IEEE TRANSACTIONS ON MAGNETICS, VOL. 53, NO. 11, NOVEMBER 2017 5200604 Functionalization of Magnetic Hollow Spheres With (3-Aminopropyl)Triethoxysilane for Controlled Drug Release P. B. Patil 1 , V. C. Karade 2 , P. P. Waifalkar 3 , Subasa C. Sahoo 4 , P. Kollu 5,6 , M. S. Nimbalkar 7 , A. D. Chougale 8 , and P. S. Patil 2,3 1 Department of Physics, The New College, Kolhapur 416012, India 2 School of Nanoscience and Biotechnology, Shivaji University, Kolhapur 416004, India 3 Department of Physics, Shivaji University, Kolhapur 416004, India 4 Department of Physics, Central University of Kerala, Kasaragod, (KL)-671314, India 5 School of Physics, University of Hyderabad, Hyderabad 500046, India 6 Cavendish Laboratory, Thin Film Magnetism group, Department of Physics, University of Cambridge, Cambridge CB 0HE, U.K. 7 Department of Botany, Shivaji University, Kolhapur 416004, India 8 Department of Biochemistry, The New College, Kolhapur 416012, India Direct functionalization strategy has been employed to modify the surface of the magnetic hollow spheres (MHS) with (3-aminopropyl)triethoxysilane (APTES) for controlled drug release. The MHS were prepared by the solvothermal method and characterized by X-ray diffraction, field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy, and vibrating sample magnetometer. The FE-SEM study shows that MHS have a size of ∼200 nm and are made up of smaller nanoparticles (NPs) having average size of ∼20–25 nm. MHS exhibits a superparamagnetic behavior with a saturation magnetization of 74 emu/g at room temperature. The direct functionalization of MHS with APTES provided an efficient loading of model anti- cancer drug Camptothecin (CPT). The drug release study performed at pH of 7.4 showed 30% of CPT release in a controlled way after 4 h. Index Terms—Functionalization, magnetic hollow spheres (MHS), magnetic nanoparticles (MNPs), targeted drug delivery. I. I NTRODUCTION A NUMBER of advanced drug delivery systems (DDS) have been developed to improve the therapeutic effi- cacy and bioavailability of poorly water-soluble drugs [1]–[6]. Presently, many micro and nanoscale organic and inorganic drug carriers such as micelles, liposomes, mesoporous par- ticles, polymers, metal and metal oxide nanoparticles (NPs) have been reported [3]–[9]. However, many of these systems have biocompatibility issues, related to the toxicity and strong interaction with serum proteins, which causes occasional rapid blood clearance and hepatic removal [10]. Among the variety of nanodrug carriers, magnetic NPs (MNPs) are most impor- tant due to their intrinsic magnetic properties at nanoscale, bet- ter stability in physiological fluids, and lower toxicity profile toward normal cells. The unique feature of MNPs is that they can be translocated at the target site by an external magnetic field, which can be employed for the targeted DDS [11]–[13]. Magnetic hollow spheres (MHS) can be the most promising potential candidate for the development of efficient DDS. The higher outer surface area along with the inner accessible voids within hollow spheres can provide higher loading capacity of the drug on the outer and inner surfaces of MHS [14]. Manuscript received March 10, 2017; revised April 26, 2017; accepted May 16, 2017. Date of publication May 29, 2017; date of current version October 24, 2017. Corresponding author: P. B. Patil (e-mail: prashantphy@ gmail.com). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TMAG.2017.2706949 To link the drug or any biological entity to MNPs, appro- priate surface modification of MNPs is required. The various polymer coatings such as polyethylene glycol [15]–[17], dex- tran [18]–[20], and chitosan [21], [22] have been routinely explored for surface modifications of MNPs. MNP-silica core– shell structure has also been widely used as a drug carrier sys- tem [1], [3]–[6], [21], [22]. However, such coating of MNPs with a nonmagnetic material may lead to decrease in its magnetic properties, limited drug storage capacity, and time- consuming synthesis protocols, which hinder them from being high-performance carriers in targeted DDS [1], [5], [18], [23]. (3-aminopropyl)triethoxysilane (APTES) is the most com- monly used alkoxysilane linker for surface modification of MNPs due to its terminal amino groups. Generally, to link APTES the silica-coated MNPs or mesoporous silica NPs have been used [24], [25]. We have adopted a strategy to directly functionalize MHS with APTES, which avoids the use of nonmagnetic coatings and retains its magnetization. The direct functionalization of APTES on MHS offers sev- eral advantages over silica-coated MNPs. Direct linking of APTES can weaken the interparticle magnetic interaction and prevent the particle agglomeration providing increased colloidal stability. It also provides amino functional groups, which can be used for the bonding of different bioactive complexes, drug or anti-body [26], [27]. Camptothecin (CPT) is a water-insoluble anti-tumor drug isolated from the orien- tal tree Camptotheca accuminata [28]. CPT is well known for its anti-cancerous activity against different human can- cers by inhibition of cellular enzyme deoxyribonuclic acid 0018-9464 © 2017 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information.