Alendronic Acid as Ionic Liquid: New Perspective on Osteosarcoma

Abstract

Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.

Boosting Antimicrobial Activity of Ciprofloxacin by Functionalization of Mesoporous Silica Nanoparticles

“…Recently, an interesting class of compounds that combines active pharmaceutical ingredients (APIs) with biocompatible counter-ions, such as organic salts and ionic liquids (OSILs)—API-OSILs—has been reported as a promising alternative to improve the original drug properties in terms of crystallinity, stability, solubility, permeability and delivery [ 1 , 2 ]. In our research group, we have been involved in the preparation and characterization of API-OSILs from β-lactam [ 3 , 4 , 5 , 6 , 7 ], fluoroquinolone [ 7 , 8 , 9 ], antibiotics, NSAIDs (ibuprofen [ 7 , 10 ], naproxen [ 7 ]) and bone antiresorptive agents (zoledronic [ 11 ] and alendronic [ 12 ] drugs). More specifically, our works on API-OSILs based on fluoroquinolone drugs, namely ciprofloxacin and norfloxacin, focused on their combination as organic cations with methanesulfonate (Mes), gluconate (Glu) and glycolate (Gly) as anions [ 8 ], or acting as organic anions with organic cations such as pyridinium, ammonium and N -methylimidazolium moieties [ 9 ].…”

pH-Responsive Nanostructures Based on Surface Active Fatty Acid-Protic Ionic Liquids for Imiquimod Delivery in Skin Cancer Topical Therapy

“…The range of potential applications of ILs span from alternative solvents for organic reactions [ 29 ] to dissolution media for biopolymers [ 30 ], and from lubricants [ 31 ] to electrolyte for batteries [ 32 ], to mention a few. Undeniably, in the last few years, the biomedical and pharmaceutical industry has turned increasing attention towards ILs due to their yet unexplored potential as bioactive agents or to their ability to solubilize and stabilize drugs [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Furthermore, the cation and/or anion amphiphilic nature can be finely balanced to trigger the self-assembling behavior of ILs [ 40 , 41 , 42 , 43 , 44 ].…”

Antimicrobial Activities of Highly Bioavailable Organic Salts and Ionic Liquids from Fluoroquinolones

“…For more than a decade, active pharmaceutical ingredients as organic salts and ionic liquids (API-OSILs) have risen in academia as an alternative formulation for low bioavailable drugs [9][10][11][12]. This third generation of ionic liquids [9] consists on the combination of APIs as cations or anions with organic counterions, thereby inducing distinctive physicochemical properties over the original drugs and reduced toxicity to healthy cells, thus rendering a potentially enhanced pharmaceutical activity in comparison to the API [13][14][15][16][17][18][19][20][21][22][23][24][25]. Our works involving the preparation of API-OSILs from, e.g., β-lactam (ampicillin [18][19][20][21], penicillin [22] and amoxicillin [22]) and fluoroquinolone [18,23] antibiotics, NSAIDs (ibuprofen [17,18], naproxen [18]), bone antiresorptive agents (zoledronic [24] and alendronic [25] acids), among others, have shown that the combination of an API, either as a cation or as an anion, with suitable biocompatible counter-ions can increase the water solubility of the parent drug and even change its biological effect [10,17,[23][24][25][26][27][28].…”