Folate‐intercalated layered double hydroxide as a vehicle for cyclophosphamide, a non‐ionic anti‐cancer drug

Abstract

Layered double hydroxides (LDH) are matrices with interlayer anions that can be exchanged with several types of organic or inorganic anions. Due to the anion-exchange capability, hundreds of new materials have been prepared in the past two decades. Conversely, attempts to intercalate neutral molecules (and increase the range of applications) have been achieved by expanding the interlayer space with longchain surfactants, thus allowing to exclusively retain highly hydrophobic molecules. This work describes a folate-intercalated LDH structure, where folate pillars are capable of forming both hydrogen bonds and hydrophobic interactions with neutral molecules. Infrared spectroscopy and X-ray diffraction data indicated that imidazole, urea and cyclophosphamide were successfully intercalated. This evidence increases the opportunity to prepare more novel materials with neutral molecules in LDH. The cyclophosphamide-LDH product here obtained represents a remarkable example of an LDH-based vehicle for a non-ionic anti-cancer drug used in current chemotherapies.1. Introduction: Layered double hydroxides (LDH) are synthetic layered compounds widely known for their positively charged layers as a result of the isomorphic substitution of divalent cations located in octahedral sites of brucite-like layers by trivalent cations [1]. The positive charge is neutralised by interlayer anions, which can be exchanged with a large number of anions. This anion-exchange property is the most remarkable feature of these structures [2, 3] because even organic anions can be inserted between the layers by the exchange process to produce new hybrid materials such as gene and drug vehicles [4,5], polymer flame retardants [6], enzyme supports [7,8] or nutraceutical and cosmeceutical carriers [9, 10]. Due to the ease of intercalating different types of anions into LDH, hundreds of scientific articles are published every year. Unusual cases of neutral molecules intercalated in LDH have been reported with ribose and curcubituril [11,12] and attempts to improve this intercalation involves pre-expansion of LDH with long chain anions. Examples of this is the intercalation of iphosphamide into a pre-expanded LDH with dodecylsulphate (DDS); the intercalation of ultraviolet (UV)-absorbers after expansion of the interlayer space with DDS or dodecylbenzenesulphonate [13]; and the intercalation of curcubituril into a pre-expanded LDH with DDS [12].This strategy has been limited to increase the size of interlayer galleries with long chain hydrophobic anions (surfactants) and consequently, the neutral species intercalated further required a high hydrophobic character. In fact, we have observed our own experiments that urea (a highly polar molecule) does not intercalate into surfactant pre-expanded LDH.On the other hand, considering that folic acid, by itself, can retain aromatic molecules like anthracene due to an attraction with π bonds [14], the present Letter reports the use of a pre-expanded LDH structure with folate anions where the aromatic rings allow r...

Tartrazine-intercalated Zn–Al layered double hydroxide as a pigment for gel nail polish: synthesis and characterisation

“…For instance, stabilizing [20] or activating [21,22] anions can be introduced into the LDH structure. A promising application for LDH is as nano-containers for special anions, such as drugs [23,24], dyes [25], sensor [26], corrosion inhibitors [27], dietary supplements [28], food additives [29,30], etc. In practical terms, LDH is an ionic constructors with three main components [31]: "host" metal cation, "guest" metal cation, and intercalated anion.…”

Determination of the applicability of Zn­Al layered double hydroxide, intercalated by food dye Orange Yellow S, as a cosmetic pigment

“…Stabilizing [20] or activating anions [21,22] can be added to the composition of LDH. It is promising to use LDH as a nanocontainer for special anions, for example, drugs [23,24], dye anions [25], anions for sensors [26], corrosion inhibitors [27], biologically active additives [28], food additives [29,30] and others.…”

The determination of synthesis conditions and color properties of pigments based on layered double hydroxides with Co as a guest cation

“…Stabilizing [30] or activating anions [31,32] are most often added to the LDH composition. It is promising to use LDH as a nano container for special anions, for example, drugs [33,34], dye anions [35], anions for sensors [36], corrosion inhibitors [37], biologically active additives [38], food additives [39,40] and others.…”