF/DCM 4:1 v/v with weight ratios of 40:60 and total polymer concentration was 15% (w/v). (FLU-poly-αCD)-IC or (FLU-poly-βCD)-IC with PVPwere dissolved in ethanol/water 4:6 v/v with ratios of 50:50 and total polymer concentration was 20% (w/v).Results and conclusionsIncorporation of drug into CD cavities was demonstrated by different techniques where signal of the drug was hidden under the amorphous pattern of CD polymers. Bead-free fibrous structures were obtained by electrospinning from the inclusion complexes incorporating PCL or PVP which provided electrospinability to the solutions. Electrospun networks exhibited average fiber diameter of nanometric range, 422 nm for IC/PVP and 837 nm for IC/PCL while fibers of free drug with PCL and PVP had a higher average fiber diameter.