www.elsevier.com/locate/bcdf Available online at www.sciencedirect.com Aggregation behavior of cyclodextrin and cholesterol in simulated human cerebrospinal fluid Istva ´ n Puska ´s a,n , Tı´mea Csilla Czifra a,b,1 ,E ´ va Fenyvesi a , Lajos Szente a a CycloLab Research and Development Laboratory Ltd., 1097 Budapest, Illatos út 7, Hungary b Budapest University of Technology and Economics, 1111 Budapest, Műegyetem rkp. 3-9, Hungary article info Article history: Received 6 September 2013 Received in revised form 15 October 2013 Accepted 16 October 2013 Keywords: Cyclodextrin Cholesterol Niemann-Pick C disease Aggregation Dynamic light scattering abstract A systematic study was performed to reveal the effect on the aggregation behavior of cholesterol solubilized by different cyclodextrins in aqueous media containing cerebrosp- inal fluid (CSF) components such as glucose, urea and inorganic salts. This study intended to mimic physiological conditions regarding concentration and temperature. Co-existing aggregated and non-aggregated structures could be detected in the studied cyclodextrin solutions containing cholesterol. It was found that the CSF components may modify the ratio of the substance being in aggregated or non-aggregated form. By tendency it was recorded that the aggregation state of randomly methylated β-cyclodextrin/cholesterol solutions were susceptible to further aggregation in the presence of CSF components, while 2-hydroxypropyl β-cyclodextrin/cholesterol associates were rather subject to de- aggregation. Larger associates formed from cholesterol and sulfobutylether β-cyclodextrin disintegrated in the presence of the additives, while the non-aggregated complex associates doubled their diameter in the presence of the ionic components of CSF. The results revealed that the interaction of different cyclodextrin derivatives with cholesterol may be modulated by these physiologically present substances. & 2013 Elsevier Ltd. All rights reserved. 1. Introduction Niemann-Pick disease type C (NPC) is an inherited metabolic disorder belonging to the group of lysosomal storage diseases in which different lipids (cholesterol, gangliosides, etc.) accu- mulate within lysosomes. This disease is caused by lack of transporter proteins that are required to translocate these fatty substances within cells, leading to their build-up in the brain and elsewhere in the body such as the spleen and liver. It causes wide range of symptoms, including behavioral problems, learning disabilities and difficulty in moving and speaking. Niemann-Pick disease type C is chronically debilitating and life threatening since the build-up of fatty substances can cause brain damage and swelling of the affected organs. It has been well known from in vitro studies that cyclodex- trins (CDs) may form inclusion complexes with numerous lipid membrane components which are physiologically essential but whose accumulation is responsible for the pathological symp- toms of NPC (Frömming, Fridrich, & Mehnert, 1993; Neufeld et al., 1996; Williams, Mahaguna, & Sriwongjanya, 1998). It has been reported that CDs may extract cholesterol from lipid bilayers (Kiss et al., 2010; López, de Vries, & Marrink, 2013; Monnaert et al., 2004; Yunomae, Arima, Hirayama, & Uekama, 2003). By adequate administering of cyclodextrin (CD), via possible complex forming mechanism, the lipid accumulation might be 2212-6198/$ - see front matter & 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bcdf.2013.10.006 n Corresponding author. Tel.: þ36 1 347 60 77; fax: þ36 1 347 60 68. E-mail address: puskas@cyclolab.hu (I. Puskás). 1 CycloLab Research and Development Laboratory Ltd., 1097 Budapest, Illatos út 7, Hungary. Bioactive Carbohydratesand DietaryFibre 2 (2013)157–163