Preparation and in vitro Evaluation of Magnetic Microsphere-Methotrexate Conjugate Drug Delivery Systems

Abstract

Magnetic microsphere-methoxtrexate (MM-MTX) conjugates prepared by several different methods were analyzed for their suitability for in vivo use. MM-MTX were prepared by the following methods: (A) reaction of MTX with poly(ethylene glycol) 1500 (PEG) to form a poly(ethylene glycol)-methotrexate conjugate (PEGMTX) which was then added to a ferrous/ferric ion salt solution to give MM-MTX I; (B) reaction of ferrous/ferric ion salts with PEG to give a ferromagnetic polymer complex which was then coupled with MTX to give MM-MTX II; (C) MM-MTX IIIA were prepared by reacting MTX with amino-terminated magnetic microspheres, commercially available, in the presence of 1-ethyl-3,3-bis(methylamino)propylcarbodiimide (EDCI); (D) reaction of aminohexanol with di-tert-butyl dicarbonate to form an [N-(tert-butoxycarbonyl)amino]hexanol (t-Boc-AH), which was then coupled with MTX in the presence of 1,3-dicyclohexylcarbodiimide and 4-pyrrolidinopyridine to give a t-Boc-AH-MTX conjugate, which was then saturated with hydrogen chloride to give an aminohexanol-methotrexate (AH-MTX) conjugate. MM-MTX IIIB were then prepared by reacting AH-MTX with carboxyl-terminated magnetic microspheres, commercially available, in the presence of EDCI and 4-(dimethylamino)pyridine. The identity of MTX conjugates was confirmed using ultraviolet, infrared, and nuclear magnetic resonance spectroscopy. Drug content of the magnetic microsphere-methotrexate conjugates as determined by HPLC was 0.45% (w/w), 4.0% (w/w), and 6.3% (w/w) MTX for MM-MTX I, MM-MTX II, and MM-MTX IIIB, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Templated synthesis of gold–iron alloy nanoparticles using pulsed laser deposition

“…An inherent limitation of these iron oxide nanoparticle composites is that they have a relatively low magnetization and 3 Author to whom any correspondence should be addressed. will ultimately degrade due to the decomposition of magnetite to a nonmagnetic ferrite [20][21][22].…”

Gelatin-Methotrexate Conjugate Microspheres as a Potential Drug Delivery System

“…More free MTX was released from MCS‐L than from higher molar ratio MCS as shown in Figure 5. Devineni et al29 found a similar result with three types of magnetic MCS–MTX conjugate drug delivery systems prepared from different conjugation procedures. The MCS with the highest drug load (6.3 ± 2.1% as compared to 4.0 ± 0.9 and 0.45 ± 0.2% (w/w)) had a markedly slower release in rat plasma and brain homogenate.…”

“…The design and resulting properties of MCS delivery systems will substantially influence their release characteristics. Only a few reports have described MCS in which the drug was covalently bound to the polymer carrier 28–30. Mitra et al encapsulated doxorubicin–dextran conjugates inside chitosan MCS 31.…”

Bio-effects of non-ionizing electromagnetic fields in context of cancer therapy

“…It has been demonstrated that the utilizing of nanoparticles in combination with EMF allows an effective destruction of malignant cells and provides a platform for drug and gene delivery (15,(86)(87)(88)(89)(90)(91). Various types of nano-carriers such as magnetic microsphere-methotrexate conjugates (92), micro-particles containing metallic iron and activated carbon (93), and magnetoliposomes have been proposed (94). Although all of them vary in size, structure, magnetic and thermal properties the application of magnetic nanoparticles mostly relies on generation of heat upon exposure to EMF, thus providing a basis for developing thermal bio-effects and release of loaded substances to the tissues.…”