Journal of Colloid and Interface Science 317 (2008) 611–619 www.elsevier.com/locate/jcis The effect of added liposomes on the rheological properties of a hydrogel: A systematic study Spyridon Mourtas a , Maria Haikou a , Maria Theodoropoulou a , Christos Tsakiroglou b , Sophia G. Antimisiaris a,b,∗ a Laboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26510 Rio, Greece b Foundation for Research and Technology Hellas, Institute of Chemical Engineering and High Temperature Chemical Processes, 26504 Rio, Greece Received 19 June 2007; accepted 25 September 2007 Available online 29 September 2007 Abstract Rheological characteristics of liposome-containing-hydrogels were studied. Sonicated unilamellar vesicles (SUV), prepared by probe sonication and multilamellar vesicles (MLV) prepared by thin film hydration were loaded in a hydrogel containing carbopol 974 NF and hydroxyethylcel- lulose (Natrosol 250 HX). Phosphatidylcholine (PC) or hydrogenated-PC (HPC) liposomes, plain or mixed with cholesterol (chol) were used. Static (steady-stress sweep-tests) and dynamic (frequency sweep-tests) rheological measurements were carried out. All gels had a shear thinning behaviour (fitted well by Cross model). Zero-rate shear viscosity and power law index values, revealed that PC liposome addition in the hydrogel had minimum effect on its rheological properties even at the highest lipid concentration used (20 mg/ml). Oppositely, HPC (or HPC/chol) lipo- some addition resulted in significant modulations of the same rheological characteristics (which increased with increasing lipid concentration). HPC liposomes also caused a significant increase in gel relaxation time, which indicates that the elastic character of the gel strengthens as HPC liposome concentration increases. Concluding, liposome composition (membrane rigidity) and lipid concentration, but not liposome size, seem to be very important factors that determine the rheological modulations caused by liposome addition in gels.  2007 Elsevier Inc. All rights reserved. Keywords: Rheological properties; Hydrogels; Gels; Liposomes; Lipid composition; Topical administration; Vaginal 1. Introduction When mucosal or topical (especially vaginal) delivery of li- posome formulations is considered [1,2], the rheological and/or mucoadhesive properties of the liposome dispersions should be adjusted accordingly, depending on the intended route of ad- ministration. This can be achieved by adding gelling agents in liposome dispersions [3,4], resulting in drug-in-liposome-in gel, complex formulations. Such complex gel formulations have been recently studied in our lab in terms of vesicle integrity and drug release kinetics [5,6]. In those studies it was demonstrated [5], that the integrity of liposomal vesicles when dispersed in gels is determined by the rigidity of their lipid membrane. Furthermore, it was ob- * Corresponding author. Fax: +30 2610 996302. E-mail address: santimis@upatras.gr (S.G. Antimisiaris). served that liposomal vesicles are protected from the disruptive effects of specific excipients when dispersed in gels, compared to aqueous media [6]. However, the release of drugs from such complex gels is determined by different factors according to the properties of the drug molecule [5]; for hydrophilic drugs (calcein was used as a model) release from complex gels is re- tarded when rigid-membrane liposomes are used (faster release from PC-compared to DSPC/chol-[liposome-containing] com- plex gels) while the release rate is not affected by the amount of lipid loaded in the gels. Oppositely, for amphiphilic/lipophilic drugs, as griseofulvin (that was used as a model drug), the re- lease from complex gels is determined by the amount of lipid loaded (or better drug loaded, in the form of liposomes); at high drug loading levels (compared to the aqueous solubility of the drug), complex gels release the drug with constant rate irre- spective of the liposome type (PC or DSPC/chol) they contain. In other words, in cases of amphiphilic or lipophilic drugs the lipid concentration added in the gels has a significant impact on 0021-9797/$ – see front matter  2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jcis.2007.09.070